Patent Publication Number: US-2003224418-A1

Title: Genes and polymorphisms associated with cardiovascular disease and their use

Description:
RELATED APPLICATIONS  
     [0001] This application is a divisional application of copending U.S. patent application Ser. No. 09/802,640, filed Mar. 9, 2001, to Andreas Braun, Aruna Bansal and Patrick Kleyn, entitled “GENES AND POLYMORPHISMS ASSOCIATED WITH CARDIOVASCULAR DISEASE AND THEIR USE.” The benefit of priority to this application is claimed and the subject matter of the application is incorporated herein in its entirety. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The field of the invention involves genes and polymorphisms of these genes that are associated with development of cardiovascular disease. Methods that use polymorphic markers for prognosticating, profiling drug response and drug discovery are provided.  
       BACKGROUND OF THE INVENTION  
       [0003] Diseases in all organisms have a genetic component, whether inherited or resulting from the body&#39;s response to environmental stresses, such as viruses and toxins. The ultimate goal of ongoing genomic research is to use this information to develop new ways to identify, treat and potentially cure these diseases. The first step has been to screen disease tissue and identify genomic changes at the level of individual samples. The identification of these “disease” markers has then fueled the development and commercialization of diagnostic tests that detect these errant genes or polymorphisms. With the increasing numbers of genetic markers, including single nucleotide polymorphisms (SNPs), microsatellites, tandem repeats, newly mapped introns and exons, the challenge to the medical and pharmaceutical communities is to identify genotypes which not only identify the disease but also follow the progression of the disease and are predictive of an organism&#39;s response to treatment.  
       [0004] Polymorphisms  
       [0005] Polymorphisms have been known since 1901 with the identification of blood types. In the 1950&#39;s they were identified on the level of proteins using large population genetic studies. In the 1980&#39;s and 1990&#39;s many of the known protein polymorphisms were correlated with genetic loci on genomic DNA. For example, the gene dose of the apolipoprotein E type 4 allele was correlated with the risk of Alzheimer&#39;s disease in late onset families (see, e.g., Corder et al. (1993)  Science  261: 921-923; mutation in blood coagulation factor V was associated with resistance to activated protein C (see, e.g., Bertina et al. (1994)  Nature  369:64-67); resistance to HIV-1 infection has been shown in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene (see, e.g., Samson et al. (1996)  Nature  382:722-725); and a hypermutable tract in antigen presenting cells (APC, such as macrophages), has been identified in familial colorectal cancer in individuals of Ashkenzi jewish background (see, e.g., Laken et al. (1997)  Nature Genet.  17:79-83). There may be more than three million polymorphic sites in the human genome. Many have been identified, but not yet characterized or mapped or associated with a disease. Polymorphisms of the genome can lead to altered gene function, protein function or mRNA instability. To identify hose polymorphisms that have clinical relevance is the goal of a world-wide scientific effort. Discovery of such polymorphisms will have a fundamental impact on the identification and development of diagnostics and drug discovery.  
       [0006] Single Nucleotide Polymorphisms (SNPs)  
       [0007] Much of the focus of genomics has been in the identification of SNPs, which are important for a variety of reasons. They allow indirect testing (association of haplotypes) and direct testing (functional variants). They are the most abundant and stable genetic markers. Common diseases are best explained by common genetic alterations, and the natural variation in the human population aids in understanding disease, therapy and environmental interactions.  
       [0008] The organization of SNPs in the primary sequence of a gene into one of the limited number of combinations that exist as units of inheritance is termed a haplotype. Each haplotype therefore contains significantly more information than individual unorganized polymorphisms and provides an accurate measurement of the genomic variation in the two chromosomes of an individual. While it is well-established that many diseases are associated with specific variation in gene sequences and there are examples in which individual polymorphisms act as genetic markers for a particular phenotype, in other cases an individual polymorphism may be found in a variety of genomic backgrounds and therefore shows no definitive coupling between the polymorphism and the phenotype. In these instances, the observed haplotype and its frequency of occurrence in various genotypes will provide a better genetic marker for the phenotype.  
       [0009] Although risk factors for the development of cardiovascular disease are known, such as high serum cholesterol levels and low serum high density lipoprotein (HDL) levels, the genetic basis for the manifestation of these phenotypes remains unknown. An understanding of the genes that are responsible for controlling cholesterol and HDL levels, along with useful genetic markers and mutations in these genes that affect these phenotypes, will allow for detection of a predisposition for these risk factors and/or cardiovascular disease and the development of therapeutics to modulate such alterations. Therefore, it is an object herein to provide methods for using polymorphic markers to detect a predisposition to the manifestation of high serum cholesterol, low serum HDL and cardiovascular disease. The ultimate goals are the elucidation of pathological pathways, developing new diagnostic assays, determining genetic profiles for positive responses to therapeutic drugs, identifying new potential drug targets and identifying new drug candidates.  
       SUMMARY OF THE INVENTION  
       [0010] A database of twins was screened for individuals which exhibit high or low levels of serum cholesterol or HDL. Using a full genome scanning approach, SNPs present in DNA samples from these individuals were examined for alleles that associate with either high levels of cholesterol or low levels of HDL. This lead to the discovery of the association of the cytochrome C oxidase subunit VIb (COX6B) gene and the N-acetylglucosaminyl transferase component GPI-1 (GPI-1) gene with these risks factors for developing cardiovascular disease. Specifically, a previously undetermined association of an allelic variant at nucleotide 86 of the COX6B gene and high serum cholesterol levels has been discovered. In addition, it has been discovered that an allelic variant at nucleotide 2577 of the GPI-1 gene is associated with low serum HDL levels. There was no previously known association between these two genes and risk factors related to cardiovascular disease.  
       [0011] Methods are provided for detecting the presence or absence of at least one allelic variant associated with high cholesterol, low HDL and/or cardiovascular disease by detecting the presence or absence of at least one allelic variant of the COX6B gene or the GPI-1 gene, individually or in combination with one or more allelic variants of other genes associated with cardiovascular disease.  
       [0012] Also provided are methods for indicating a predisposition to manifesting high serum cholesterol, low serum HDL and/or cardiovascular disease based on detecting the presence or absence of at least one allelic variant of the COX6B or GPI-1 genes, alone or in combination with one or more allelic variants of other genes associated with cardiovascular disease. These methods, referred to as haplotyping, are based on assaying more than one polymorphism of the COX6B and/or GPI-1 genes. One or more polymorphisms of other genes associated with cardiovascular disease may also be assayed at the same time. A collection of allelic variants of one or more genes may be more informative than a single allelic variant of any one gene. A single polymorphism of a collection of polymorphisms present in the COX6B and/or GPI-1 genes and in other genes associated with cardiovascular disease may be assayed individually or the collection may be assayed simultaneously using a multiplex assay method.  
       [0013] Also provided are microarrays comprising a probe selected from among an oligonucleotide complementary to a polymorphic region surrounding position 86 of the sense strand of the COX6B gene coding sequence; an oligonucleotide complementary to a polymorphic region surrounding the position of the antisense strand of COX6B corresponding to position 86 of the sense strand of the COX6B gene coding sequence; an oligonucleotide complementary to a polymorphic region surrounding position 2577 of the sense strand of the GPI-1 gene; and an oligonucleotide complementary to a polymorphic region surrounding the position of the antisense strand of GPI-1 corresponding to position 2577 of the sense strand of the GPI-1 gene. Microarrays are well known and can be made, for example, using methods set forth in U.S. Pat. Nos. 5,837,832; 5,858,659; 6,043,136; 6,043,031 and 6,156,501.  
       [0014] Further provided are methods of utilizing allelic variants of the COX6B or GPI-1 gene individually or together with one or more allelic variants of other genes associated with cardiovascular disease to predict a subject&#39;s response to a biologically active agent that modulates serum cholesterol, serum HDL, or a cardiovascular drug.  
       [0015] Also provided are methods to screen candidate biologically active agents for modulation of cholesterol, HDL or other factors associated with cardiovascular disease. These methods utilize cells or transgenic animals containing one or more allelic variants of the COX6B gene and/or the GPI-1 gene alone or in combination with allelic variants of one or more other genes associated with cardiovascular disease. Such animals should exhibit high cholesterol, low HDL or other known phenotypes associated with cardiovascular disease. Also, provided are methods to construct transgenic animals that are useful as models for cardiovascular disease by using one or more allelic variants of the COX6B gene and/or the GPI-1 gene alone or in combination with allelic variants of one or more other genes associated with cardiovascular disease.  
       [0016] Further provided are combinations of probes and primers and kits for predicting a predisposition to high serum cholesterol, low HDL levels and/or cardiovascular disease. In particular, combinations and kits comprise probes or primers which are capable of hybridizing adjacent to or at polymorphic regions of the COX6B and/or GPI-1 gene. The combinations and kits can also contain probes or primers which are capable of hybridizing adjacent to or at polymorphic regions of other genes associated with cardiovascular disease. The kits also optionally contain instructions for carrying out assays, interpreting results and for aiding in diagnosing a subject as having a predisposition towards developing high serum cholesterol, low HDL levels and/or cardiovascular disease. Combinations and kits are also provided for predicting a subject&#39;s response to a therapeutic agent directed toward modulating cholesterol, HDL, or another phenotype associated with cardiovascular disease. Such combinations and kits comprise probes or primers as described above.  
       [0017] In particular for the methods, combinations, kits and arrays described above, the polymorphisms are SNPs. The detection or identification is of a T nucleotide at position 86 of the sense strand of the COX6B gene coding sequence or the detection or identification of an A nucleotide at the corresponding position in the antisense strand of the COX6B gene coding sequence. Also embodied is the detection or identification of an A nucleotide at position 2577 of the sense strand of the GPI-1 gene or the detection or identification of a T nucleotide at the corresponding position in the antisense strand of the GPI-1 gene. In addition to the SNPs discussed above, other polymorphisms of the COX6B and GPI-1 genes can be assayed for association with high cholesterol or low HDL, respectively, and utilized as disclosed above.  
       [0018] Other genes containing allelic variants associated with high serum cholesterol, low HDL and/or cardiovascular disease, include, but are not limited to: cholesterol ester transfer protein, plasma (CETP); apolipoprotein A-IV (APO A4); apolipoprotein A-I (APO A1); apolipoprotein E (APO E); apolipoprotein B (APO B); apolipoprotein C-III (APO C3); a gene encoding lipoprotein lipase (LPL); ATP-binding cassette transporter (ABC 1); paraoxonase 1 (PON 1); paraoxonase 2 (PON 2); 5,10-methylenetetrahydrofolate r reductase (MTHFR); a gene encoding hepatic lipase, E-selectin, G protein beta 3 subunit, and angiotensin II type 1 receptor gene.  
       [0019] The detection of the presence or absence of an allelic variant can utilize, but are not limited to, methods such as allele specific hybridization, primer specific extension, oligonucleotide ligation assay, restriction enzyme site analysis and single-stranded conformation polymorphism analysis.  
       [0020] In particular, primers utilized in primer specific extension hybridize adjacent to nucleotide 86 of the COX6B gene or nucleotide 2577 of the GPI-1 gene or the corresponding positions on the antisense strand (numbers refer to GenBank sequences, see pages 15-17). A primer can be extended in the presence of at least one dideoxynucleotide, particularly ddG, or two dideoxynucleotides, particularly ddG and ddC. Preferably, detection of extension products is by mass spectrometry. Detection of allelic variants can also involve signal moieties such as radioisotopes, enzymes, antigens, antibodies, spectrophotometric reagents, chemiluminescent reagents, fluorescent reagents and other light producing reagents.  
       [0021] Other probes and primers useful for the detection of allelic variants include those which hybridize at or adjacent to the SNPs described in Tables 1-3 and specifically those that comprise SEQ ID NOs.: 5, 10, 43, 48, 53, 58, 63, 68, 73, 78, 83, 88, 93, 98, 103, 108, 113, and 118. 
     
    
    
     DESCRIPTION OF THE DRAWINGS  
     [0022]FIG. 1 depicts the allelic frequency and genotype for pools and individually determined samples of blood from individuals having low cholesterol levels and those with high cholesterol levels.  
     [0023]FIG. 2 depicts the allelic frequency and genotype for pools and individually determined samples of blood from individuals having high HDL levels and those with low HDL levels. 
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS  
     [0024] A. Definitions  
     [0025] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents, patent applications and publications referred to throughout the disclosure herein are, unless noted otherwise, incorporated by reference in their entirety. In the event that there are a plurality of definitions for terms herein, those in this section prevail.  
     [0026] As used herein, sequencing refers to the process of determining a nucleotide sequence and can be performed using any method known to those of skill in the art. For example, if a polymorphism is identified or known, and it is desired to assess its frequency or presence in nucleic acid samples taken from the subjects that comprise the database, the region of interest from the samples can be isolated, such as by PCR or restriction fragments, hybridization or other suitable method known to those of skill in the art, and sequenced. For purposes herein, sequencing analysis is preferably effected using mass spectrometry (see, e.g., U.S. Pat. Nos. 5,547,835, 5,622,824, 5,851,765, and 5,928,906). Nucleic acids can also be sequenced by hybridization (see, e.g., U.S. Pat. Nos. 5,503,980, 5,631,134, 5,795,714) and including analysis by mass spectrometry (see, U.S. application Ser. Nos. 08/419,994 and 09/395,409). Alternatively, sequencing may be performed using other known methods, such as set forth in U.S. Pat. Nos. 5,525,464; 5,695,940; 5,834,189; 5,869,242; 5,876,934; 5,908,755; 5,912,118; 5,952,174; 5,976,802; 5,981,186; 5,998,143; 6,004,744; 6,017,702; 6,018,041; 6,025,136; 6,046,005; 6,087,095; 6,117,634, 6,013,431, WO 98/30883; WO 98/56954; WO 99/09218; WO/00/58519, and the others.  
     [0027] As used herein, “polymorphism” refers to the coexistence of more than one form of a gene or portion thereof. A portion of a gene of which there are at least two different forms, i.e., two different nucleotide sequences, is referred to as a “polymorphic region of a gene”. A polymorphic region can be a single nucleotide, the identity of which differs in different alleles. A polymorphic region can also be several nucleotides in length.  
     [0028] As used herein, “polymorphic gene” refers to a gene having at least one polymorphic region.  
     [0029] As used herein, “allele”, which is used interchangeably herein with “allelic variant” refers to alternative forms of a gene or portions thereof. Alleles occupy the same locus or position on homologous chromosomes. When a subject has two identical alleles of a gene, the subject is said to be homozygous for the gene or allele. When a subject has two different alleles of a gene, the subject is said to be heterozygous for the gene. Alleles of a specific gene can differ from each other in a single nucleotide, or several nucleotides, and can include substitutions, deletions, and insertions of nucleotides. An allele of a gene can also be a form of a gene containing a mutation.  
     [0030] As used herein, the term “subject” refers to mammals and in particular human beings.  
     [0031] As used herein, the term “gene” or “recombinant gene” refers to a nucleic acid molecule comprising an open reading frame and including at least one exon and (optionally) at least one intron sequence. A gene can be either RNA or DNA. Genes may include regions preceding and following the coding region (leader and trailer).  
     [0032] As used herein, “intron” refers to a DNA sequence present in a given gene which is spliced out during mRNA maturation.  
     [0033] As used herein, the term “coding sequence” refers to that portion of a gene that encodes an amino acid sequence of a protein.  
     [0034] As used herein, the term “sense strand” refers to that strand of a double-stranded nucleic acid molecule that encodes the sequence of the mRNA that encodes the amino acid sequence encoded by the double-stranded nucleic acid molecule.  
     [0035] As used herein, the term “antisense strand” refers to that strand of a double-stranded nucleic acid molecule that is the complement of the sequence of the mRNA that encodes the amino acid sequence encoded by the double-stranded nucleic acid molecule.  
     [0036] As used herein, a DNA or nucleic acid homolog refers to a nucleic acid that includes a preselected conserved nucleotide sequence. By the term “substantially homologous” is meant having at least 80%, preferably at least 90%, most preferably at least 95% homology therewith or a less percentage of homology or identity and conserved biological activity or function.  
     [0037] Regarding hybridization, as used herein, stringency conditions to achieve specific hybridization refer to the washing conditions for removing the non-specific probes or primers and conditions that are equivalent to either high, medium, or low stringency as described below:  
                                                      1) high stringency:   0.1 × SSPE, 0.1% SDS, 65° C.           2) medium stringency:   0.2 × SSPE, 0.1% SDS, 50° C.           3) low stringency:   1.0 × SSPE, 0.1% SDS, 50° C.                      
 
     [0038] It is understood that equivalent stringencies may be achieved using alternative buffers, salts and temperatures.  
     [0039] As used herein, “heterologous DNA” is DNA that encodes RNA and proteins that are not normally produced in vivo by the cell in which it is expressed or that mediates or encodes mediators that alter expression of endogenous DNA by affecting transcription, translation, or other regulatable biochemical processes or is not present in the exact orientation or position as the counterpart DNA in a wildtype cell. Heterologous DNA may also be referred to as foreign DNA. Any DNA that one of skill in the art would recognize or consider as heterologous or foreign to the cell in which is expressed is herein encompassed by heterologous DNA. Examples of heterologous DNA include, but are not limited to, DNA that encodes traceable marker proteins, such as a protein that confers drug resistance, DNA that encodes therapeutically effective substances, such as anti-cancer agents, enzymes and hormones, and DNA that encodes other types of proteins, such as antibodies. Antibodies that are encoded by heterologous DNA may be secreted or expressed on the surface of the cell in which the heterologous DNA has been introduced.  
     [0040] As used herein, a “promoter region” refers to the portion of DNA of a gene that controls transcription of the DNA to which it is operatively linked. The promoter region includes specific sequences of DNA that are sufficient for RNA polymerase recognition, binding and transcription initiation. This portion of the promoter region is referred to as the promoter. In addition, the promoter region includes sequences that modulate this recognition, binding and transcription initiation activity of the RNA polymerase. These sequences may be cis acting or may be responsive to trans acting factors. Promoters, depending upon the nature of the regulation, may be constitutive or regulated.  
     [0041] As used herein, the phrase “operatively linked” generally means the sequences or segments have been covalently joined into one piece of DNA, whether in single or double stranded form, whereby control or regulatory sequences on one segment control or permit expression or replication or other such control of other segments. The two segments are not necessarily contiguous. For gene expression a DNA sequence and a regulatory sequence(s) are connected in such a way to control or permit gene expression when the appropriate molecular, e.g., transcriptional activator proteins, are bound to the regulatory sequence(s).  
     [0042] As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of preferred vector is an episome, i.e., a nucleic acid capable of extra-chromosomal replication. Preferred vectors are those capable of autonomous replication and/or expression of nucleic acids to which they are linked. Vectors capable of directing the expression of genes to which they are operatively linked are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of “plasmids” which refer generally to circular double stranded DNA loops which, in their vector form are not bound to the chromosome. “Plasmid” and “vector” are used interchangeably as the plasmid is the most commonly used form of vector. Also included are other forms of expression vectors that serve equivalent functions and that become known in the art subsequently hereto.  
     [0043] As used herein, “indicating” or “determining” means that the presence or absence of an allelic variant may be one of many factors that are considered when a subject&#39;s predisposition to a disease or disorder is evaluated. Thus a predisposition to a disease or disorder is not necessarily conclusively determined by only ascertaining the presence or absence of one or more allelic variants, but the presence of one of more of such variants is among an number of factors considered.  
     [0044] As used herein, “predisposition to develop a disease or disorder” means that a subject having a particular genotype and/or haplotype has a higher likelihood than one not having such a genotype and/or haplotype for developing a particular disease or disorder.  
     [0045] As used herein, “transgenic animal” refers to any animal, preferably a non-human animal, e.g. a mammal, bird or an amphibian, in which one or more of the cells of the animal contain heterologous nucleic acid introduced by way of human intervention, such as by transgenic techniques well known in the art. The nucleic acid is introduced into the cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by microinjection or by infection with a recombinant virus. The term genetic manipulation does not include classical cross-breeding, or in vitro fertilization, but rather is directed to the introduction of a recombinant DNA molecule. This molecule may be integrated within a chromosome, or it may be extrachromosomally replicating DNA. In the typical transgenic animals described herein, the transgene causes cells to express a recombinant form of a protein. However, transgenic animals in which the recombinant gene is silent are also contemplated, as for example, using the FLP or CRE recombinase dependent constructs. Moreover, “transgenic animal” also includes those recombinant animals in which gene disruption of one or more genes is caused by human intervention, including both recombination and antisense techniques.  
     [0046] As used herein, “associated” refers to coincidence with the development or manifestation of a disease, condition or phenotype. Association may be due to, but is not limited to, genes responsible for housekeeping functions, those that are part of a pathway that is involved in a specific disease, condition or phenotype and those that indirectly contribute to the manifestation of a disease, condition or phenotype.  
     [0047] As used herein, “high serum cholesterol” refers to a level of serum cholesterol that is greater than that considered to be in the normal range for a given age in a population, e.g., about 5.25 mmoles/L or greater, i.e., approximately one standard deviation or more away from the age-adjusted mean.  
     [0048] As used herein, “low serum HDL” refers to a level of serum HDL that is less than that considered to be in the normal range for a given age in a population, e.g. about 1.11 mmoles/L or less, i.e., approximately one standard deviation or more away from the age-adjusted mean.  
     [0049] As used herein, “cardiovascular disease” refers to any manifestation of or predisposition to cardiovascular disease including, but not limited to, coronary artery disease and myocardial infarction. Included in predisposition is the manifestation of risks factors such as high serum cholesterol levels and low serum HDL levels.  
     [0050] As used herein, “target nucleic acid” refers to a nucleic acid molecule which contains all or a portion of a polymorphic region of a gene of interest.  
     [0051] As used herein, “signal moiety” refers to any moiety that allows for the detection of a nucleic acid molecule. Included are moieties covalently attached to nucleic acids and those that are not.  
     [0052] As used herein, “biologically active agent that modulates serum cholesterol” refers to any drug, small molecule, nucleic acid (sense and antisense), protein, peptide, lipid, carbohydrate etc. or combination thereof, that exhibits some effect directly or indirectly on the cholesterol measured in a subject&#39;s serum.  
     [0053] As used herein, “biologically active agent that modulates serum HDL” refers to any drug, small molecule, nucleic acid (sense and antisense), protein, peptide, lipid, carbohydrate etc. or combination thereof that exhibits some effect directly or indirectly on the HDL measured in a subject&#39;s serum.  
     [0054] As used herein, “expression and/or activity” refers to the level of transcription or translation of the COX6B or GPI-1 gene, mRNA stability, protein stability or biological activity.  
     [0055] As used herein, “cardiovascular drug” refers to a drug used to treat cardiovascular disease or a risk factor for the disease, either prophylactically or after a risk factor or disease condition has developed. Cardiovascular drugs include those drugs used to lower serum cholesterol and those used to alter the level of serum HDL.  
     [0056] As used herein, “combining” refers to contacting the biologically active agent with a cell or animal such that the agent is introduced into the cell or animal. For a cell any method that results in an agent traversing the plasma membrane is useful. For an animal any of the standard routes of administration of an agent, e.g. oral, rectal, transmucosal, intestinal, intravenous, intraperitoneal, intraventricular, subcutaneous, intramuscular, etc., can be utilized.  
     [0057] As used herein,“positive response” refers to improving or ameliorating at least one symptom or detectable characteristic of a disease or condition, e.g., lowering serum cholesterol levels or raising serum HDL levels.  
     [0058] As used herein, “biological sample” refers to any cell type or tissue of a subject from which nucleic acid, particularly DNA, can be obtained.  
     [0059] As used herein, “array” refers to a collection of three or more items, such a collection of immobilized nucleic acid probes arranged on a solid substrate, such as silica, polymeric materials or glass.  
     [0060] As used herein, a composition refers to any mixture. It may be a solution, a suspension, liquid, powder, a paste, aqueous, non-aqueous or any combination thereof.  
     [0061] As used herein, a combination refers to any association between two or among more items.  
     [0062] As used herein, “kit” refers to a package that contains a combination, such as one or more primers or probes used to amplify or detect polymorphic regions of genes associated with cardiovascular disease, optionally including instructions and/or reagents for their use.  
     [0063] As used herein “specifically hybridizes” refers to hybridization of a probe or primer only to a target sequence preferentially to a non-target sequence. Those of skill in the art are familiar with parameters that affect hybridization; such as temperature, probe or primer length and composition, buffer composition and salt concentration and can readily adjust these parameters to achieve specific hybridization of a nucleic acid to a target sequence.  
     [0064] As used herein “nucleic acid” refers to polynucleotides such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The term should also be understood to include, as equivalents, derivatives, variants and analogs of either RNA or DNA made from nucleotide analogs, single (sense or antisense) and double-stranded polynucleotides. Deoxyribonucleotides include deoxyadenosine, deoxycytidine, deoxyguanosine and deoxythymidine. For RNA, the uracil base is uridine.  
     [0065] As used herein, “mass spectrometry” encompasses any suitable mass spectrometric format known to those of skill in the art. Such formats include, but are not limited to, Matrix-Assisted Laser Desorption/Ionization, Time-of-Flight (MALDI-TOF), Electrospray (ES), IR-MALDI (see, e.g., published International PCT Application No. 99/57318 and U.S. Pat. No. 5,118,937) Ion Cyclotron Resonance (ICR), Fourier Transform and combinations thereof. MALDI, particular UV and IR, are among the preferred formats.  
     [0066] B. Cytochrome c Oxidase VIb Gene  
     [0067] Cytochrome c oxidase (COX) is a mitochondrial enzyme complex integrated in the inner membrane. It transfers electrons from cytochrome to molecular oxygen in the terminal reaction of the respiratory chain in eukaryotic cells. COX contains of three large subunits encoded by the mitochondrial genome and 10 other subunits, encoded by nuclear genes. The three subunits encoded by mitochondrial genome are responsible for the catalytic activity. The cytochrome c oxidase subunit VIb (COX6B) is one of the nuclear gene products. The function of the nuclear encoded subunits is unknown. One proposed role is in the regulation of catalytic activity; specifically the rate of electron transport and stoichiometry of proton pumping. Other proposed roles are not directly related to electron transport and include energy-dependent calcium uptake and protein import by the mitochondrion. Proteolytic removal of subunits VIa and VIb has been associated with loss of calcium transport in reconstituted vesicles. Steady-state levels of the COX6B transcript are different in different tissues (Taanman et al., Gene (1990), 93:285).  
     [0068] The COX6B gene is generically used to include the human COX6B gene and its homologs from rat, mouse, guinea pig, etc.  
     [0069] Several single nucleotide polymorphism have been identified in the human COX6B gene. One of these is located at position 86 and is a C to T transversion which is manifested as a silent mutation in the coding region, ACC to ACT (threonine to threonine)(SEQ ID NO.: 2). Although this is a silent mutation at the amino acid level, it may represent an alteration that changes codon usage, or it may effect mRNA stability or it may be in linkage disequilibrium with a non-silent change. Other known single nucleotide polymorphisms of the COX6B gene include, but are not limited to, those listed in Table 1.  
                           TABLE 1                       Gene   GenBank Accession No.   SNP   SNP Location                                                COX6B   NM_001863   C/T   86       (SEQ ID NO.: 1)       A/G   60               A/T   324               A/T   123                  
 
     [0070] Based on methods disclosed herein and those used in the art, one of skill would be able to utilize all the SNPs described and find additional polymorphic regions of the COX6B gene to determine whether allelic variants of these regions are associated with high cholesterol levels and cardiovascular disease.  
     [0071] C. GPI-1 Gene  
     [0072] Glycosylphosphatidylinositol (GPI) functions to anchor various eukaryotic proteins to membranes and is essential for their surface expression. Thus, a defect in GPI anchor synthesis affects various functions of cell, tissues and organs. Biosynthesis of glycosylphosphatidylinositol (GPI) is initiated by the transfer of N-acetylglucosamine (GIcNAc) from UDP-GIcNAc to phosphatidylinositol (PI) and is catalyzed by a GIcNAc transferase, GPI-GIcNAc transferase (GPI-GnT). Four mammalian gene products form a protein complex that is responsible for this enzyme activity (PIG-A, PIG-H, PIG-C and GPI-1). PIG-A, PIG-H, PIG-C are required for the first step in GPI anchor biosynthesis; GPI-1 is not. Stabilization of the enzyme complex, rather than participation in GIcNAc transfer, has been suggested as a possible role for GPI-1 (Watanabe et al. EMBO (1998) 17: 877).  
     [0073] The GPI-1 gene is generically used to include the human GPI-1 gene and its homologs from rat, mouse, guinea pig, etc.  
     [0074] A polymorphism has been identified at position 2577 of the human GPI-1 gene. This is a G to A transversion. This SNP is located in the 3′ untranslated region of the mRNA, and does not affect protein structure, but may affect mRNA stability or may be in linkage disequilibrium with a non-silent change. Other known single nucleotide polymorphisms of the GPI-1 gene include, but are not limited to, those listed in Table 2.  
                           TABLE 2                           GenBank               Gene   Accession No.   SNP   SNP Location                  GPI-1   NM_004204   C/T   2829       (SEQ ID NOS.: 6, 7)       A/G   2577               C/T   2519               C/T   2289               C/T   1938               C/G   1563               A/G/C/T   2664               A/G   2656               A/C/T   2167               G/C/A   2166                  
 
     [0075] Based on methods disclosed herein and those used in the art, one of skill would be able to use all the described SNPs and find additional polymorphic regions of the GPI-1 gene to determine whether allelic variants of these regions are associated with low levels of HDL and cardiovascular disease.  
     [0076] D. Other Genes and Polymorphism Associated with Cardiovascular Disease  
     [0077] Many other genes and polymorphisms contained within them have been associated with risks factors for cardiovascular disease (aberrations in lipid metabolism; specifically high levels of serum cholesterol and low levels of HDL, etc.) and/or the clinical phenotypes of atherosclerosis and cardiovascular disease. Table 3 presents a list of some of these genes and some associated polymorphisms (SNPs): cholesterol ester transfer protein, plasma (CETP); apolipoprotein A-IV (APO A4); apolipoprotein A-I (APO A1); apolipoprotein E (APO E); apolipoprotein B (APO B); apolipoprotein C-III (APO C3); a gene encoding lipoprotein lipase (LPL); ATP-binding cassette transporter (ABC 1); paraoxonase 1 (PON 1); paraoxonase 2 (PON 2); 5,10-methylenetetrahydrofolate r reductase (MTHFR); a gene encoding hepatic lipase (LIPC); E-selectin; G protein beta 3 subunit and angiotensin II type 1 receptor gene. The SNP locations are based on the GenBank sequence. Table 3 is not meant to be exhaustive, as one of skill in the art based on the disclosure would be able to readily use other known polymorphisms in these and other genes, new polymorphisms discovered in previously identified genes and newly identified genes and polymorphisms in the methods and compositions disclosed herein.  
                           TABLE 3                           GenBank       SNP       Gene   Accession No.   SNP   Location                                                CETP   NM_000078   C/A   991       (SEQ ID NOS.: 11, 12)       C/T   196               A/G   1586               A/G   1394               A/G   1439               C/G   1297               C/T   766               G/A   1131               G/A   1696       LPL   NM_000237   A/G   1127       (SEQ ID NOS.: 13, 14)       A/C   3447               C/T   1973               C/T   3343               G/A   2851               C/T   3272               A/T   2428               T/C   2743               G/A   1453               C/A   3449               G/A   1282               G/A   579               A/C   1338               A/G/T/C   2416-2426               A/G   2427               C/T   1302               G/A   609               G/C   1595               G/A   1309               C/T   2454               C/T   2988               G/A   280               G/A   1036       APO A4   NM_000482   G/T   1122       (SEQ ID NOS.: 15, 16)       G/C   1033               G/A   1002               C/T   960               C/T   894               G/A   554               G/A   950               T/C   336               G/A   334               C/T   330               A/G   201               A/G   16               A/T   1213       APO E   NM_000041   C/T   448       (SEQ ID NOS.: 17, 18)       G/A   448       (mRNA)       C/T   586               C/T   197               C/T   540       Hepatic Lipase   NM_000236   C/G   680       (SEQ ID NOS.: 19, 20)       G/A   1374               G/A   701               C/A   1492               A/G   648               G/C   729               G/A   340               G/T   522       PON 1   NM_000446   A/T   172       (SEQ ID NOS.: 21, 22)       A/G   584               G/C   190       PON 2   XM_004947   C/G   475       (SEQ ID NOS.: 23, 24)       C/G   964       APO C3   NM_000040   C/T   148       (SEQ ID NOS.: 25, 26)       T/A   471               G/C   386               G/T   417               T/A   495       ABC 1   XM_005567   G/A   8591       (SEQ ID NOS.: 27, 28)       APO A1   NM_000039   C/G   770       (SEQ ID NOS.: 29, 30)       G/A   656               C/G   589               C/G   414               A/T   430               C/T   708               C/T   221               T/G   223               C/T   597               A/G   340               G/C   690       APO B   NM_000384   A/G/C/T   13141       (SEQ ID NOS.: 31, 32)       A/G/C/T   12669               C/T   11323               G/C   10422               A/C   10408               C/G   10083               C/T   7064               C/T   6666               C/T   1980               C/G   5751               C/T   7673               C/A/G/T   8344               G/C/T/A   4393               A/C/T/G   5894               A/T   12019               C/T   11973               G/C/T/A   7065               C/G   947               C/G   7331               A/G   7221               G/C   6402               G/C   3780               C/G   1661               A/T   8167               C/A   8126               C/T   421               C/T   1981               G/A   12510               G/C   12937       APO B (con&#39;t)       G/A   11042               C/T   2834               A/G   5869               A/G   11962               C/G   4439               G/A   7824               G/A   13569               G/A   9489               G/A   2325               G/A   10259               C/G   14       MTHFR   NM_005957   G/A   5442       (SEQ ID NOS.: 33, 34)       A/G   5113               A/G   5113               A/G   5110               A/G   5102               A/C/T   5097               A/C/T   5097               C/T   5079               C/T   5079               T/C   5071               T/C   5071               T/C   5051               G/A   5012               C/A   5000               A/G   4998               A/G   4994               A/G   4994               A/G   4994               C/T   4991               C/T   4991               C/T   4991               A/G   4986               A/G   4986               A/G   4986               C/T   4985               T/A   4982               T/G   4981               T/C   4981               T/C   4981       MTHFR (con&#39;t)       G/C/A   4967               G/A   4963               A/G   4962               G/C/T   4962               A/C/G/T   4961               A/C/T   4961               A/C   4961               A/C   4961               A/C/T   4960               T/C   4938               T/C   4937               T/C   4933               G/C/T   4933               C/T   4929               C/T   4929               T/A/G   4929               A/G   4928               G/C   4928               C/G   4927               G/A   4923               C/T   4919               A/T/G   4913               C/T   4912               A/T   4903               C/T   4902               A/G   4900               G/A   4898               G/T   4898               C/T   4897               G/T   4894               T/C/G   4836               C/T   3862               C/T   4922               C/T   4959               T/C   4981               A/G   4994               A/G   5044               T/C   5051               G/C   5066               C/T   5079       MTHFR (con&#39;t)       C/A/G   5085               C/T   5092               A/G   5103               A/G   5113               C/T   1021       E-Selectin   NM_000450   G/A   3484       (SEQ ID NOS.: 35, 36)       G/A   3093               T/G   2939               T/C   2902               C/T   1937               C/T   1916               C/T   1839               C/T   1805               C/T   1518               G/C   1377               C/T   1376               G/A   999               T/C   857               A/C   561               C/G   506               A/G   392               G/T   98       G protein β3 subunit   NM_002075   C/T   1828       (SEQ ID NOS.: 37, 38)       C/T   1546               G/T   1431               G/A   1231               C/T   1230       Angiotensin II type 1   NM_00686   G/A   1453       receptor gene       C/G   968       (SEQ ID NOS.: 39, 40)       G/C   966               T/C   941               G/A   894               T/C   659                  
 
     [0078] Assays to identify the nucleotide present at the polymorphic site include those described herein and all others known to those who practice the art.  
     [0079] For some of the SNPs described above, there are provided a description of the MassEXTEND™ reaction components that can be utilized to determine the allelic variant that is present. Included are the forward and reverse primers used for amplification. Also included are the MassEXTEND™ primer used in the primer extension reaction and the extended MassEXTEND™ primers for each allele. MassEXTEND™ reactions are carried out and the products analyzed as described in Examples 2 and 3.  
     [0080] CETP  
                                  Position 991 (C/A)                   PCR primers:               Forward:   ACTGCCTGATAACCATGCTG   (SEQ ID NO.: 41)               Reverse:   ATACTTACACACCAGGAGGG   (SEQ ID NO.: 42)               MassEXTENDTM Primer:   ATGCCTGCTCCAAAGGCAC   (SEQ ID NO.: 43)               Primer Mass:   5757.8               Extended Primer-Allele C:   ATGCCTGCTCCAAAGGCACC   (SEQ ID NO.: 44)               Extended Primer Mass:   6030.9               Extended Primer-Allele A:   ATGCCTGCTCCAAAGGCACAT   (SEQ ID NO.: 45)               Extended Primer Mass:   6359.2               Position 196 (CIT)               PCR primers:               Forward:   TACTTCTGGTTCTCTGAGCG   (SEQ ID NO.: 46)               Reverse:   ACTCACCTTGAACTCGTCTC   (SEQ ID NO.: 47)               MassEXTEND ™ Primer:   TGGTTCTCTGAGCGAGTCTT   (SEQ ID NO.: 48)               Primer Mass:   6130               Extended Primer-Allele C:   TGGTTCTCTGAGCGAGTCTTC   (SEQ ID NO.: 49)               Extended Primer Mass:   6707.4               Extended Primer-Allele T:   TGGTTCTCTGAGCGAGTCTTTC   (SEQ ID NO.: 50)               Extended Primer Mass:   6333.1               Position 1586 (AIG)               POR primers:               Forward:   TGCAGATGGACTTTGGCTTC   (SEQ ID NO.: 51)               Reverse:   TGCTTGCCTTCTGCTACAAG   (SEQ ID NO.: 52)               MassEXTENDTM Primer:   CTTCCCTGAGCACCTGCTG   (SEQ ID NO.: 53)               Primer Mass:   5715.7               Extended Primer-Allele G:   CTTCCCTGAGCACCTGCTGGT   (SEQ ID NO.: 54)               Extended Primer Mass:   6333.1               Extended Primer-Allele A:   CTTCCCTGAGCACCTGCTGA   (SEQ ID NO.: 55)               Extended Primer Mass:   601 2.9               APOA4               Position 1122 (GIT)               POR primers:               Forward:   AACAGCTCAGGACGAAACTG   (SEQ ID NO.: 56)               Reverse:   AGAAGGAGTTGACCTTGTCC   (SEQ ID NO.: 57)               MassEXTEND ™ Primer:   GGAAGCTCAAGTGGCCTTC   (SEQ ID NO.: 5)8)               Primer Mass:   5828.8               Extended Primer-Allele G:   GGAAGCTCAAGTGGCCTTCC   (SEQ ID NO.: 59)               Extended Primer Mass:   6102.0               Extended Primer-Allele T:   GGAAGCTCAAGTGGCCTTCAAC   (SEQ ID NO.: 60)               Extended Primer Mass:   6728.4               Position 1033 (GIC)               PCR primers:               Forward:   AAGTCACTGGCAGAGCTGG   (SEQ ID NO.: 61)               Reverse:   GCACCAGGGCTTTGTTGAAG   (SEQ ID NO.: 62)               MassEXTEND ™ Primer:   TTTTCCCCGTAGGGCTCCA   (SEQ ID NO.: 63)               Primer Mass:   5730.7               Extended Primer-Allele G:   TTTTCCCCGTAGGGCTCCAC   (SEQ ID NO.: 64)               Extended Primer Mass:   6003.9               Extended Primer-Allele C:   TTTTCCCCGTAGGGCTCCAGC   (SEQ ID NO.: 65)               Extended Primer Mass:   6333.1               Position 1002 (G/A)               PCR primers:               Forward:   TGCAGAAGTCACTGGCAGAG   (SEQ ID NO.: 66)               Reverse:   GTTGAAGTTTTCCCCGTAGG   (SEQ ID NO.: 67)               MassEXTEND ™ Primer:   ACTCCTCCACCTGCTGGTC   (SEQ ID NO.: 68)               Primer Mass:   5675.7               Extended Primer-Allele G:   ACTCCTCCACCTGCTGGTCC   (SEQ ID NO.: 69)               Extended Primer Mass:   5948.9               Extended Primer-Allele A:   ACTCCTCCACCTGCTGGTCTA   (SEQ ID NO.: 70)               Extended Primer Mass:   6277.1               Position 960 (CIT)               PCR primers:               Forward:   AGGACGTGCGTGGCAACCTG   (SEQ ID NO.: 71)               Reverse:   AGCTGTGCCAGTGACTTCTG   (SEQ ID NO.: 72)               MassEXTEND ™ Primer:   GTGACTTCTGCAGCCCCTC   (SEQ ID NO.: 73)               Primer Mass:   571 5.7               Extended Primer-Allele T:   GTGACTTCTGCAGCCCCTCA   (SEQ ID NO.: 74)               Extended Primer Mass:   601 2.9               Extended Primer-Allele C:   GTGACTTCTGGAGCCCCTCGGT   (SEQ ID NO.: 75)               Extended Primer Mass:   6662.3               Position 894 (CIT)               PCR primers:               Forward:   CCTGACCTTCCAGATGAAG   (SEQ ID NO.: 76)               Reverse:   TCAGGTTGCCACGCACGTC   (SEQ ID NO.: 77)               MassEXTEND ™ Primer:   CAGGATCTCGGCCAGTGC   (SEQ ID NO.: 78)               Primer Mass:   5500.6               Extended Primer-Allele C:   CAGGATCTCGGCCAGTGCC   (SEQ ID NO.: 79)               Extended Primer Mass:   5773.8               Extended Primer-Allele T:   CAGGATCTCGGCCAGTGCTG   (SEQ ID NO.: 80)               Extended Primer Mass:   61 18.0               Position 554 (G/A)               PCR primers:               Forward:   ACCTGCGAGAGCTTCAGCAG   (SEQ ID NO.: 81)               Reverse:   TCTCCATGCGCTGTGCGTAG   (SEQ ID NO.: 82)               MassEXTEND ™ Primer:   AGCTGCGCACCCAGGTCA   (SEQ ID NO.: 83)               Primer Mass:   5469.6               Extended Primer-Allele A:   AGCTGCGCACCCAGGTCAA   (SEQ ID NO.: 84)               Extended Primer Mass:   5766.8               Extended Primer-Allele G:   AGCTGCGCACCCAGGTCAGC   (SEQ ID NO.: 85)               Extended Primer Mass:   6072.0               APOE               Position 448 (CIT)               PCR primers:               Forward:   TGTCCAAGGAGCTGCAGGC   (SEQ ID NO.: 86)               Reverse:   CTTACGCAGCTTGCGCAGGT   (SEQ ID NO.: 87)               MassEXTEND ™ Primer:   GCGGAGATGGAGGACGTG   (SEQ ID NO.: 88)               Primer Mass:   5629.7               Extended Primer-Allele C:   GCGGACATGGAGGACGTGC   (SEQ ID NO.: 89)               Extended Primer Mass:   5902.8               Extended Primer-Allele T:   GCGGACATGGAGGACGTGTG   (SEQ ID NO.: 90)               Extended Primer Mass:   6247.1               LPL               Position 1127 (A/G)               PCR primers:               Forward:   GTTGTAGAAAGAACCGCTGC   (SEQ ID NO.: 91)               Reverse:   GAGAACGAGTCTTCAGGTAC   (SEQ ID NO.: 92)               MassEXTEND ™ Primer:   ACAATCTGGGCTATGAGATCA   (SEQ ID NO.: 93)               Primer Mass:   6454.2               Extended Primer-Allele A:   ACAATCTGGGCTATGAGATCAA   (SEQ ID NO.: 94)               Extended Primer Mass:   6751 .4               Extended Primer-Allele G:   ACAATCTGGGCTATGAGATCAGT   (SEQ ID NO.: 95)               Extended Primer Mass:   7071 .6               Position 3447 (A/C)               PCR primers:               Forward:   GACTCTACACTGCATGTCTC   (SEQ ID NO.: 96)               Reverse:   ACCCTTCTGAAAAGGAGAGG   (SEQ ID NO.: 97)               MassEXTENDTM Primer:   GAGGAGAGACAAGGCAGATA   (SEQ ID NO.: 98)               Primer Mass:   6273.1               Extended Primer-Allele A:   GAGGAGAGACAAGGCAGATAT   (SEQ ID NO.: 99)               Extended Primer Mass:   6561.3               Extended Primer-Allele C:   GAGGAGAGACAAGGCAGATAGT   (SEQ ID NO.: 100)               Extended Primer Mass:   6890.5               Position 1973 (C/TI               PCR primers:               Forward:   AAAGGTTCAGTTGCTGCTGC   (SEQ ID NO.: 101)               Reverse:   GCTGGGGAAGGTCTAATAAC   (SEQ ID NO.: 102)               MassEXTENDTM Primer:   GTTGCTGCTGCCTCGAATG   (SEQ ID NO.: 103)               Primer Mass:   5770.7               Extended Primer-Allele C:   GTTGCTGCTGCCTCGAATCC   (SEQ ID NO.: 104)               Extended Primer Mass:   6043.9               Extended Primer-Allele T:   GTTGCTGCTGCCTCGAATCTG   (SEQ ID NO.: 105)               Extended Primer Mass:   6388.2               LIPC               Position 680 (CIG)               PCR primers:               Forward:   CGTCTTTCTCCAGATGATGC   (SEQ ID NO.: 106)               Reverse:   AGTGTCCTATGGGCTGTTTG   (SEQ ID NO.: 107)               MassEXTEND ™ Primer:   GGATGCCATTCATACCTTTAC   (SEQ ID NO.: 108)               Primer Mass:   6556.1               Extended Primer-Allele C:   GGATGCCATTCATACCTTTACC   (SEQ ID NO.: 109)               Extended Primer Mass:   6629.3               Extended Primer-Allele G:   GGATGCCATTCATACCTTTACGC   (SEQ ID NO.: 110)               Extended Primer Mass:   6958.5               Position 1374 (GIA)               PCR primers:               Forward:   TGGGAAAACAGTGCAGTGTG   (SEQ ID NO.: 111)               Reverse:   TGATCGTCTTCAGAACGAGG   (SEQ ID NO.: 112)               MassEXTEND ™ Primer:   CCAGACCATCATCCCATGGA   (SEQ ID NO.: 113)               Primer Mass:   6030.9               Extended Primer-Allele A:   CCAGACCATCATCCCATGGAA   (SEQ ID NO.: 114)               Extended Primer Mass:   6328.1               Extended Primer-Allele G:   CCAGACCATCATCCCATGGAGC   (SEQ ID NO.: 115)               Extended Primer Mass:   6633.3               Position 701 (G/A)               PCR primers:               Forward:   CAGCAATCGTCTTTCTCCAG   (SEQ ID NO.: 116)               Reverse:   TCCTATGGGCTGTTTGATGC   (SEQ ID NO.: 117)               MassEXTEND ™ Primer:   GTCTTTCTCCAGATGATGCCA   (SEQ ID NO.: 118)               Primer Mass:   6372.2               Extended Primer-Allele A:   GTCTTTCTCCAGATGATGCCAA   (SEQ ID NO.: 119)               Extended Primer Mass:   6669.4               Extended Primer-Allele G:   GTCTTTCTCCAGATGATGCCAGT   (SEQ ID NO.: 120)               Extended Primer Mass:   6989.6                  
 
     [0081] E. Databases  
     [0082] Databases for determining an association between polymorphic regions of genes and intermediate and clinical phenotypes, comprise biological samples (e.g., blood) which provide a source of nucleic acid and clinical data covering diseases (e.g., age, sex, ethnicity medical history and family medical history) from both individuals exhibiting the phenotype (intermediate phenotype (risk factor) or clinical phenotype (disease)) and those who do not. These databases include human population groups such as twins, diverse affected families, isolated founder populations and drug trial subjects. The quality and consistency of the clinical resources are of primary importance.  
     [0083] F. Association Studies  
     [0084] The examples set forth below utilized an extreme trait analysis to discover an association between an allelic variant of the COX6B gene and high cholesterol and an association between an allelic variant of the GPI-1 gene and low HDL. This analysis is based on comparing a pair of pools of DNA from individuals who exhibit respectively hypo or hypernormal levels of a biochemical trait (e.g., cholesterol or HDL) and individually examining SNPs for a difference in allelic frequency between the pools. An association is considered to be positive if a statistically significant value of at least 3.841 using a 1-degree-of-freedom chi-squared test of association, p=0.05, is obtained. Standard multiple testing corrections are applied if more than one SNP is considered at a time, i.e., multiple SNPs are tested during the same study. Although not always required, it may be necessary to further examine the frequency of allelic variants in other populations, including those exhibiting normal levels of the given trait.  
     [0085] For a qualitative trait (e.g., hypertension) association studies are based on determining the occurrence of certain alleles in a given population of diseased vs. healthy individuals.  
     [0086] Allelic variants of COX6B, GPI-1 and other genes found to associate with high cholesterol, low HDL and/or cardiovascular disease can represent useful markers for indicating a predisposition for developing a risk factor for cardiovascular disease. These allelic variants may not necessarily represent functional variants affecting the expression, stability, or activity of the encoded protein product. Those of skill in the art would be able to determine which allelic variants are to be used, alone or in conjunction with other variants, only for indicating a predisposition for cardiovascular disease or for profiling of drug reactivity and for determining those which may be also useful for screening for potential therapeutics.  
     [0087] Any method used to determine association can be utilized to discover or confirm the association of other polymorphic regions in the COX6B gene, the GPI-1 gene or any other gene that may be associated with cardiovascular disease.  
     [0088] G. Detection of Polymorphisms  
     [0089] 1. Nucleic Acid Detection Method  
     [0090] Generally, these methods are based in sequence-specific polynucleotides, oligonucleotides, probes and primers. Any method known to those of skill in the art for detecting a specific nucleotide within a nucleic acid sequence or for determining the identity of a specific nucleotide in a nucleic acid sequence is applicable to the methods of determining the presence or absence of an allelic variant of a COX6B gene or GPI-1 gene or another gene associated with cardiovascular disease. Such methods include, but are not limited to, techniques utilizing nucleic acid hybridization of sequence-specific probes, nucleic acid sequencing, selective amplification, analysis of restriction enzyme digests of the nucleic acid, cleavage of mismatched heteroduplexes of nucleic acid and probe, alterations of electrophoretic mobility, primer specific extension, oligonucleotide ligation assay and single-stranded conformation polymorphism analysis. In particular, primer extension reactions that specifically terminate by incorporating a dideoxynucleotide are useful for detection. Several such general nucleic acid detection assays are described in U.S. Pat. No. 6,030,778.  
     [0091] a. Primer Extension-Based Methods  
     [0092] Several primer extension-based methods for determining the identity of a particular nucleotide in a nucleic acid sequence have been reported (see, e.g., PCT Application No. PCT/US96/03651 (WO96/29431), PCT Application No. PCT/US97/20444 (WO 98/20019), PCT Application No. PCT/US91/00046 (WO91/13075), and U.S. Pat. No. 5,856,092). In general, a primer is prepared that specifically hybridizes adjacent to a polymorphic site in a particular nucleic acid sequence. The primer is then extended in the presence of one or more dideoxynucleotides, typically with at least one of the dideoxynucleotides being the complement of the nucleotide that is polymorphic at the site. The primer and/or the dideoxynucleotides may be labeled to facilitate a determination of primer extension and identity of the extended nucleotide.  
     [0093] In a preferred method, primer extension and/or the identity of the extended nucleotide(s) are determined by mass spectrometry (see, e.g., PCT Application Nos. PCT/US96/03651 (WO96/29431) and PCT/US97/20444 (WO 98/20019)).  
     [0094] b. Polymorphism-Specific Probe Hybridization  
     [0095] A preferred detection method is allele specific hybridization using probes overlapping the polymorphic site and having about 5, 10, 15, 20, 25, or 30 nucleotides around the polymorphic region. The probes can contain naturally occurring or modified nucleotides (see U.S. Pat. No. 6,156,501). For example, oligonucleotide probes may be prepared in which the known polymorphic nucleotide is placed centrally (allele-specific probes) and then hybridized to target DNA under conditions which permit hybridization only if a perfect match is found (Saiki et al. (1986) Nature 324: 163; Saiki et al. (1989) Proc. Natl Acad. Sci USA 86: 6230; and Wallace et al. (1979) Nucl. Acids Res. 6: 3543). Such allele specific oligonucleotide hybridization techniques may be used for the simultaneous detection of several nucleotide changes in different polymorphic regions. For example, oligonucleotides having nucleotide sequences of specific allelic variants are attached to a hybridizing membrane and this membrane is then hybridized with labeled sample nucleic acid. Analysis of the hybridization signal will then reveal the identity of the nucleotides of the sample nucleic acid. In a preferred embodiment, several probes capable of hybridizing specifically to allelic variants are attached to a solid phase support, e.g., a “chip”. Oligonucleotides can be bound to a solid support by a variety of processes, including lithography. For example a chip can hold up to 250,000 oligonucleotides (GeneChip, Affymetrix, Santa Clara, Calif.). Mutation detection analysis using these chips comprising oligonucleotides, also termed “DNA probe arrays” is described e.g., in Cronin et al. (1996) Human Mutation 7: 244 and in Kozal et al. (1996) Nature Medicine 2: 753. In one embodiment, a chip includes all the allelic variants of at least one polymorphic region of a gene. The solid phase support is then contacted with a test nucleic acid and hybridization to the specific probes is detected. Accordingly, the identity of numerous allelic variants of one or more genes can be identified in a simple hybridization experiment.  
     [0096] C. Nucleic Acid Amplification-Based Methods  
     [0097] In other detection methods, it is necessary to first amplify at least a portion of a COX6B gene, GPI-1 gene or another gene associated with cardiovascular disease prior to identifying the allelic variant. Amplification can be performed, e.g., by PCR and/or LCR, according to methods known in the art. In one embodiment, genomic DNA of a cell is exposed to two PCR primers and amplification is performed for a number of cycles sufficient to produce the required amount of amplified DNA. In preferred embodiments, the primers are located between 1 50 and 350 base pairs apart.  
     [0098] Alternative amplification methods include: self sustained sequence replication (Guatelli, J. C. et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87: 1874-1878); transcriptional amplification system (Kwoh, D. Y. et al. (1989) Proc. Natl. Acad. Sci. U.S.A. 86: 1173-1177), Q-Beta Replicase (Lizardi, P. M. et al. (1988) Bio/Technology 6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.  
     [0099] Alternatively, allele specific amplification technology, which depends on selective PCR amplification may be used in conjunction with the alleles provided herein. Oligonucleotides used as primers for specific amplification may carry the allelic variant of interest in the center of the molecule (so that amplification depends on differential hybridization) (Gibbs et al. (1989) Nucleic Acids Res. 17:2437-2448) or at the extreme 3′ end of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (Prossner (1993) Tibtech 11:238; Newton et al. (1989) Nucl. Acids Res. 17:2503). In addition it may be desirable to introduce a restriction site in the region of the mutation to create cleavage-based detection (Gasparini et al. (1992) Mol. Cell Probes 6:1).  
     [0100] d. Nucleic Acid Sequencing-Based Methods  
     [0101] In one embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence at least a portion of the COX6B gene, GPI-1 gene or other gene associated with cardiovascular disease and to detect allelic variants, e.g., mutations, by comparing the sequence of the sample sequence with the corresponding wild-type (control) sequence. Exemplary sequencing reactions include those based on techniques developed by Maxam and Gilbert (Proc. Natl. Acad. Sci. USA (1977) 74:560) or Sanger (Sanger et al. (1977) Proc. Natl. Acad. Sci 74:5463). It is also contemplated that any of a variety of automated sequencing procedures may be used when performing the subject assays (Biotechniques (1995) 19:448), including sequencing by mass spectrometry (see, for example, U.S. Pat. No. 5,547,835 and International PCT Application No. WO 94/16101, entitled DNA Sequencing by Mass Spectrometry by H. Koster; U.S. Pat. No. 5,547,835 and International PCT Application No. WO 94/21822, entitled “DNA Sequencing by Mass Spectrometry Via Exonuclease Degradation” by H. Koster), and U.S. Pat. No. 5,605,798 and International Patent Application No. PCT/US96/03651 entitled DNA Diagnostics Based on Mass Spectrometry by H. Koster; Cohen et al. (1996) Adv Chromatogr 36:127-162; and Griffin et al. (1993) Appl Biochem Biotechnol 38:147-159). It will be evident to one skilled in the art that, for certain embodiments, the occurrence of only one, two or three of the nucleic acid bases need be determined in the sequencing reaction. For instance, A-track sequencing or an equivalent, e.g., where only one nucleotide is detected, can be carried out. Other sequencing methods are disclosed, e.g., in U.S. Pat. No. 5,580,732 entitled “Method of DNA sequencing employing a mixed DNA-polymer chain probe” and U.S. Pat. No. 5,571,676 entitled “Method for mismatch-directed in vitro DNA sequencing”.  
     [0102] e. Restriction Enzyme Digest Analysis  
     [0103] In some cases, the presence of a specific allele in nucleic acid, particularly DNA, from a subject can be shown by restriction enzyme analysis. For example, a specific nucleotide polymorphism can result in a nucleotide sequence containing a restriction site which is absent from the nucleotide sequence of another allelic variant.  
     [0104] f. Mismatch Cleavage  
     [0105] Protection from cleavage agents, such as, but not limited to, a nuclease, hydroxylamine or osmium tetroxide and with piperidine, can be used to detect mismatched bases in RNA/RNA DNA/DNA, or RNA/DNA heteroduplexes (Myers, et al. (1985) Science 230:1242). In general, the technique of “mismatch cleavage” starts by providing heteroduplexes formed by hybridizing a control nucleic acid, which is optionally labeled, e.g., RNA or DNA, comprising a nucleotide sequence of an allelic variant with a sample nucleic acid, e.g, RNA or DNA, obtained from a tissue sample. The double-stranded duplexes are treated with an agent, which cleaves single-stranded regions of the duplex such as duplexes formed based on basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digest the mismatched regions.  
     [0106] In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine whether the control and sample nucleic acids have an identical nucleotide sequence or in which nucleotides they differ (see, for example, Cotton et al. (1988) Proc. Natl Acad Sci USA 85: 4397; Saleeba et al. (1992) Methods Enzymol. 217: 286-295). The control or sample nucleic acid is labeled for detection.  
     [0107] g. Electrophoretic Mobility Alterations  
     [0108] In other embodiments, alteration in electrophoretic mobility is used to identify the type of allelic variant in the COX6B gene, GPI-1 gene or other gene associated with cardiovascular disease. For example, single-strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids (Orita et al. (1989) Proc. Natl. Acad. Sci. USA 86:2766, see also Cotton (1993) Mutat Res 285:125-144; and Hayashi (1992) Genet Anal Tech Appl 9:73-79). Single-stranded DNA fragments of sample and control nucleic acids are denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In another preferred embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility (Keen et al. (1991) Trends Genet 7:5).  
     [0109] h. Polyacrylamide Gel Electrophoresis  
     [0110] In yet another embodiment, the identity of an allelic variant of a polymorphic region in the COX6B gene, GPI-1 gene or other gene associated with cardiovascular disease is obtained by analyzing the movement of a nucleic acid comprising the polymorphic region in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE) (Myers et al. (1985) Nature 313:495). When DGGE is used as the method of analysis, DNA will be modified to ensure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing agent gradient to identify differences in the mobility of control and sample DNA (Rosenbaum and Reissner (1987) Biophys Chem 265:1275).  
     [0111] i. Oligonucleotide Ligation Assay (OLA)  
     [0112] In another embodiment, identification of the allelic variant is carried out using an oligonucleotide ligation assay (OLA), as described, e.g., in U.S. Pat. No. 4,998,617 and in Landegren, U. et al., Science 241:1077-1080 (1988). The OLA protocol uses two oligonucleotides which are designed to be capable of hybridizing to abutting sequences of a single strand of a target. One of the oligonucleotides is linked to a separation marker, e.g,. biotinylated, and the other is detectably labeled. If the precise complementary sequence is found in a target molecule, the oligonucleotides will hybridize such that their termini abut, and create a ligation substrate. Ligation then permits the labeled oligonucleotide to be recovered using avidin, or another biotin ligand. Nickerson, D. A. et al. have described a nucleic acid detection assay that combines attributes of PCR and OLA (Nickerson, D. A. et al., Proc. Natl. Acad. Sci. (U.S.A.) 87:8923-8927 (1990). In this method, PCR is used to achieve the exponential amplification of target DNA, which is then detected using OLA.  
     [0113] Several techniques based on this OLA method have been developed and can be used to detect specific allelic variants of a polymorphic region of a gene. For example, U.S. Pat. No. 5,593,826 discloses an OLA using an oligonucleotide having 3′ -amino group and a 5′-phosphorylated oligonucleotide to form a conjugate having a phosphoramidate linkage. In another variation of OLA described in Tobe et al. (1996) Nucl. Acids Res. 24: 3728), OLA combined with PCR permits typing of two alleles in a single microtiter well. By marking each of the allele-specific primers with a unique hapten, i.e. digoxigenin and fluorescein, each OLA reaction can be detected by using hapten specific antibodies that are labeled with different enzyme reporters, alkaline phosphatase or horseradish peroxidase. This system permits the detection of the two alleles using a high throughput format that leads to the production of two different colors.  
     [0114] j. SNP Detection Methods  
     [0115] Also provided are methods for detecting single nucleotide polymorphisms. Because single nucleotide polymorphisms constitute sites of variation flanked by regions of invariant sequence, their analysis requires no more than the determination of the identity of the single nucleotide present at the site of variation and it is unnecessary to determine a complete gene sequence for each patient. Several methods have been developed to facilitate the analysis of such single nucleotide polymorphisms.  
     [0116] In one embodiment, the single base polymorphism can be detected by using a specialized exonuclease-resistant nucleotide, as disclosed, e.g., in Mundy, C. R. (U.S. Pat. No. 4,656,127). According to the method, a primer complementary to the allelic sequence immediately 3′ to the polymorphic site is permitted to hybridize to a target molecule obtained from a particular animal or human. If the polymorphic site on the target molecule contains a nucleotide that is complementary to the particular exonuclease-resistant nucleotide derivative present, then that derivative will be incorporated onto the end of the hybridized primer. Such incorporation renders the primer resistant to exonuclease, and thereby permits its detection. Since the identity of the exonuclease-resistant derivative of the sample is known, a finding that the primer has become resistant to exonucleases reveals that the nucleotide present in the polymorphic site of the target molecule was complementary to that of the nucleotide derivative used in the reaction. This method has the advantage that it does not require the determination of large amounts of extraneous sequence data.  
     [0117] In another embodiment, a solution-based method for determining the identity of the nucleotide of a polymorphic site is employed (Cohen, D. et al. (French Patent 2,650,840; PCT Application No. WO91/02087)). As in the Mundy method of U.S. Pat. No. 4,656,127, a primer is employed that is complementary to allelic sequences immediately 3′ to a polymorphic site. The method determines the identity of the nucleotide of that site using labeled dideoxynucleotide derivatives, which, if complementary to the nucleotide of the polymorphic site will become incorporated onto the terminus of the primer.  
     [0118] k. Genetic Bit Analysis  
     [0119] An alternative method, known as Genetic Bit Analysis or GBA™ is described by Goelet, et al. (U.S. Pat. No. 6,004,744, PCT Application No. 92/15712). The method of Goelet, et al. uses mixtures of labeled terminators and a primer that is complementary to the sequence 3′ to a polymorphic site. The labeled terminator that is incorporated is thus determined by, and complementary to, the nucleotide present in the polymorphic site of the target molecule being evaluated. In contrast to the method of Cohen et al. (French Patent 2,650,840; PCT Application No. WO91/02087), the method of Goelet, et al. is preferably a heterogeneous phase assay, in which the primer or the target molecule is immobilized to a solid phase.  
     [0120] I. Other Primer-Guided Nucleotide Incorporation Procedures  
     [0121] Other primer-guided nucleotide incorporation procedures for assaying polymorphic sites in DNA have been described (Komher, J. S. et al., Nucl. Acids Res. 17:7779-7784 (1989); Sokolov, B. P., Nucl. Acids Res. 18:3671 (1990); Syvanen, A. C., et al., Genomics 8:684-692 (1990), Kuppuswamy, M. N. et al., Proc. Natl. Acad. Sci. (U.S.A.) 88:1143-1147 (1991); Prezant, T. R. et al., Hum. Mutat. 1:159-164 (1992); Ugozzoli, L. et al., GATA 9:107-112 (1992); Nyren, P. et al., Anal. Biochem. 208:171-175 (1993)). These methods differ from GBA™ in that they all rely on the incorporation of labeled deoxynucleotides to discriminate between bases at a polymorphic site. In such a format, since the signal is proportional to the number of deoxynucleotides incorporated, polymorphisms that occur in runs of the same nucleotide can result in signals that are proportional to the length of the run (Syvanen, A. C., et al., Amer. J. Hum. Genet. 52:46-59 (1993)).  
     [0122] For determining the identity of the allelic variant of a polymorphic region located in the coding region of a gene, yet other methods than those described above can be used. For example, identification of an allelic variant which encodes a mutated protein can be performed by using an antibody specifically recognizing the mutant protein in, e.g., immunohistochemistry or immunoprecipitation. Binding assays are known in the art and involve, e.g., obtaining cells from a subject, and performing binding experiments with a labeled lipid, to determine whether binding to the mutated form of the protein differs from binding to the wild-type protein.  
     [0123] m. Molecular Structure Determination  
     [0124] If a polymorphic region is located in an exon, either in a coding or non-coding region of the gene, the identity of the allelic variant can be determined by determining the molecular structure of the mRNA, pre-mRNA, or cDNA. The molecular structure can be determined using any of the above described methods for determining the molecular structure of the genomic DNA, e.g., sequencing and SSCP.  
     [0125] n. Mass Spectrometric Methods  
     [0126] Nucleic acids can also be analyzed by detection methods and protocols, particularly those that rely on mass spectrometry (see, e.g., U.S. Pat. No. 5,605,798, allowed co-pending U.S. application Ser. No. 08/617,256, allowed co-pending U.S. application Ser. No. 08/744,481, U.S. application Ser. No. 08/990,851, International PCT Application No. WO 98/20019). These methods can be automated (see, e.g., co-pending U.S. application Ser. No. 09/285,481, which describes an automated process line). Preferred among the methods of analysis herein are those involving the primer oligo base extension (PROBE) reaction with mass spectrometry for detection (described herein and elsewhere, see e.g., U.S. application Ser. Nos. 08/617,256, 09/287,681, 09/287,682, 09/287,141 and 09/287,679, allowed co-pending U.S. application Ser. No. 08/744,481, International PCT Application No. PCT/US97/20444, published as International PCT Application No. WO 98/20019, and based upon U.S. application Ser. Nos. 08/744,481, 08/744,590, 08/746,036, 08/746,055, 08/786,988, 08/787,639, 08/933,792, 08/746,055, 08/786,988 and 08/787,639; see, also U.S. application Ser. No. 09/074,936, allowed U.S. application Ser. No. 08/787,639, and U.S. application Ser. Nos. 08/746,055 and 08/786,988, and published International PCT Application No. WO 98/20020).  
     [0127] A preferred format for performing the analyses is a chip based format in which the biopolymer is linked to a solid support, such as a silicon or silicon-coated substrate, preferably in the form of an array. More preferably, when analyses are performed using mass spectrometry, particularly MALDI, nanoliter volumes of sample are loaded on, such that the resulting spot is about, or smaller than, the size of the laser spot. It has been found that when this is achieved, the results from the mass spectrometric analysis are quantitative. The area under the peaks in the resulting mass spectra are proportional to concentration (when normalized and corrected for background). Methods for preparing and using such chips are described in allowed co-pending U.S. application Ser. No. 08/787,639, co-pending U.S. application Ser. Nos. 08/786,988, 09/364,774, 09/371,150 and 09/297,575; see, also U.S. application Ser. No. PCT/US97/20195, which published as International PCT Application No. WO 98/20020. Chips and kits for performing these analyses are commercially available from SEQUENOM under the trademark MassARRAY™. MassARRAY™ relies on the fidelity of the enzymatic primer extension reactions combined with the miniaturized array and MALDI-TOF (Matrix-Assisted Laser Desorption Ionization-Time of Flight) mass spectrometry to deliver results rapidly. It accurately distinguishes single base changes in the size of DNA fragments relating to genetic variants without tags.  
     [0128] Multiplex methods allow for the simultaneous detection of more than one polymorphic region in a particular gene or polymorphic regions in several genes. This is the preferred method for carrying out haplotype analysis of allelic variants of the COX6B and/or GPI-1 genes separately, or along with allelic variants of one or more other genes associated with cardiovascular disease.  
     [0129] Multiplexing can be achieved by several different methodologies. For example, several mutations can be simultaneously detected on one target sequence by employing corresponding detector (probe) molecules (e.g., oligonucleotides or oligonucleotide mimetics). The molecular weight differences between the detector oligonucleotides must be large enough so that simultaneous detection (multiplexing) is possible. This can be achieved either by the sequence itself (composition or length) or by the introduction of mass-modifying functionalities into the detector oligonucleotides (see below).  
     [0130] Mass modifying moieties can be attached, for instance, to either the 5′-end of the oligonucleotide, to the nucleobase (or bases), to the phosphate backbone, and to the 2′-position of the nucleoside (nucleosides) and/or to the terminal 3′-position. Examples of mass modifying moieties include, for example, a halogen, an azido, or of the type, XR, wherein X is a linking group and R is a mass-modifying functionality. The mass-modifying functionality can thus be used to introduce defined mass increments into the oligonucleotide molecule.  
     [0131] The mass-modifying functionality can be located at different positions within the nucleotide moiety (see, e.g., U.S. Pat. No. 5,547,835 and International PCT Application No. WO 94/21822). For example, the mass-modifying moiety, M, can be attached either to the nucleobase, (in case of the c 7 -deazanucleosides also to C-7), to the triphosphate group at the alpha phosphate or to the 2′-position of the sugar ring of the nucleoside triphosphate. Modifications introduced at the phosphodiester bond, such as with alpha-thio nucleoside triphosphates, have the advantage that these modifications do not interfere with accurate Watson-Crick base-pairing and additionally allow for the one-step post-synthetic site-specific modification of the complete nucleic acid molecule e.g., via alkylation reactions (see, e.g., Nakamaye et al. (1988) Nucl. Acids Res. 16:9947-59). Particularly preferred mass-modifying functionalities are boron-modified nucleic acids since they are better incorporated into nucleic acids by polymerases (see, e.g., Porter et al. (1995) Biochemistry 34:11963-11969; Hasan et al. (1996) Nucleic Acids Res. 24:2150-2157; Li et al. (1995) Nucl. Acids Res. 23:4495-4501).  
     [0132] Furthermore, the mass-modifying functionality can be added so as to affect chain termination, such as by attaching it to the 3′-position of the sugar ring in the nucleoside triphosphate. For those skilled in the art, it is clear that many combinations can be used in the methods provided herein. In the same way, those skilled in the art will recognize that chain-elongating nucleoside triphosphates can also be mass-modified in a similar fashion with numerous variations and combinations in functionality and attachment positions.  
     [0133] For example, without being bound to any particular theory, the mass-modification can be introduced for X in XR as well as using oligo-/polyethylene glycol derivatives for R. The mass-modifying increment (m) in this case is 44, i.e. five different mass-modified species can be generated by just changing m from 0 to 4 thus adding mass units of 45 (m=0), 89 (m=1), 133 (m=2), 177 (m=3) and 221 (m=4) to the nucleic acid molecule (e.g., detector oligonucleotide (D) or the nucleoside triphosphates, respectively). The oligo/polyethylene glycols can also be monoalkylated by a lower alkyl such as, but are not limited to, methyl, ethyl, propyl, isopropyl and t-butyl. Other chemistries can be used in the mass-modified compounds (see, e.g., those described in Oligonucleotides and Analogues, A Practical Approach, F. Eckstein, editor, IRL Press, Oxford, 1991).  
     [0134] In yet another embodiment, various mass-modifying functionalities, R, other than oligo/polyethylene glycols, can be selected and attached via appropriate linking chemistries, X. A simple mass-modification can be achieved by substituting H for halogens, such as F, Cl, Br and/or I, or pseudohalogens such as CN, SCN, NCS, or by using different alkyl, aryl or aralkyl moieties such as methyl, ethyl, propyl, isopropyl, t-butyl, hexyl, phenyl, substituted phenyl, benzyl, or functional groups such as CH 2 F, CHF 2 , CF 3 , Si(CH 3 ) 3 , Si(CH 3 ) 2 (C 2 H 5 ), Si(CH 3 )(C 2 H 5 ) 2 , Si(C 2 H 5 ) 3 . Yet another mass-modification can be obtained by attaching homo- or heteropeptides through the nucleic acid molecule (e.g., detector (D)) or nucleoside triphosphates). One example, useful in generating mass-modified species with a mass increment of 57, is the attachment of oligoglycines (m) to nucleic acid molecules (r), e.g., mass-modifications of 74 (r=1, m=0), 131 (r=1, m=1), 188 (r=1, m=2), 245 (r=1, m=3) are achieved. Simple oligoamides also can be used, e.g., mass-modifications of 74 (r=1, m=0), 88 (r=2, m=0), 102 (r=3, m=0), 116(r=4, m=0), etc. are obtainable. Variations in additions to those set forth herein will be apparent to the skilled artisan.  
     [0135] Different mass-modified detector oligonucleotides can be used to simultaneously detect all possible variants/mutants simultaneously. Alternatively, all four base permutations at the site of a mutation can be detected by designing and positioning a detector oligonucleotide, so that it serves as a primer for a DNA/RNA polymerase with varying combinations of elongating and terminating nucleoside triphosphates. For example, mass modifications also can be incorporated during the amplification process.  
     [0136] A different multiplex detection format is one in which differentiation is accomplished by employing different specific capture sequences which are position-specifically immobilized on a flat surface (e.g., a ‘chip array’). If different target sequences T1-Tn are present, their target capture sites TCS1-TCSn will specifically interact with complementary immobilized capture sequences C1-Cn. Detection is achieved by employing appropriately mass differentiated detector oligonucleotides D1 -Dn, which are mass modifying functionalities M1-Mn.  
     [0137] o. Other Methods p Additional methods of analyzing nucleic acids include amplification-based methods including polymerase chain reaction (PCR), ligase chain reaction (LCR), mini-PCR, rolling circle amplification, autocatalytic methods, such as those using OJ replicase, TAS, 3SR, and any other suitable method known to those of skill in the art.  
     [0138] Other methods for analysis and identification and detection of polymorphisms, include but are not limited to, allele specific probes, Southern analyses, and other such analyses.  
     [0139] 2. Primers and Probes  
     [0140] Primers refer to nucleic acids which are capable of specifically hybridizing to a nucleic acid sequence which is adjacent to a polymorphic region of interest or to a polymorphic region and are extended. A primer can be used alone in a detection method, or a primer can be used together with at least one other primer or probe in a detection method. Primers can also be used to amplify at least a portion of a nucleic acid. For amplifying at least a portion of a nucleic acid, a forward primer (i.e., 5′ primer) and a reverse primer (i.e., 3′ primer) will preferably be used. Forward and reverse primers hybridize to complementary stands of a double stranded nucleic acid, such that upon extension from each primer, a double stranded nucleic acid is amplified.  
     [0141] Probes refer to nucleic acids which hybridize to the region of interest and which are not further extended. For example, a probe is a nucleic acid which hybridizes adjacent to or at a polymorphic region of a COX6B gene, a GPI-1 gene or another gene associated with cardiovascular disease and which by hybridization or absence of hybridization to the DNA of a subject will be indicative of the identity of the allelic variant of the polymorphic region of the gene. Preferred probes have a number of nucleotides sufficient to allow specific hybridization to the target nucleotide sequence. Where the target nucleotide sequence is present in a large fragment of DNA, such as a genomic DNA fragment of several tens or hundreds of kilobases, the size of a probe may have to be longer to provide sufficiently specific hybridization, as compared to a probe which is used to detect a target sequence which is present in a shorter fragment of DNA. For example, in some diagnostic methods, a portion of a COX6B gene, a GPI-1 gene or another gene associated with cardiovascular disease may first be amplified and thus isolated from the rest of the chromosomal DNA and then hybridized to a probe. In such a situation, a shorter probe will likely provide sufficient specificity of hybridization. For example, a probe having a nucleotide sequence of about 10 nucleotides may be sufficient.  
     [0142] Preferred primers and probes hybridize adjacent to or at the polymorphic sites described in TABLES 1-3. In addition, preferred primers include SEQ ID NOS.: 5, 10, 43, 48, 53, 58, 63, 68, 73, 78, 83, 88, 93, 98, 103, 108, 113, and 118.  
     [0143] Primers and probes (RNA, DNA (single-stranded or double-stranded), PNA and their analogs) described herein may be labeled with any detectable reporter or signal moiety including, but not limited to radioisotopes, enzymes, antigens, antibodies, spectrophotometric reagents, chemiluminescent reagents, fluorescent and any other light producing chemicals. Additionally, these probes may be modified without changing the substance of their purpose by terminal addition of nucleotides designed to incorporate restriction sites or other useful sequences, proteins, signal generating ligands such as acridinium esters, and/or paramagnetic particles.  
     [0144] These probes may also be modified by the addition of a capture moiety (including, but not limited to para-magnetic particles, biotin, fluorescein, dioxigenin, antigens, antibodies) or attached to the walls of microtiter trays to assist in the solid phase capture and purification of these probes and any DNA or RNA hybridized to these probes. Fluorescein may be used as a signal moiety as well as a capture moiety, the latter by interacting with an anti-fluorescein antibody.  
     [0145] Any probe or primer can be prepared according to methods well known in the art and described, e.g., in Sambrook, J. Fritsch, E. F., and Maniatis, T. (1989( Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. For example, discrete fragments of the DNA can be prepared and cloned using restriction enzymes. Alternatively, probes and primers can be prepared using the Polymerase Chain Reaction (PCR) using primers having an appropriate sequence.  
     [0146] Oligonucleotides may be synthesized by standard methods known in the art, e.g. by use of an automated DNA synthesizer (such as are commercially available from Biosearch (Novato, Calif.); Applied Biosystems (Foster City, Calif.), etc.). As examples, phosphorothioate oligonucleotides may be synthesized by the method of Stein et al. (1988, Nucl. Acids Res. 16:3209), methylphosphonate oligonucleotides can be prepared by use of controlled pore glass polymer supports (Sarin et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:7448-7451), etc.  
     [0147] H. Transgenic Animals  
     [0148] Methods for making transgenic animals using a variety of transgenes have been described in Wagner et al. (1981) Proc. Nat. Acad. Sc. U.S.A. 78: 5016; Stewart et al. (1982) Science 217: 1046; Constantini et al. (1981) Nature 294: 92; Lacy et al. (1983) Cell 34: 343; McKnight et al. (1983) Cell 34: 335; Brinstar et al. (1983) Nature 306: 332; Palmiter et al. (1982) Nature 300: 611; Palmiter et al. (1982) Cell 29: 701; and Palmiter et al. (1983) Science 222: 809. Such methods are described in U.S. Pat. Nos. 6,175,057; 6,180,849 and 6,133,502.  
     [0149] The term “transgene” is used herein to describe genetic material that has been or is about to be artificially inserted into the genome of a mammalian cell, particularly a mammalian cell of a living animal. The transgene is used to transform a cell, meaning that a permanent or transient genetic change, preferably a permanent genetic change, is induced in a cell following incorporation of exogenous DNA. A permanent genetic change is generally achieved by introduction of the DNA into the genome of the cell. Vectors for stable integration include, but are not limited to, plasmids, retroviruses and other animal viruses and YACS. Of interest are transgenic mammals, including, but are not limited to, cows, pigs, goats, horses and others, and particularly rodents, including rats and mice. Preferably, the transgenic-animals are mice.  
     [0150] Transgenic animals contain an exogenous nucleic acid sequence present as an extrachromosomal element or stably integrated in all or a portion of its cells, especially germ cells. Unless otherwise indicated, it will be assumed that a transgenic animal comprises stable changes to the germline sequence. During the initial construction of the animal, “chimeras” or “chimeric animals” are generated, in which only a subset of cells have the altered genome. Chimeras are primarily used for breeding purposes in order to generate the desired transgenic animal. Animals having a heterozygous alteration are generated by breeding of chimeras. Male and female heterozygotes are typically bred to generate homozygous animals.  
     [0151] The exogenous gene is usually either from a different species than the animal host, or is otherwise altered in its coding or non-coding sequence. The introduced gene may be a wild-type gene, naturally occurring polymorphism (e.g., as described for COX6B, GPI-1 and other genes associated with cardiovascular disease) or a genetically manipulated sequence, for example having deletions, substitutions or insertions in the coding or non-coding regions. When the introduced gene is a coding sequence, it is usually operably linked to a promoter, which may be constitutive or inducible, and other regulatory sequences required for expression in the host animal.  
     [0152] Transgenic animals can comprise other genetic alterations in addition to the presence of alleles of COX6B and/or GPI-1 genes. For example, the genome can be altered to affect the function of the endogenous genes, contain marker genes, or contain other genetic alterations (e.g., alleles of other genes associated with cardiovascular disease).  
     [0153] A “knock-out” of a gene means an alteration in the sequence of the gene that results in a decrease of function of the target gene, preferably such that target gene expression is undetectable or insignificant. A knock-out of an endogenous COX6B or GPI-1 gene means that function of the gene has been substantially decreased so that expression is not detectable or only present at insignificant levels. “Knock-out” transgenics can be transgenic animals having a heterozygous knock-out of the COX6B or GPI-1 gene or a homozygous knock-out of one or both of these genes. “Knock-outs” also include conditional knock-outs, where alteration of the target gene can occur upon, for example, exposure of the animal to a substance that promotes target gene alteration, introduction of an enzyme hat promotes recombination at the target gene site (e.g., Cre in the Cre-lox system), or other method for directing the target gene alteration postnatally.  
     [0154] A “knock-in” of a target gene means an alteration in a host cell genome that results in altered expression (e.g., increased (including ectopic)) of the target gene, e.g., by introduction of an additional copy of the target gene, or by operatively inserting a regulatory sequence that provides for enhanced expression of an endogenous copy of the target gene. “Knock-in” transgenics of interest can be transgenic animals having a knock-in of the COX6B or GPI-1. Such transgenics can be heterozygous or homozygous for the knock-in gene. “Knock-ins” also encompass conditional knock-ins.  
     [0155] A construct is suitable for use in the generation of transgenic animals if it allows the desired level of expression of a COX6B or GPI-1 encoding sequence or the encoding sequence of another gene associated with cardiovascular disease. Methods of isolating and cloning a desired sequence, as well as suitable constructs for expression of a selected sequence in a host animal, are well known in the art and are described below.  
     [0156] For the introduction of a gene into the subject animal, it is generally advantageous to use the gene as a gene construct wherein the gene is ligated downstream of a promoter capable of and operably linked to expressing the gene in the subject animal cells. Specifically, a transgenic non-human mammal showing high expression of the desired gene can be created by microinjecting a vector ligated with said gene into a fertilized egg of the subject non-human mammal (e.g., rat fertilized egg) downstream of various promoters capable of expressing the protein and/or the corresponding protein derived from various mammals (rabbits, dogs, cats, guinea pigs, hamsters, rats, mice etc., preferably rats etc.) Useful vectors include  Escherichia coli -derived plasmids,  Bacillus subtilis -derived plasmids, yeast-derived plasmids, bacteriophages such as lambda, phage, retroviruses such as Moloney leukemia virus, and animal viruses such as vaccinia virus or baculovirus.  
     [0157] Useful promoters for such gene expression regulation include, for example, promoters for genes derived from viruses (cytomegalovirus, Moloney leukemia virus, JC virus, breast cancer virus etc.), and promoters for genes derived from various mammals (humans, rabbits, dogs, cats, guinea pigs, hamsters, rats, mice etc.) and birds (chickens etc.) (e.g., genes for albumin, insulin II, erythropoietin, endothelin, osteocalcin, muscular creatine kinase, platelet-derived growth factor beta, keratins K1, K10 and K14, collagen types I and II, atrial natriuretic factor, dopamine beta-hydroxylase, endothelial receptor tyrosine kinase (generally abbreviated Tie2), sodium-potassium adenosine triphosphorylase (generally abbreviated Na,K-ATPase), neurofilament light chain, metallothioneins I and IIA, metalloproteinase I tissue inhibitor, MHC class I antigen (generally abbreviated H-2L), smooth muscle alpha actin, polypeptide chain elongation factor 1 alpha (EF-1 alpha), beta actin, alpha and beta myosin heavy chains, myosin light chains 1 and 2, myelin base protein, serum amyloid component, myoglobin, renin etc.).  
     [0158] It is preferable that the above-mentioned vectors have a sequence for terminating the transcription of the desired messenger RNA in the transgenic animal (generally referred to as terminator); for example, gene expression can be manipulated using a sequence with such function contained in various genes derived from viruses, mammals and birds. Preferably, the simian virus SV40 terminator etc. are commonly used. Additionally, for the purpose of increasing the expression of the desired gene, the splicing signal and enhancer region of each gene, a portion of the intron of a eukaryotic organism gene may be ligated 5′ upstream of the promoter region, or between the promoter region and the translational region, or 3′ downstream of the translational region as desired.  
     [0159] A translational region for a protein of interest can be obtained using the entire or portion of genomic DNA of blood, kidney or fibroblast origin from various mammals (humans, rabbits, dogs, cats, guinea pigs, hamsters, rats, mice etc.) or of various commercially available genomic DNA libraries, as a starting material, or using complementary DNA prepared by a known method from RNA of blood, kidney or fibroblast origin as a starting material. Also, an exogenous gene can be obtained using complementary DNA prepared by a known method from RNA of human fibroblast origin as a starting material. All these translational regions can be utilized in transgenic animals.  
     [0160] To obtain the translational region, it is possible to prepare DNA incorporating an exogenous gene encoding the protein of interest in which the gene is ligated downstream of the above-mentioned promoter (preferably upstream of the translation termination site) as a gene construct capable of being expressed in the transgenic animal.  
     [0161] DNA constructs for random integration need not include regions of homology to mediate recombination. Where homologous recombination is desired, the DNA constructs will comprise at least a portion of the target gene with the desired genetic modification, and will include regions of homology to the target locus. Conveniently, markers for positive and negative selection are included. Methods for generating cells having targeted gene modifications through homologous recombination are known in the art. For various techniques for transfecting mammalian cells, see Keown et al. (1990) Methods in Enzymology 185:527-537.  
     [0162] The transgenic animal can be created by introducing a COX6B or GPI-1 gene construct into, for example, an unfertilized egg, a fertilized egg, a spermatozoon or a germinal cell containing a primordial germinal cell thereof, preferably in the embryogenic stage in the development of a non-human mammal (more preferably in the single-cell or fertilized cell stage and generally before the 8-cell phase), by standard means, such as the calcium phosphate method, the electric pulse method, the lipofection method, the agglutination method, the microinjection method, the particle gun method, the DEAE-dextran method and other such method. Also, it is possible to introduce a desired COX6B or GPI-1 gene into a somatic cell, a living organ, a tissue cell, or the like, by gene transformation methods, and utilize it for cell culture, tissue culture etc. Furthermore, these cells may be fused with the above-described germinal cell by a commonly known cell fusion method to create a transgenic animal.  
     [0163] For embryonic stem (ES) cells, an ES cell line may be employed, or embryonic cells may be obtained freshly from a host, e.g. mouse, rat, guinea pig, etc. Such cells are grown on an appropriate fibroblast-feeder layer or grown in the presence of appropriate growth factors, such as leukemia inhibiting factor (LIF). When ES cells have been transformed, they may be used to produce transgenic animals. After transformation, the cells are plated onto a feeder layer in an appropriate medium. Cells containing the construct may be detected by employing a selective medium. After sufficient time for colonies to grow, they are picked and analyzed for the occurrence of homologous recombination or integration of the construct. Those colonies that are positive may then be used for embryo manipulation and blastocyst injection. Blastocysts are obtained from 4 to 6 week old superovulated females. The ES cells are trypsinized, and the modified cells are injected into the blastocoel of the blastocyst. After injection, the blastocysts are returned to each uterine horn of pseudopregnant females. Females are then allowed to go to term and the resulting litters screened for mutant cells having the construct. By providing for a different phenotype of the blastocyst and the ES cells, chimeric progeny can be readily detected. The chimeric animals are screened for the presence of the modified gene and males and females having the modification are mated to produce homozygous progeny. If the gene alterations cause lethality at some point in development, tissues or organs can be maintained as allogeneic or congenic grafts or transplants, or in in vitro culture.  
     [0164] Animals containing more than one transgene, such as allelic variants of COX6B and/or GPI-1 and/or other genes associated with cardiovascular disease can be made by sequentially introducing individual alleles into an animal in order to produce the desired phenotype (manifestation or predisposition to cardiovascular disease).  
     [0165] I. Effect of Allelic Variants on the Encoded Protein and Disease Related Phenotype  
     [0166] The effect of an allelic variant on a COX6B or GPI-1 protein (altered amount, stability, location and/or activity) can be determined according to methods known in the art. Alielic variants of the COX6B and GPI-1 genes can be assayed individually or in combination with other variants known to be associated with cardiovascular disease.  
     [0167] If the mutation is located in an intron, the effect of the mutation can be determined, e.g., by producing transgenic animals in which the allelic variant linked to lipid metabolism and/or cardiovascular disease has been introduced and in which the wild-type gene or predominant allele may have been knocked out. Comparison of the level of expression of the protein in the mice transgenic for the allelic variant with mice transgenic for the predominant allele will reveal whether the mutation results in increased or decreased synthesis of the associated protein and/or aberrant tissue distribution of the associated protein. Such analysis could also be performed in cultured cells, in which the human variant allele gene is introduced and, e.g., replaces the endogenous gene in the cell. Thus, depending on the effect of the alteration a specific treatment can be administered to a subject having such a mutation. Accordingly, if the mutation results in decreased production of a COX6B or GPI-1 protein, the subject can be treated by administration of a compound which increases synthesis, such as by increasing COX6B or GPI-1 gene expression, and wherein the compound acts at a regulatory element different from the one which is mutated. Alternatively, if the mutation results in increased COX6B or GPI-1 protein levels, the subject can be treated by administration of a compound which reduces protein production, e.g., by reducing COX6B or GPI-1 gene expression or a compound which inhibits or reduces the activity of COX6B or GPI-1 protein.  
     [0168] J. Diagnostic and Prognostic Assays  
     [0169] Typically, an individual allelic variant that associates with a risk factor for cardiovascular disease will not be used in isolation as a prognosticator for a subject developing high cholesterol, low HDL or cardiovascular disease. An allelic variant typically will be one of a plurality of indicators that are utilized. The other indicators may be the manifestation of other risk factors for cardiovascular disease, e.g., family history, high blood pressure, weight, activity level, etc., or additional allelic variants in the same or other genes associated with altered lipid metabolism and/or cardiovascular disease.  
     [0170] Useful combinations of allelic variants of the COX6B gene and/or the GPI-1 gene can be determined by examining combinations of variants of these genes, which are assayed individually or assayed simultaneously using multiplexing methods as described above or any other labelling method that allows different variants to be identified. In particular, variants of COX6B gene and/or the GPI-1 gene may be assayed using kits (see below) or any of a variety microarrays known to those in the art. For example, oligonucleotide probes comprising the polymorphic regions surrounding any polymorphism in the COX6B or GPI-1 gene may be designed and fabricated using methods such as those described in U.S. Pat. Nos. 5,492,806; 5,525,464; 5,695,940; 6,018,041; 6,025,136; WO 98/30883; WO 98/56954; WO99/09218; WO 00/58516; WO 00/58519, or references cited therein. Similarly one of skill in the art can determine useful combinations of allelic variants of the COX6B and/or GPI-1 genes along with variants of other genes associated with cardiovascular disease.  
     [0171] K. Pharmacogenomics  
     [0172] It is likely that subjects having one or more different allelic variants of the COX6B or GPI-1 polymorphic regions will respond differently to therapeutic drugs to treat cardiovascular disease or conditions. For example, there are numerous drugs available for lowering cholesterol levels: including lovastatin (MEVACOR; Merck &amp; Co.), simvastatin (XOCOR; Merck &amp; Co.), dextrothyroxine (CHOLOXIN; Knoll Pharmaceutical Co.), pamaqueside (Pfizer), cholestryramine (QUESTRAN; Bristol-Myers Squibb), colestipol (COLESTID; Pharmacia &amp; Upjohn), acipomox (Pharmacia &amp; Upjohn), fenofibrate (LIPIDIL), gemfibrozil (LOPID; Warner-Lambert), cerivastatin (LIPOBAY; Bayer), fluvastatin (LESCOL; Novartis), atorvastatin (LIPITOR, Warner-Lambert), etofylline clofibrate (DUOLIP; Merckle (Germany)), probucol (LORELCO; Hoechst Marion Roussel), omacor (Pronova (Norway), etofibrate (Merz (Germany), clofibrate (ATROMID-S; Wyeth-Ayerst (AHP)), and niacin (numerous manufacturers). All patients do not respond identically to these drugs. Alleles of the COX6B or the GPI-1 gene which associate with altered lipid metabolism will be useful alone or in conjunction with markers in other genes associated with the development of cardiovascular disease to predict a subject&#39;s response to a therapeutic drug. For example, multiplex primer extension assays or microarrays comprising probes for alleles are useful formats for determining drug response. A correlation between drug responses and specific alleles or combinations of alleles of the COX6B or GPI-1 genes and other genes associated with cardiovascular disease can be shown, for example, by clinical studies wherein the response to specific drugs of subjects having different allelic variants of polymorphic regions of the COX6B or GPI-1 genes alone or in combination with allelic variants of other genes are compared. Such studies can also be performed using animal models, such as mice having various alleles and in which, e.g., the endogenous COX6B or GPI-1 genes have been inactivated such as by a knock-out mutation. Test drugs are then administered to the mice having different alleles and the response of the different mice to a specific compound is compared. Accordingly, assays, microarrays and kits are provided for determining the drug which will be best suited for treating a specific disease or condition in a subject based on the individual&#39;s genotype. For example, it will be possible to select drugs which will be devoid of toxicity, or have the lowest level of toxicity possible for treating a subject having a disease or condition, e.g., cardiovascular disease or high cholesterol or low HDL.  
     [0173] L. Kits  
     [0174] Kits can be used to indicate whether a subject is at risk of developing high cholesterol, low HDL and/or cardiovascular disease. The kits can also be used to determine if a subject who has high cholesterol or low HDL carries associated variants in the COX6B or GPI-1 genes or other cardiovascular disease-related genes. This information could be used, e.g., to optimize treatment of such individuals as a particular genotype may be associated with drug response.  
     [0175] In preferred embodiments, the kits comprise a probe or primer which is capable of hybridizing adjacent to or at a polymorphic region of a OX6B or GPI-1 gene and thereby identifying whether the COX6B or GPI-1 gene contains an allelic variant which is associated with cardiovascular disease. Primers or probes that specifically hybridize at or adjacent to the SNPs described in Tables 1-3 could be included. In particular, primers or probes which comprise the sequences of SEQ ID NOs.: 5, 10, 43, 48, 53, 58, 63, 68, 73, 78, 83, 88, 93, 98, 103, 108, 113, and 118 could be included in the kits. The kits preferably further comprise instructions for use in carrying out assays, interpreting results and diagnosing a subject as having a predisposition toward developing high cholesterol, low HDL and/or cardiovascular disease.  
     [0176] Preferred kits for amplifying a region of a COX6B gene, GPI-1 gene, or other genes associated with cardiovascular disease (such as those listed in Table 3) comprise two primers which flank a polymorphic region of the gene of interest. For example primers can comprise the sequences of SEQ ID NOs.: 3, 4, 8, 9, 41, 42, 46, 47, 51, 52, 56, 57, 61, 62, 66, 67, 71, 72, 76, 77, 81, 82, 86, 87, 91, 92, 96, 97, 101, 102, 106, 107, 111, 112, 116, and 117. For other assays, primers or probes hybridize to a polymorphic region or 5′ or 3′ to a polymorphic region depending on which strand of the target nucleic acid is used. For example, specific probes and primers comprise sequences designated as SEQ ID NOs: 5, 10, 43, 48, 53, 58, 63, 68, 73, 78, 83, 88, 93, 98, 103, 108, 113, and 118. Those of skill in the art can synthesize primers and probes which hybridize adjacent to or at the polymorphic regions described in TABLES 1-3 and other SNPs in genes associated with cardiovascular disease.  
     [0177] Yet other kits comprise at least one reagent necessary to perform an assay. For example, the kit can comprise an enzyme, such as a nucleic acid polymerase. Alternatively the kit can comprise a buffer or any other necessary reagent.  
     [0178] Yet other kits comprise microarrays of probes to detect allelic variants of COX6B, GPI-1, and other genes associated with cardiovascular disease. The kits further comprise instructions for their use and interpreting the results.  
     [0179] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention. The practice of methods and development of the products provided herein employ, unless otherwise indicated, conventional techniques of cell biology, cell culture, molecular biology, transgenic biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See, for example, Molecular Cloning A Laboratory Manual, 2nd Ed., ed. by Sambrook, Fritsch and Maniatis (Cold Spring Harbor Laboratory Press: 1989); DNA Cloning, Volumes I and II (D. N. Glover ed., 1985); Oligonucleotide Synthesis (M. J. Gait ed., 1984); Mullis et al. U.S. Pat. No. 4,683,195; Nucleic Acid Hybridization (B. D. Hames &amp; S. J. Higgins eds. 1984); Transcription and Translation (B. D. Hames &amp; S. J. Higgins eds. 1984); Culture of Animal Cells (R. I. Freshney, Alan R. Liss, Inc., 1987); Immobilized Cells and Enzymes (IRL Press, 1986); B. Perbal, A Practical Guide To Molecular Cloning (1984); the treatise, Methods In Enzymology (Academic Press, Inc., New York); Gene Transfer Vectors For Mammalian Cells (J. H. Miller and M. P. Calos eds., 1987, Cold Spring Harbor Laboratory); Methods In Enzymology, Vols. 154 and 155 (Wu et al. eds., Immunochemical Methods In Cell and Molecular Biology (Mayer and Walker, eds., Academic Press, London, 1987); Handbook of Experimental Immunology, Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986); Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986).  
     EXAMPLE 1  
     [0180] Isolation of DNA from Blood Samples of a Stratified Population  
     [0181] Blood samples were obtained from a population of unrelated Caucasian women between the ages of 18-79 (average age=48). The women had, no response to media campaigns, attended the Twin Research Unit at the St. Thomas Hospital in London, England. For current purposes, only one member of a twin pair was used to insure that all observations were independent. Blood samples from 1400 unrelated individuals were measured for levels of cholesterol and HDL. Cholesterol and HDL level in blood samples were quantitated using standard assay methods.  
     [0182] The population was stratified into pools of 200 people, which represented the lower extreme and the upper extreme for serum levels of cholesterol and HDL.  
                                  Cholesterol                             Pool 1:   Individuals were considered to have low               cholesterol (0.12-3.6 mmoles/L).           Pool 2:   Individuals were considered to have high               cholesterol (5.25-11.57 mmoles/L).                 HDL                             Pool 3:   Individuals were considered to have low levels               of HDL (0.240-1.11 mmoles/L)           Pool 4:   Individuals were considered to have high levels               of HDL (2.10-3.76 mmoles/L).                      
 
     [0183] DNA Extraction Protocol  
     [0184] DNA was extracted from blood samples of each of the pools by utilizing the following protocol.  
     [0185] Section 1  
     [0186] 1. Blood was extracted into EDTA tubes.  
     [0187] 2. Blood sample was spun at 3,000 rpm for 10 minutes in a clinical centrifuge.  
     [0188] 3. The buffy coat (the leukocytes, a yellowish layer of cells on top of the red blood cells) was removed and pooled into a 1 ml conical tube.  
     [0189] 4. 0.9% saline was added to fill the tube and resuspend the leucocytes. Sample were immediately further processed or stored at 4° C. for 24 hrs.  
     [0190] 5. The sample was spun at 2,500 rpm for 10 minutes.  
     [0191] 6. The buffy coat was again removed as cleanly as possible leaving behind any red cells, the sample was suspended in red cell lysis buffer and left for 20 minutes at 4° C.  
     [0192] 7. The sample was spun again at 2,500 rpm for 10 minutes. If a pellet of unlysed red cells remained lying above the leucocytes the treatment with red cell lysis buffer was repeated.  
     [0193] 8. The leucocyte pellet was resuspended in 2 ml 0.9% saline.  
     [0194] 9. The DNA was liberated by the addition of leucocyte lysis buffer—the tube was capped and gently inverted several times, until the liquid became viscous with DNA. The samples were handled with care to avoid shearing and damage to the DNA.  
     [0195] 10. Samples were frozen for storage prior to full extraction.  
     [0196] Section 2  
     [0197] 11. 2 ml of 5 M sodium perchlorate was added to the thawed sample and mixed by inversion. The sample was heated to 60° C. for 30-40 minutes to fully denature proteins.  
     [0198] 12. An equal volume of chloroform/isoamyl alcohol (24:1) was added at room temperature and the sample mixed for 10 minutes.  
     [0199] 13. The sample was spun without a break at 3,000 rpm for 10 minutes.  
     [0200] 14. The top aqueous phase was removed into a clean tube and two volumes of cold 100% ethanol added and mixed by inversion to precipitate DNA.  
     [0201] 15. The DNA was removed using a sterile loop and resuspended in 1-5 ml TE buffer depending on the DNA yield.  
     [0202] 16. The optical density was measured at 260 and 280 nm to check yield and purity of the DNA sample. For use in Examples 2 and 3, all DNA had an absorbance ratio of 1.6 at 260/280, a total yield of 32 μg and a concentration of 10 ng/μl. If initial purity levels were unacceptable a re-extraction was carried out (sections 12-15 above).  
     EXAMPLE 2  
     [0203] Detection of an Association Between an SNP at Position 86 of the Human COX6B Gene and High Cholesterol  
     [0204] DNA samples (as prepared in Example 1), representing 200 women, from the lower extreme, pool 1 (low levels of cholesterol) and the upper extreme, pool 2 (high levels of cholesterol) were amplified and analyzed for genetic differences using a MassEXTEND™ assay detection method. For each pool, single nucleotide polymorphisms were examined throughout the entire genome to detect differences in allelic frequency of a variant allele between the pools.  
     [0205] PCR Amplification of Samples from Pools 1 and 2  
     [0206] PCR primers were synthesized by Operon (Alameda, Calif.) using phosphoramidite chemistry. Amplification of the COX6B target sequence was carried out in two 50 μl PCR reactions with 100 ng of pooled human genomic DNA, obtained as described in Example 1, taken from samples in pool 1 or pool 2, although amounts ranging from 100 ng to 1 ug could be used. Individual DNA concentrations within the pooled samples were present in equal concentration with a final concentration of 0.5 ng. Each reaction contained 1×PCR buffer (Qiagen, Valencia, Calif.), 200 μM dNTPs, 1U Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl 2 , and 25 pmols of the long primer containing both the universal primer sequence and the target specific sequence 5′-AGCGGATAACAATTTCACACAGGTAGTCTGGTTCTGGTTGGGG-3′ (SEQ ID NO.: 4), 2 pmoles of the short primer 5′-AGGATTCAGCACCATGGC-3′ (SEQ ID NO.: 3) and 10 pmoles of a biotinylated universal primer complementary to the 5′ end of the PCR amplicon 5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ ID NO.: 121). Alternatively, the biotinylated universal primer could be 5′-GGCGCACGCCTCCACG-3′ (SEQ ID NO.: 122). After an initial round of amplification with the target with the specific forward (long) and reverse primer (short), the 5′ biotinylated universal primer then hybridized and acted as a reverse primer thereby introducing a 3′ biotin capture moiety into the molecule. The amplification protocol results in a 5′-biotinylated double stranded DNA amplicon and dramatically reduces the cost of high throughput genotyping by eliminating the need to 5′ biotin label each forward primer used in a genotyping. Thermal cycling was performed in 0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler (Waltham, Mass.) (calculated temperature) with the following cycling parameters: 94° C. for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for 30 sec, 72° C. for 60 sec; 72° C. 3 min.  
     [0207] Immobilization of DNA  
     [0208] The 50 μl PCR reaction was added to 25 μl of streptavidin coated magnetic bead (Dynal, Lake Success, N.Y.) prewashed three times and resuspended in 1 M NH 4 Cl, 0.06 M NH 4 OH. The PCR amplicons were allowed to bind to the beads for 15 minutes at room temperature. The beads were then collected with a magnet and the supernatant containing unbound DNA was removed. The unbound strand was released from the double stranded amplicons by incubation in 100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.  
     [0209] Genotyping  
     [0210] The frequency of the alleles at position 86 in the COX6B gene was measured using the MassEXTEND™ assay and MALDI-TOF. The SNP identified at position 86 of COX6B in the GenBank sequence is represented as a C to T transversion. The MassEXTEND™ assay used detected the sequence of the complementary strand, thus the SNP was represented as G to A in the primer extension products. The DNA coated magnetic beads were resuspended in 26 mM Tris-HCL pH 9.5, 6.5 mM MgCl 2  and 50 mM each of dTTPs and 50 mM each of ddCTP, ddATP, ddGTP, 2.5 U of a thermostable DNA polymerase (Amersham Pharmacia Biotech, Piscataway, N.J.) and 20 pmoles of a template specific oligonucleotide primer 5′-AATCAAGAACTACAAGAC-3′ (SEQ ID NO.: 5) (Operon, Alameda, Calif.). Primer extension occurred with three cycles of oligonucleotide primer hybridization and extension. The extension products were analyzed after denaturation from the template with 50 mM NH 4 Cl and transfer of 150 nl of each sample to a silicon chip preloaded with 150 nl of H3PA (3-hydroxy picolinic acid) (Sigma Aldrich, St Louis, Mo.) matrix material. The sample material was allowed to crystallize and analyzed by MALDI-TOF (Bruker Daltonics, Billerica, Mass.; PerSeptive, Foster City, Calif.). The mass of the primer used in the MassEXTEND™ reaction was 5493.70 daltons. The predominant allele is extended by the addition of ddC, which has a mass of 5766.90 daltons. The allelic variant results in the addition of dT and ddG to the primer to produce an extension product having a mass of 6111.10 daltons.  
     [0211] In addition to being analyzed as part of a pool, each individual sample (0.5 ng) was amplified as described above and analyzed individually using a MassEXTEND™ reaction as described above.  
     [0212] Pooled populations of women (200 women per pool) with high cholesterol (pool 2) showed an increase in the frequency of the A allele at nucleotide position 86 of COX6B as compared with those with low levels of cholesterol (pool 1) (see FIG. 1). The association of this allelic variant of the COX6B gene with high cholesterol gave a statistically significant value of 14.30 using a 1-degree-of-freedom chi-squared test of association. In other words, the increase of 2.75% to 9.05% is significant, with a p value of 0.000156 (see FIG. 1). The genotype of each of the individuals in the pooled population was also determined by carrying out MassEXTEND™ reactions on each DNA samples individually. These analysis confirmed the pooling data showing that there was an increase in the frequency of the A allele of 2.27% to 9.93%, (p=0.0000061). The genotypes in pool 2 showed a decrease in the homozygous GG genotype from 95.4% to 82.35% and an increase in the heterozygous GA genotype from 4.55% to 15.44%. None of the individuals with low levels of serum cholesterol exhibited the homozygous AA genotype.  
     EXAMPLE 3  
     [0213] Detection of an Association Between an SNP at Position 2577 of the Human GPI-1 Gene and Low HDL  
     [0214] DNA samples (as prepared in Example 1), representing 200 women, from pool 3 (low level of HDL) and pool 4 (high levels of HDL) were amplified and analyzed for genetic differences using a MassEXTEND™ detection method. For each pool, SNPs were examined throughout the genome to detect differences in allelic frequency of variant alleles between the pools.  
     [0215] PCR Amplification of Samples from Pools 3 and 4  
     [0216] PCR primers were synthesized by Operon (Alameda, Calif.) using phosphoramidite chemistry. Amplification of the GPI-1 target sequence was carried out in single 50 μl PCR reaction with 100 ng of pooled human genomic DNA (200 samples), obtained as described in Example 1, taken from samples in pool 3 or pool 4, although amounts ranging from 100 ng to 1 ug could be used. Individual DNA concentrations within the pooled samples were present in equal concentration with the final concentration of 0.5 ng. Each reaction contained 1×PCR buffer (Qiagen, Valencia, Calif.), 200 uM dNTPs, 1U Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl 2 , and 25 pmols of the forward primer containing both the universal primer sequence and the target specific short sequence 5′-AGCAGGGCTTCCTCCTTC-3′ (SEQ ID NO.: 8) 2 pmoles of the long primer 5′-AGCGGATAACAATTTCACACAGGTGACCCAGCCGTACCTATTC-3′ (SEQ ID NO.: 9) and 10 pmoles of a biotinylated universal primer complementary to the 5′ end of the PCR amplicon 5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ ID NO.: 121). After an initial round of amplification with the target with the specific forward (long) and reverse primer (short), the 5′ biotinylated universal primer then hybridized and acted as a reverse primer thereby introducing a 3′ biotin capture moiety into the molecule. The amplification protocol results in a 5′-biotinylated double stranded DNA amplicon and dramatically reduces the cost of high throughput genotyping by eliminating the need to 5′ biotin label each forward primer used in a genotyping. Thermal cycling was performed in 0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler (Watham, Mass.) (calculated temperature) with the following cycling parameters: 94° C. for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for 30 sec, 72° C. for 60 sec; 72° C. 3 min.  
     [0217] Immobilization of DNA  
     [0218] The 50 μl PCR reaction was added to 25 μl of streptavidin coated magnetic bead (Dynal, Lake Success, N.Y.) prewashed three times and resuspended in 1 M NH 4 Cl, 0.06 M NH 4 OH. The PCR amplicons were allowed to bind to the beads for 15 minutes at room temperature. The beads were then collected with a magnet and the supernatant containing unbound DNA was removed. The unbound strand was released from the double stranded amplicons by incubation in 100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.  
     [0219] Genotyping  
     [0220] The frequency of the alleles at position 2577 in the GPI-1 gene was measured using the MassEXTEND™ assay and MALDI-TOF. The SNP identified at position 2577 of GPI-1 in the GenBank sequence is represented as a G to A transversion. The MassEXTEND™ assay used detected this sequence, thus the SNP was represented as C to T in the primer extension products. The DNA coated magnetic beads were resuspended in 26 mM Tris-HCL pH 9.5, 6.5 mM MgCl 2  and 50 mM each of dTTPs and 50 mM each of ddCTP, ddATP, ddGTP, 2.5 U of a thermostable DNA polymerase (Amersham Pharmacia Biotech, Piscataway, N.J.) and 20 pmoles of a template specific oligonucleotide primer 5′-AAGGGAGACAGATTTGGC-3′ (SEQ ID NO.: 10) (Operon, Alameda, Calif.). Primer extension occurred with three cycles of oligonucleotide primer hybridization and extension. The extension products were analyzed after denaturation from the template with 50 mM NH 4 Cl and transfer of 150 nl each sample to a silicon chip preloaded with 150 nl of H3PA matrix material. The sample material was allowed to crystallize and analyzed by MALDI-TOF (Bruker Daltonics, Billerica, Mass.; PerSeptive, Foster City, Calif.). The mass of the primer used in the MassEXTEND™ reaction was 561 2.70 daltons. The predominant allele is extended by the addition of ddC, which has a mass of 5885.90 daltons. The allelic variant results in the addition of dT and ddG to the primer to produce an extension product having a mass of 6230.10 daltons.  
     [0221] In addition to being analyzed as a pool, each individual sample (0.5 ng) was amplified as described above and analyzed individually using the MassEXTEND™ reaction as described above.  
     [0222] Pooled populations of women (200 women per pool) with low HDL (pool 3) showed an increase in the T allele of 11.33% at nucleotide position 2577 as compared with those with high levels of HDL (pool 4). The association of this allelic variant of the GPI-1 gene with low HDL gave a statistically significant value of 15.04 using a 1-degree-of-freedom chi-squared test of association. In other words, the increase of 16.23% to 27.57% is significant, with a p value of 0.0001064 (see FIG. 2). The genotype of each of the individuals in the pooled population was also determined by carrying out individual MassEXTEND™ reactions on individual DNA samples. These analysis confirmed the pooling data showing that there was an increase in the frequency of the T allele of 19.49% to 26.1%, (p=0.024). The measured genotypes in pool 3 showed a decrease in the homozygous CC genotype from 65.24% to 54.21% and an increase in the heterozygous CT genotype from 30.51% to 39.25%. The homozygous TT genotypes increased 2.3%.  
     [0223] Since modifications will be apparent to those of skill in this art, it is intended that this invention be limited only by the scope of the appended claims.  
 
    
     
       
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                                                SEQUENCE LISTING  
               
               
                   
               
               
                   
               
               
                 &lt;160&gt; NUMBER OF SEQ ID NOS: 122  
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 1  
               
               
                 &lt;211&gt; LENGTH: 439  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo Sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (45)...(305)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 1  
               
               
                   
               
               
                 ttgagctgca ggttgaatcc ggggtgcctt taggattcag cacc atg gcg gaa gac      56  
               
               
                                                                  Met Ala Glu Asp  
               
               
                                                                   1  
               
               
                   
               
               
                 atg gag acc aaa atc aag aac tac aag acc gcc cct ttt gac agc cgc      104  
               
               
                 Met Glu Thr Lys Ile Lys Asn Tyr Lys Thr Ala Pro Phe Asp Ser Arg  
               
               
                  5                   10                  15                  20  
               
               
                   
               
               
                 ttc ccc aac cag aac cag act aga aac tgc tgg cag aac tac ctg gac      152  
               
               
                 Phe Pro Asn Gln Asn Gln Thr Arg Asn Cys Trp Gln Asn Tyr Leu Asp  
               
               
                                  25                  30                  35  
               
               
                   
               
               
                 ttc cac cgc tgt cag aag gca atg acc gct aaa gga ggc gat atc tct      200  
               
               
                 Phe His Arg Cys Gln Lys Ala Met Thr Ala Lys Gly Gly Asp Ile Ser  
               
               
                              40                  45                  50  
               
               
                   
               
               
                 gtg tgc gaa tgg tac cag cgt gtg tac cag tcc ctc tgc ccc aca tcc      248  
               
               
                 Val Cys Glu Trp Tyr Gln Arg Val Tyr Gln Ser Leu Cys Pro Thr Ser  
               
               
                          55                  60                  65  
               
               
                   
               
               
                 tgg gtc aca gac tgg gat gag caa cgg gct gaa ggc acg ttt ccc ggg      296  
               
               
                 Trp Val Thr Asp Trp Asp Glu Gln Arg Ala Glu Gly Thr Phe Pro Gly  
               
               
                      70                  75                  80  
               
               
                   
               
               
                 aag atc tga actggctgca tctccctttc ctctgtcctc catccttctc              345  
               
               
                 Lys Ile  *  
               
               
                  85  
               
               
                   
               
               
                 ccaggatggt gaagggggac ctggtaccca gtgatcccca ccccaggatc ctaaatcatg    405  
               
               
                   
               
               
                 acttacctgc taataaaaac tcattggaaa agtg                                439  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 2  
               
               
                 &lt;211&gt; LENGTH: 86  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo Sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 2  
               
               
                   
               
               
                 Met Ala Glu Asp Met Glu Thr Lys Ile Lys Asn Tyr Lys Thr Ala Pro  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Phe Asp Ser Arg Phe Pro Asn Gln Asn Gln Thr Arg Asn Cys Trp Gln  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Asn Tyr Leu Asp Phe His Arg Cys Gln Lys Ala Met Thr Ala Lys Gly  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Asp Ile Ser Val Cys Glu Trp Tyr Gln Arg Val Tyr Gln Ser Leu  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Cys Pro Thr Ser Trp Val Thr Asp Trp Asp Glu Gln Arg Ala Glu Gly  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Thr Phe Pro Gly Lys Ile  
               
               
                                 85  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 3  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: PCR Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 3  
               
               
                   
               
               
                 aggattcagc accatggc                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 4  
               
               
                 &lt;211&gt; LENGTH: 43  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: PCR Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 4  
               
               
                   
               
               
                 agcggataac aatttcacac aggtagtctg gttctggttg ggg                       43  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 5  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: MassExtend primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 5  
               
               
                   
               
               
                 aatcaagaac tacaagac                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 6  
               
               
                 &lt;211&gt; LENGTH: 2921  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo Sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (103)...(1848)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 6  
               
               
                   
               
               
                 cagcgagcgc cgtcgtctgc ccgggcccgc ccatcggggt ccccaacccc atccggaccc     60  
               
               
                   
               
               
                 cgccgcccga gcgcgcggcc ccggaagcac ccgcctcccg gc atg gtg ctc aag       114  
               
               
                                                                Met Val Leu Lys  
               
               
                                                                 1  
               
               
                   
               
               
                 gcc ttc ttc ccc acg tgc tgc gtc tcg gcg gac agc ggg ctg ctg gtg      162  
               
               
                 Ala Phe Phe Pro Thr Cys Cys Val Ser Ala Asp Ser Gly Leu Leu Val  
               
               
                  5                   10                  15                  20  
               
               
                   
               
               
                 gga cgg tgg gtg ccg gag cag agc agc gcc gtg gtc ctg gcg gtc ctg      210  
               
               
                 Gly Arg Trp Val Pro Glu Gln Ser Ser Ala Val Val Leu Ala Val Leu  
               
               
                                  25                  30                  35  
               
               
                   
               
               
                 cac ttt ccc ttc atc ccc atc cag gtc aag cag ctc ctg gcc cag gtg      258  
               
               
                 His Phe Pro Phe Ile Pro Ile Gln Val Lys Gln Leu Leu Ala Gln Val  
               
               
                              40                  45                  50  
               
               
                   
               
               
                 cgg cag gcc agc cag gtg ggc gtg gcc gtg ctg ggc acc tgg tgc cac      306  
               
               
                 Arg Gln Ala Ser Gln Val Gly Val Ala Val Leu Gly Thr Trp Cys His  
               
               
                          55                  60                  65  
               
               
                   
               
               
                 tgc cgg cag gag ccc gag gag agc ctg ggc cgc ttc ctg gag agc ctg      354  
               
               
                 Cys Arg Gln Glu Pro Glu Glu Ser Leu Gly Arg Phe Leu Glu Ser Leu  
               
               
                      70                  75                  80  
               
               
                   
               
               
                 ggt gct gtc ttc ccc cat gag ccc tgg ctg cgg ctg tgc cgg gag aga      402  
               
               
                 Gly Ala Val Phe Pro His Glu Pro Trp Leu Arg Leu Cys Arg Glu Arg  
               
               
                  85                  90                  95                 100  
               
               
                   
               
               
                 ggc ggc acg ttc tgg agc tgc gag gcc acc cac cgg caa gcg ccc act      450  
               
               
                 Gly Gly Thr Phe Trp Ser Cys Glu Ala Thr His Arg Gln Ala Pro Thr  
               
               
                                 105                 110                 115  
               
               
                   
               
               
                 gcc ccc ggt gcc cct ggt gag gac cag gtc atg ctc atc ttc tat gac      498  
               
               
                 Ala Pro Gly Ala Pro Gly Glu Asp Gln Val Met Leu Ile Phe Tyr Asp  
               
               
                             120                 125                 130  
               
               
                   
               
               
                 cag cgc cag gtg ttg ctg tca cag cta cac ctg ccc acc gtc ctg ccc      546  
               
               
                 Gln Arg Gln Val Leu Leu Ser Gln Leu His Leu Pro Thr Val Leu Pro  
               
               
                         135                 140                 145  
               
               
                   
               
               
                 gac cgc cag gct gga gcc acc act gcc agc acg ggg ggc ctg gct gcc      594  
               
               
                 Asp Arg Gln Ala Gly Ala Thr Thr Ala Ser Thr Gly Gly Leu Ala Ala  
               
               
                     150                 155                 160  
               
               
                   
               
               
                 gtc ttc gac acg gta gca cgc agt gag gtg ctc ttc cgc agt gac cgc      642  
               
               
                 Val Phe Asp Thr Val Ala Arg Ser Glu Val Leu Phe Arg Ser Asp Arg  
               
               
                 165                 170                 175                 180  
               
               
                   
               
               
                 ttt gat gag ggc ccc gtg cgg ctg agc cac tgg cag tcg gag ggc gtg      690  
               
               
                 Phe Asp Glu Gly Pro Val Arg Leu Ser His Trp Gln Ser Glu Gly Val  
               
               
                                 185                 190                 195  
               
               
                   
               
               
                 gag gcc agc atc ctc gcg gag ctg gcc agg cga gcc tcg gga ccc att      738  
               
               
                 Glu Ala Ser Ile Leu Ala Glu Leu Ala Arg Arg Ala Ser Gly Pro Ile  
               
               
                             200                 205                 210  
               
               
                   
               
               
                 tgt ctg ctg ttg gcc agc ctg ctg tcg ctg gtc tca gct gtc agt gcc      786  
               
               
                 Cys Leu Leu Leu Ala Ser Leu Leu Ser Leu Val Ser Ala Val Ser Ala  
               
               
                         215                 220                 225  
               
               
                   
               
               
                 tgc cga gtg ttc aag ctc tgg ccc ctg tcc ttc ctc ggg agc aaa ctc      834  
               
               
                 Cys Arg Val Phe Lys Leu Trp Pro Leu Ser Phe Leu Gly Ser Lys Leu  
               
               
                     230                 235                 240  
               
               
                   
               
               
                 tcc acg tgc gaa cag ctc cgg cac cgg ctg gag cac ctc acg cta atc      882  
               
               
                 Ser Thr Cys Glu Gln Leu Arg His Arg Leu Glu His Leu Thr Leu Ile  
               
               
                 245                 250                 255                 260  
               
               
                   
               
               
                 ttc agt aca cgg aag gcg gag aac cct gcc cag ctg atg agg aag gcc      930  
               
               
                 Phe Ser Thr Arg Lys Ala Glu Asn Pro Ala Gln Leu Met Arg Lys Ala  
               
               
                                 265                 270                 275  
               
               
                   
               
               
                 aac acg gtg gcc tct gtg ctg ctg gac gtg gcc ctg ggc ctc atg ctg      978  
               
               
                 Asn Thr Val Ala Ser Val Leu Leu Asp Val Ala Leu Gly Leu Met Leu  
               
               
                             280                 285                 290  
               
               
                   
               
               
                 ctg tcc tgg ctc cac ggg aga agc cgc atc ggg cat ctg gcc gac gcc     1026  
               
               
                 Leu Ser Trp Leu His Gly Arg Ser Arg Ile Gly His Leu Ala Asp Ala  
               
               
                         295                 300                 305  
               
               
                   
               
               
                 ctc gtt cct gtg gct gac cac gtg gcc gag gag ctc cag cat ctg ctg     1074  
               
               
                 Leu Val Pro Val Ala Asp His Val Ala Glu Glu Leu Gln His Leu Leu  
               
               
                     310                 315                 320  
               
               
                   
               
               
                 cag tgg ctg atg ggt gct ccc gcc ggg ctc aag atg aac cgt gca ctg     1122  
               
               
                 Gln Trp Leu Met Gly Ala Pro Ala Gly Leu Lys Met Asn Arg Ala Leu  
               
               
                 325                 330                 335                 340  
               
               
                   
               
               
                 gac cag gtg ctg ggc cgc ttc ttc ctc tac cac atc cac ctg tgg atc     1170  
               
               
                 Asp Gln Val Leu Gly Arg Phe Phe Leu Tyr His Ile His Leu Trp Ile  
               
               
                                 345                 350                 355  
               
               
                   
               
               
                 agc tac atc cac ctc atg tcc ccc ttc gtg gag cac atc ctt tgg cac     1218  
               
               
                 Ser Tyr Ile His Leu Met Ser Pro Phe Val Glu His Ile Leu Trp His  
               
               
                             360                 365                 370  
               
               
                   
               
               
                 gtg ggc ctc tcg gcc tgc ctg ggc ctg acg gtg gcc ctg tcc ctc ctc     1266  
               
               
                 Val Gly Leu Ser Ala Cys Leu Gly Leu Thr Val Ala Leu Ser Leu Leu  
               
               
                         375                 380                 385  
               
               
                   
               
               
                 tcg gac att atc gcc ctc ctc acc ttc cac atc tac tgc ttt tac gtc     1314  
               
               
                 Ser Asp Ile Ile Ala Leu Leu Thr Phe His Ile Tyr Cys Phe Tyr Val  
               
               
                     390                 395                 400  
               
               
                   
               
               
                 tat gga gcc agg ctg tac tgc ctg aag atc cat ggc ctg tcc tca ctg     1362  
               
               
                 Tyr Gly Ala Arg Leu Tyr Cys Leu Lys Ile His Gly Leu Ser Ser Leu  
               
               
                 405                 410                 415                 420  
               
               
                   
               
               
                 tgg cgt ctg ttc cgg ggg aag aag tgg aac gtt ctg cgc cag cgc gtg     1410  
               
               
                 Trp Arg Leu Phe Arg Gly Lys Lys Trp Asn Val Leu Arg Gln Arg Val  
               
               
                                 425                 430                 435  
               
               
                   
               
               
                 gac tcc tgt tcc tat gac ctg gac cag ctg ttc atc ggg act ctg ctc     1458  
               
               
                 Asp Ser Cys Ser Tyr Asp Leu Asp Gln Leu Phe Ile Gly Thr Leu Leu  
               
               
                             440                 445                 450  
               
               
                   
               
               
                 ttc acc atc ctg ctc ttc ctc ctg cct acc aca gcc ctg tac tac ctg     1506  
               
               
                 Phe Thr Ile Leu Leu Phe Leu Leu Pro Thr Thr Ala Leu Tyr Tyr Leu  
               
               
                         455                 460                 465  
               
               
                   
               
               
                 gtg ttc acc ctg ctc cgg ctc ctg gtg gtc gcc gtg cag ggc ctg atc     1554  
               
               
                 Val Phe Thr Leu Leu Arg Leu Leu Val Val Ala Val Gln Gly Leu Ile  
               
               
                     470                 475                 480  
               
               
                   
               
               
                 cat ctg ctg gtg gac ctc atc aac tcc ctg ccg ctg tac tca ctg ggt     1602  
               
               
                 His Leu Leu Val Asp Leu Ile Asn Ser Leu Pro Leu Tyr Ser Leu Gly  
               
               
                 485                 490                 495                 500  
               
               
                   
               
               
                 ctt cgg ctc tgc cgg ccc tac agg ctg gcg gct ggc gtg aag ttc cgt     1650  
               
               
                 Leu Arg Leu Cys Arg Pro Tyr Arg Leu Ala Ala Gly Val Lys Phe Arg  
               
               
                                 505                 510                 515  
               
               
                   
               
               
                 gtc ctc cgg cac gag gcc agc agg ccc ctc cgc ctc ctg atg cag ata     1698  
               
               
                 Val Leu Arg His Glu Ala Ser Arg Pro Leu Arg Leu Leu Met Gln Ile  
               
               
                             520                 525                 530  
               
               
                   
               
               
                 aac cca ctg ccc tac agc cgc gtg gtg cac acc tac cgc ctc ccc agc     1746  
               
               
                 Asn Pro Leu Pro Tyr Ser Arg Val Val His Thr Tyr Arg Leu Pro Ser  
               
               
                         535                 540                 545  
               
               
                   
               
               
                 tgt ggc tgc cac ccc aag cac tcc tgg ggc gcc ctg tgc cgc aag ctg     1794  
               
               
                 Cys Gly Cys His Pro Lys His Ser Trp Gly Ala Leu Cys Arg Lys Leu  
               
               
                     550                 555                 560  
               
               
                   
               
               
                 ttc ctt ggg gag ctc atc tac ccc tgg agg cag aga ggg gac aag cag     1842  
               
               
                 Phe Leu Gly Glu Leu Ile Tyr Pro Trp Arg Gln Arg Gly Asp Lys Gln  
               
               
                 565                 570                 575                 580  
               
               
                   
               
               
                 gac tga gggaactgct ggctcgcctg gcaccaccac acggccacag ccagccatct      1898  
               
               
                 Asp  *  
               
               
                   
               
               
                 gctctgccag ggtggcacca gctcagctgg cgcatgtccc gtgctttgtg gacgctgctg   1958  
               
               
                   
               
               
                 tgtgctcctg aacacggcag gccctgctat cacaccttgg gcttggaggt cattgggagt   2018  
               
               
                   
               
               
                 gagcagatgt gggggtggcc agccaggctg gccgcactcc atcactggca ctgcctgcct   2078  
               
               
                   
               
               
                 tgggacccgc ttcccacctg ctgcggtcac catggtggcg agcacagcaa ccccaggtgt   2138  
               
               
                   
               
               
                 ccagagcact gccccatgcc caccctgcat acccaggtcc agagggtccg tccaccacag   2198  
               
               
                   
               
               
                 cagccccagg tggagggctg gtctccctgg gggctcccca gtggctctgc cctggctgtg   2258  
               
               
                   
               
               
                 ggggtggagg gaccttgcca ggatgaaccc tccagtccca ggcaccctct agctccctca   2318  
               
               
                   
               
               
                 gccgaacagc accctgcatc tgggggattg aagcagtcgc tgacccccgt ccccagcggg   2378  
               
               
                   
               
               
                 cccgggccct cactccctga accacacggg gtttatttgc ggatgttccc tggagaggtc   2438  
               
               
                   
               
               
                 gctttgtgaa gaaaccatca gcaggctgtg agcatcgcca ggctgctgtg ggggcgggag   2498  
               
               
                   
               
               
                 cagcctcagt gtcaagggcc tgcccactga cccagccgta cctattcgtc cacggtgccc   2558  
               
               
                   
               
               
                 cgtagcagca ggtcctgcgg ccaaatctgt ctcccttcat gggcctccca gggaaggagg   2618  
               
               
                   
               
               
                 aagccctgct gtgcagacac ctctgtggcc ccccaggggt gtgagcggcc tggggagggg   2678  
               
               
                   
               
               
                 gccgtggcac tgaggccgaa agtgcctgcc agacggcacg gtctgggtgc gggtgttccc   2738  
               
               
                   
               
               
                 tgtgagcccg agtccgcttc aggaggggag cctgcaggtg ccggctggtg aggggatgac   2798  
               
               
                   
               
               
                 gcgctgtggg tgggaggagg cagcgcccat ctcagcagca ccaggactgc ctgggactcc   2858  
               
               
                   
               
               
                 ctggcaaccc agcaccgggg aagccgtcag ctgctgtgac aataaaacct gccccgtgtc   2918  
               
               
                   
               
               
                 tgg                                                                 2921  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 7  
               
               
                 &lt;211&gt; LENGTH: 581  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo Sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 7  
               
               
                   
               
               
                 Met Val Leu Lys Ala Phe Phe Pro Thr Cys Cys Val Ser Ala Asp Ser  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gly Leu Leu Val Gly Arg Trp Val Pro Glu Gln Ser Ser Ala Val Val  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Leu Ala Val Leu His Phe Pro Phe Ile Pro Ile Gln Val Lys Gln Leu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Ala Gln Val Arg Gln Ala Ser Gln Val Gly Val Ala Val Leu Gly  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Thr Trp Cys His Cys Arg Gln Glu Pro Glu Glu Ser Leu Gly Arg Phe  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Leu Glu Ser Leu Gly Ala Val Phe Pro His Glu Pro Trp Leu Arg Leu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Cys Arg Glu Arg Gly Gly Thr Phe Trp Ser Cys Glu Ala Thr His Arg  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Gln Ala Pro Thr Ala Pro Gly Ala Pro Gly Glu Asp Gln Val Met Leu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ile Phe Tyr Asp Gln Arg Gln Val Leu Leu Ser Gln Leu His Leu Pro  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Thr Val Leu Pro Asp Arg Gln Ala Gly Ala Thr Thr Ala Ser Thr Gly  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Gly Leu Ala Ala Val Phe Asp Thr Val Ala Arg Ser Glu Val Leu Phe  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Arg Ser Asp Arg Phe Asp Glu Gly Pro Val Arg Leu Ser His Trp Gln  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ser Glu Gly Val Glu Ala Ser Ile Leu Ala Glu Leu Ala Arg Arg Ala  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ser Gly Pro Ile Cys Leu Leu Leu Ala Ser Leu Leu Ser Leu Val Ser  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ala Val Ser Ala Cys Arg Val Phe Lys Leu Trp Pro Leu Ser Phe Leu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Gly Ser Lys Leu Ser Thr Cys Glu Gln Leu Arg His Arg Leu Glu His  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Leu Thr Leu Ile Phe Ser Thr Arg Lys Ala Glu Asn Pro Ala Gln Leu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Met Arg Lys Ala Asn Thr Val Ala Ser Val Leu Leu Asp Val Ala Leu  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Gly Leu Met Leu Leu Ser Trp Leu His Gly Arg Ser Arg Ile Gly His  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Leu Ala Asp Ala Leu Val Pro Val Ala Asp His Val Ala Glu Glu Leu  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gln His Leu Leu Gln Trp Leu Met Gly Ala Pro Ala Gly Leu Lys Met  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Asn Arg Ala Leu Asp Gln Val Leu Gly Arg Phe Phe Leu Tyr His Ile  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 His Leu Trp Ile Ser Tyr Ile His Leu Met Ser Pro Phe Val Glu His  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Ile Leu Trp His Val Gly Leu Ser Ala Cys Leu Gly Leu Thr Val Ala  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Leu Ser Leu Leu Ser Asp Ile Ile Ala Leu Leu Thr Phe His Ile Tyr  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Cys Phe Tyr Val Tyr Gly Ala Arg Leu Tyr Cys Leu Lys Ile His Gly  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Leu Ser Ser Leu Trp Arg Leu Phe Arg Gly Lys Lys Trp Asn Val Leu  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Arg Gln Arg Val Asp Ser Cys Ser Tyr Asp Leu Asp Gln Leu Phe Ile  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Gly Thr Leu Leu Phe Thr Ile Leu Leu Phe Leu Leu Pro Thr Thr Ala  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Leu Tyr Tyr Leu Val Phe Thr Leu Leu Arg Leu Leu Val Val Ala Val  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Gln Gly Leu Ile His Leu Leu Val Asp Leu Ile Asn Ser Leu Pro Leu  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Tyr Ser Leu Gly Leu Arg Leu Cys Arg Pro Tyr Arg Leu Ala Ala Gly  
               
               
                             500                 505                 510  
               
               
                   
               
               
                 Val Lys Phe Arg Val Leu Arg His Glu Ala Ser Arg Pro Leu Arg Leu  
               
               
                         515                 520                 525  
               
               
                   
               
               
                 Leu Met Gln Ile Asn Pro Leu Pro Tyr Ser Arg Val Val His Thr Tyr  
               
               
                     530                 535                 540  
               
               
                   
               
               
                 Arg Leu Pro Ser Cys Gly Cys His Pro Lys His Ser Trp Gly Ala Leu  
               
               
                 545                 550                 555                 560  
               
               
                   
               
               
                 Cys Arg Lys Leu Phe Leu Gly Glu Leu Ile Tyr Pro Trp Arg Gln Arg  
               
               
                                 565                 570                 575  
               
               
                   
               
               
                 Gly Asp Lys Gln Asp  
               
               
                             580  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 8  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: PCR primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 8  
               
               
                   
               
               
                 agcagggctt cctccttc                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 9  
               
               
                 &lt;211&gt; LENGTH: 43  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: PCR primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 9  
               
               
                   
               
               
                 agcggataac aatttcacac aggtgaccca gccgtaccta ttc                       43  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 10  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: MassExtend primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 10  
               
               
                   
               
               
                 aagggagaca gatttggc                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 11  
               
               
                 &lt;211&gt; LENGTH: 1790  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (131)...(1612)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding Cholesterol ester  
               
               
                       transfer protein (CETP)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 11  
               
               
                   
               
               
                 gtgaatctct ggggccagga agaccctgct gcccggaaga gcctcatgtt ccgtgggggc     60  
               
               
                   
               
               
                 tgggcggaca tacatatacg ggctccaggc tgaacggctc gggccactta cacaccactg    120  
               
               
                   
               
               
                 cctgataacc atg ctg gct gcc aca gtc ctg acc ctg gcc ctg ctg ggc       169  
               
               
                            Met Leu Ala Ala Thr Val Leu Thr Leu Ala Leu Leu Gly  
               
               
                              1               5                   10  
               
               
                   
               
               
                 aat gcc cat gcc tgc tcc aaa ggc acc tcg cac gag gca ggc atc gtg      217  
               
               
                 Asn Ala His Ala Cys Ser Lys Gly Thr Ser His Glu Ala Gly Ile Val  
               
               
                      15                  20                  25  
               
               
                   
               
               
                 tgc cgc atc acc aag cct gcc ctc ctg gtg ttg aac cac gag act gcc      265  
               
               
                 Cys Arg Ile Thr Lys Pro Ala Leu Leu Val Leu Asn His Glu Thr Ala  
               
               
                  30                  35                  40                  45  
               
               
                   
               
               
                 aag gtg atc cag acc gcc ttc cag cga gcc agc tac cca gat atc acg      313  
               
               
                 Lys Val Ile Gln Thr Ala Phe Gln Arg Ala Ser Tyr Pro Asp Ile Thr  
               
               
                                  50                  55                  60  
               
               
                   
               
               
                 ggc gag aag gcc atg atg ctc ctt ggc caa gtc aag tat ggg ttg cac      361  
               
               
                 Gly Glu Lys Ala Met Met Leu Leu Gly Gln Val Lys Tyr Gly Leu His  
               
               
                              65                  70                  75  
               
               
                   
               
               
                 aac atc cag atc agc cac ttg tcc atc gcc agc agc cag gtg gag ctg      409  
               
               
                 Asn Ile Gln Ile Ser His Leu Ser Ile Ala Ser Ser Gln Val Glu Leu  
               
               
                          80                  85                  90  
               
               
                   
               
               
                 gtg gaa gcc aag tcc att gat gtc tcc att cag aac gtg tct gtg gtc      457  
               
               
                 Val Glu Ala Lys Ser Ile Asp Val Ser Ile Gln Asn Val Ser Val Val  
               
               
                      95                 100                 105  
               
               
                   
               
               
                 ttc aag ggg acc ctg aag tat ggc tac acc act gcc tgg tgg ctg ggt      505  
               
               
                 Phe Lys Gly Thr Leu Lys Tyr Gly Tyr Thr Thr Ala Trp Trp Leu Gly  
               
               
                 110                 115                 120                 125  
               
               
                   
               
               
                 att gat cag tcc att gac ttc gag atc gac tct gcc att gac ctc cag      553  
               
               
                 Ile Asp Gln Ser Ile Asp Phe Glu Ile Asp Ser Ala Ile Asp Leu Gln  
               
               
                                 130                 135                 140  
               
               
                   
               
               
                 atc aac aca cag ctg acc tgt gac tct ggt aga gtg cgg acc gat gcc      601  
               
               
                 Ile Asn Thr Gln Leu Thr Cys Asp Ser Gly Arg Val Arg Thr Asp Ala  
               
               
                             145                 150                 155  
               
               
                   
               
               
                 cct gac tgc tac ctg tct ttc cat aag ctg ctc ctg cat ctc caa ggg      649  
               
               
                 Pro Asp Cys Tyr Leu Ser Phe His Lys Leu Leu Leu His Leu Gln Gly  
               
               
                         160                 165                 170  
               
               
                   
               
               
                 gag cga gag cct ggg tgg atc aag cag ctg ttc aca aat ttc atc tcc      697  
               
               
                 Glu Arg Glu Pro Gly Trp Ile Lys Gln Leu Phe Thr Asn Phe Ile Ser  
               
               
                     175                 180                 185  
               
               
                   
               
               
                 ttc acc ctg aag ctg gtc ctg aag gga cag atc tgc aaa gag atc aac      745  
               
               
                 Phe Thr Leu Lys Leu Val Leu Lys Gly Gln Ile Cys Lys Glu Ile Asn  
               
               
                 190                 195                 200                 205  
               
               
                   
               
               
                 gtc atc tct aac atc atg gcc gat ttt gtc cag aca agg gct gcc agc      793  
               
               
                 Val Ile Ser Asn Ile Met Ala Asp Phe Val Gln Thr Arg Ala Ala Ser  
               
               
                                 210                 215                 220  
               
               
                   
               
               
                 atc ctt tca gat gga gac att ggg gtg gac att tcc ctg aca ggt gat      841  
               
               
                 Ile Leu Ser Asp Gly Asp Ile Gly Val Asp Ile Ser Leu Thr Gly Asp  
               
               
                             225                 230                 235  
               
               
                   
               
               
                 ccc gtc atc aca gcc tcc tac ctg gag tcc cat cac aag ggt cat ttc      889  
               
               
                 Pro Val Ile Thr Ala Ser Tyr Leu Glu Ser His His Lys Gly His Phe  
               
               
                         240                 245                 250  
               
               
                   
               
               
                 atc tac aag aat gtc tca gag gac ctc ccc ctc ccc acc ttc tcg ccc      937  
               
               
                 Ile Tyr Lys Asn Val Ser Glu Asp Leu Pro Leu Pro Thr Phe Ser Pro  
               
               
                     255                 260                 265  
               
               
                   
               
               
                 aca ctg ctg ggg gac tcc cgc atg ctg tac ttc tgg ttc tct gag cga      985  
               
               
                 Thr Leu Leu Gly Asp Ser Arg Met Leu Tyr Phe Trp Phe Ser Glu Arg  
               
               
                 270                 275                 280                 285  
               
               
                   
               
               
                 gtc ttc cac tcg ctg gcc aag gta gct ttc cag gat ggc cgc ctc atg     1033  
               
               
                 Val Phe His Ser Leu Ala Lys Val Ala Phe Gln Asp Gly Arg Leu Met  
               
               
                                 290                 295                 300  
               
               
                   
               
               
                 ctc agc ctg atg gga gac gag ttc aag gca gtg ctg gag acc tgg ggc     1081  
               
               
                 Leu Ser Leu Met Gly Asp Glu Phe Lys Ala Val Leu Glu Thr Trp Gly  
               
               
                             305                 310                 315  
               
               
                   
               
               
                 ttc aac acc aac cag gaa atc ttc caa gag gtt gtc ggc ggc ttc ccc     1129  
               
               
                 Phe Asn Thr Asn Gln Glu Ile Phe Gln Glu Val Val Gly Gly Phe Pro  
               
               
                         320                 325                 330  
               
               
                   
               
               
                 agc cag gcc caa gtc acc gtc cac tgc ctc aag atg ccc aag atc tcc     1177  
               
               
                 Ser Gln Ala Gln Val Thr Val His Cys Leu Lys Met Pro Lys Ile Ser  
               
               
                     335                 340                 345  
               
               
                   
               
               
                 tgc caa aac aag gga gtc gtg gtc aat tct tca gtg atg gtg aaa ttc     1225  
               
               
                 Cys Gln Asn Lys Gly Val Val Val Asn Ser Ser Val Met Val Lys Phe  
               
               
                 350                 355                 360                 365  
               
               
                   
               
               
                 ctc ttt cca cgc cca gac cag caa cat tct gta gct tac aca ttt gaa     1273  
               
               
                 Leu Phe Pro Arg Pro Asp Gln Gln His Ser Val Ala Tyr Thr Phe Glu  
               
               
                                 370                 375                 380  
               
               
                   
               
               
                 gag gat atc gtg act acc gtc cag gcc tcc tat tct aag aaa aag ctc     1321  
               
               
                 Glu Asp Ile Val Thr Thr Val Gln Ala Ser Tyr Ser Lys Lys Lys Leu  
               
               
                             385                 390                 395  
               
               
                   
               
               
                 ttc tta agc ctc ttg gat ttc cag att aca cca aag act gtt tcc aac     1369  
               
               
                 Phe Leu Ser Leu Leu Asp Phe Gln Ile Thr Pro Lys Thr Val Ser Asn  
               
               
                         400                 405                 410  
               
               
                   
               
               
                 ttg act gag agc agc tcc gag tcc atc cag agc ttc ctg cag tca atg     1417  
               
               
                 Leu Thr Glu Ser Ser Ser Glu Ser Ile Gln Ser Phe Leu Gln Ser Met  
               
               
                     415                 420                 425  
               
               
                   
               
               
                 atc acc gct gtg ggc atc cct gag gtc atg tct cgg ctc gag gta gtg     1465  
               
               
                 Ile Thr Ala Val Gly Ile Pro Glu Val Met Ser Arg Leu Glu Val Val  
               
               
                 430                 435                 440                 445  
               
               
                   
               
               
                 ttt aca gcc ctc atg aac agc aaa ggc gtg agc ctc ttc gac atc atc     1513  
               
               
                 Phe Thr Ala Leu Met Asn Ser Lys Gly Val Ser Leu Phe Asp Ile Ile  
               
               
                                 450                 455                 460  
               
               
                   
               
               
                 aac cct gag att atc act cga gat ggc ttc ctg ctg ctg cag atg gac     1561  
               
               
                 Asn Pro Glu Ile Ile Thr Arg Asp Gly Phe Leu Leu Leu Gln Met Asp  
               
               
                             465                 470                 475  
               
               
                   
               
               
                 ttt ggc ttc cct gag cac ctg ctg gtg gat ttc ctc cag agc ttg agc     1609  
               
               
                 Phe Gly Phe Pro Glu His Leu Leu Val Asp Phe Leu Gln Ser Leu Ser  
               
               
                         480                 485                 490  
               
               
                   
               
               
                 tag aagtctccaa ggaggtcggg atggggcttg tagcagaagg caagcaccag          1662  
               
               
                   
               
               
                 gctcacagct ggaaccctgg tgtctcctcc agcgtggtgg aagttgggtt aggagtacgg   1722  
               
               
                   
               
               
                 agatggagat tggctcccaa ctcctcccta tcctaaaggc ccactggcat taaagtgctg   1782  
               
               
                   
               
               
                 tatccaag                                                            1790  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 12  
               
               
                 &lt;211&gt; LENGTH: 493  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 12  
               
               
                   
               
               
                 Met Leu Ala Ala Thr Val Leu Thr Leu Ala Leu Leu Gly Asn Ala His  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Ala Cys Ser Lys Gly Thr Ser His Glu Ala Gly Ile Val Cys Arg Ile  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Thr Lys Pro Ala Leu Leu Val Leu Asn His Glu Thr Ala Lys Val Ile  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gln Thr Ala Phe Gln Arg Ala Ser Tyr Pro Asp Ile Thr Gly Glu Lys  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ala Met Met Leu Leu Gly Gln Val Lys Tyr Gly Leu His Asn Ile Gln  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ile Ser His Leu Ser Ile Ala Ser Ser Gln Val Glu Leu Val Glu Ala  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Lys Ser Ile Asp Val Ser Ile Gln Asn Val Ser Val Val Phe Lys Gly  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Thr Leu Lys Tyr Gly Tyr Thr Thr Ala Trp Trp Leu Gly Ile Asp Gln  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ser Ile Asp Phe Glu Ile Asp Ser Ala Ile Asp Leu Gln Ile Asn Thr  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Gln Leu Thr Cys Asp Ser Gly Arg Val Arg Thr Asp Ala Pro Asp Cys  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Tyr Leu Ser Phe His Lys Leu Leu Leu His Leu Gln Gly Glu Arg Glu  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Pro Gly Trp Ile Lys Gln Leu Phe Thr Asn Phe Ile Ser Phe Thr Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Lys Leu Val Leu Lys Gly Gln Ile Cys Lys Glu Ile Asn Val Ile Ser  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Asn Ile Met Ala Asp Phe Val Gln Thr Arg Ala Ala Ser Ile Leu Ser  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Asp Gly Asp Ile Gly Val Asp Ile Ser Leu Thr Gly Asp Pro Val Ile  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Thr Ala Ser Tyr Leu Glu Ser His His Lys Gly His Phe Ile Tyr Lys  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Asn Val Ser Glu Asp Leu Pro Leu Pro Thr Phe Ser Pro Thr Leu Leu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Gly Asp Ser Arg Met Leu Tyr Phe Trp Phe Ser Glu Arg Val Phe His  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Ser Leu Ala Lys Val Ala Phe Gln Asp Gly Arg Leu Met Leu Ser Leu  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Met Gly Asp Glu Phe Lys Ala Val Leu Glu Thr Trp Gly Phe Asn Thr  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Asn Gln Glu Ile Phe Gln Glu Val Val Gly Gly Phe Pro Ser Gln Ala  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Gln Val Thr Val His Cys Leu Lys Met Pro Lys Ile Ser Cys Gln Asn  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Lys Gly Val Val Val Asn Ser Ser Val Met Val Lys Phe Leu Phe Pro  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Arg Pro Asp Gln Gln His Ser Val Ala Tyr Thr Phe Glu Glu Asp Ile  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Val Thr Thr Val Gln Ala Ser Tyr Ser Lys Lys Lys Leu Phe Leu Ser  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Leu Leu Asp Phe Gln Ile Thr Pro Lys Thr Val Ser Asn Leu Thr Glu  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Ser Ser Ser Glu Ser Ile Gln Ser Phe Leu Gln Ser Met Ile Thr Ala  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Val Gly Ile Pro Glu Val Met Ser Arg Leu Glu Val Val Phe Thr Ala  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Leu Met Asn Ser Lys Gly Val Ser Leu Phe Asp Ile Ile Asn Pro Glu  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Ile Ile Thr Arg Asp Gly Phe Leu Leu Leu Gln Met Asp Phe Gly Phe  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Pro Glu His Leu Leu Val Asp Phe Leu Gln Ser Leu Ser  
               
               
                                 485                 490  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 13  
               
               
                 &lt;211&gt; LENGTH: 3549  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (175)...(1602)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding lipoprotein lipase  
               
               
                       (LPL)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 13  
               
               
                   
               
               
                 cccctcttcc tcctcctcaa gggaaagctg cccacttcta gctgccctgc catccccttt     60  
               
               
                   
               
               
                 aaagggcgac ttgctcagcg ccaaaccgcg gctccagccc tctccagcct ccggctcagc    120  
               
               
                   
               
               
                 cggctcatca gtcggtccgc gccttgcagc tcctccagag ggacgcgccc cgag atg      177  
               
               
                                                                             Met  
               
               
                                                                              1  
               
               
                   
               
               
                 gag agc aaa gcc ctg ctc gtg ctg act ctg gcc gtg tgg ctc cag agt      225  
               
               
                 Glu Ser Lys Ala Leu Leu Val Leu Thr Leu Ala Val Trp Leu Gln Ser  
               
               
                              5                   10                  15  
               
               
                   
               
               
                 ctg acc gcc tcc cgc gga ggg gtg gcc gcc gcc gac caa aga aga gat      273  
               
               
                 Leu Thr Ala Ser Arg Gly Gly Val Ala Ala Ala Asp Gln Arg Arg Asp  
               
               
                          20                  25                  30  
               
               
                   
               
               
                 ttt atc gac atc gaa agt aaa ttt gcc cta agg acc cct gaa gac aca      321  
               
               
                 Phe Ile Asp Ile Glu Ser Lys Phe Ala Leu Arg Thr Pro Glu Asp Thr  
               
               
                      35                  40                  45  
               
               
                   
               
               
                 gct gag gac act tgc cac ctc att ccc gga gta gca gag tcc gtg gct      369  
               
               
                 Ala Glu Asp Thr Cys His Leu Ile Pro Gly Val Ala Glu Ser Val Ala  
               
               
                  50                  55                  60                  65  
               
               
                   
               
               
                 acc tgt cat ttc aat cac agc agc aaa acc ttc atg gtg atc cat ggc      417  
               
               
                 Thr Cys His Phe Asn His Ser Ser Lys Thr Phe Met Val Ile His Gly  
               
               
                                  70                  75                  80  
               
               
                   
               
               
                 tgg acg gta aca gga atg tat gag agt tgg gtg cca aaa ctt gtg gcc      465  
               
               
                 Trp Thr Val Thr Gly Met Tyr Glu Ser Trp Val Pro Lys Leu Val Ala  
               
               
                              85                  90                  95  
               
               
                   
               
               
                 gcc ctg tac aag aga gaa cca gac tcc aat gtc att gtg gtg gac tgg      513  
               
               
                 Ala Leu Tyr Lys Arg Glu Pro Asp Ser Asn Val Ile Val Val Asp Trp  
               
               
                         100                 105                 110  
               
               
                   
               
               
                 ctg tca cgg gct cag gag cat tac cca gtg tcc gcg ggc tac acc aaa      561  
               
               
                 Leu Ser Arg Ala Gln Glu His Tyr Pro Val Ser Ala Gly Tyr Thr Lys  
               
               
                     115                 120                 125  
               
               
                   
               
               
                 ctg gtg gga cag gat gtg gcc cgg ttt atc aac tgg atg gag gag gag      609  
               
               
                 Leu Val Gly Gln Asp Val Ala Arg Phe Ile Asn Trp Met Glu Glu Glu  
               
               
                 130                 135                 140                 145  
               
               
                   
               
               
                 ttt aac tac cct ctg gac aat gtc cat ctc ttg gga tac agc ctt gga      657  
               
               
                 Phe Asn Tyr Pro Leu Asp Asn Val His Leu Leu Gly Tyr Ser Leu Gly  
               
               
                                 150                 155                 160  
               
               
                   
               
               
                 gcc cat gct gct ggc att gca gga agt ctg acc aat aag aaa gtc aac      705  
               
               
                 Ala His Ala Ala Gly Ile Ala Gly Ser Leu Thr Asn Lys Lys Val Asn  
               
               
                             165                 170                 175  
               
               
                   
               
               
                 aga att act ggc ctc gat cca gct gga cct aac ttt gag tat gca gaa      753  
               
               
                 Arg Ile Thr Gly Leu Asp Pro Ala Gly Pro Asn Phe Glu Tyr Ala Glu  
               
               
                         180                 185                 190  
               
               
                   
               
               
                 gcc ccg agt cgt ctt tct cct gat gat gca gat ttt gta gac gtc tta      801  
               
               
                 Ala Pro Ser Arg Leu Ser Pro Asp Asp Ala Asp Phe Val Asp Val Leu  
               
               
                     195                 200                 205  
               
               
                   
               
               
                 cac aca ttc acc aga ggg tcc cct ggt cga agc att gga atc cag aaa      849  
               
               
                 His Thr Phe Thr Arg Gly Ser Pro Gly Arg Ser Ile Gly Ile Gln Lys  
               
               
                 210                 215                 220                 225  
               
               
                   
               
               
                 cca gtt ggg cat gtt gac att tac ccg aat gga ggt act ttt cag cca      897  
               
               
                 Pro Val Gly His Val Asp Ile Tyr Pro Asn Gly Gly Thr Phe Gln Pro  
               
               
                                 230                 235                 240  
               
               
                   
               
               
                 gga tgt aac att gga gaa gct atc cgc gtg att gca gag aga gga ctt      945  
               
               
                 Gly Cys Asn Ile Gly Glu Ala Ile Arg Val Ile Ala Glu Arg Gly Leu  
               
               
                             245                 250                 255  
               
               
                   
               
               
                 gga gat gtg gac cag cta gtg aag tgc tcc cac gag cgc tcc att cat      993  
               
               
                 Gly Asp Val Asp Gln Leu Val Lys Cys Ser His Glu Arg Ser Ile His  
               
               
                         260                 265                 270  
               
               
                   
               
               
                 ctc ttc atc gac tct ctg ttg aat gaa gaa aat cca agt aag gcc tac     1041  
               
               
                 Leu Phe Ile Asp Ser Leu Leu Asn Glu Glu Asn Pro Ser Lys Ala Tyr  
               
               
                     275                 280                 285  
               
               
                   
               
               
                 agg tgc agt tcc aag gaa gcc ttt gag aaa ggg ctc tgc ttg agt tgt     1089  
               
               
                 Arg Cys Ser Ser Lys Glu Ala Phe Glu Lys Gly Leu Cys Leu Ser Cys  
               
               
                 290                 295                 300                 305  
               
               
                   
               
               
                 aga aag aac cgc tgc aac aat ctg ggc tat gag atc aat aaa gtc aga     1137  
               
               
                 Arg Lys Asn Arg Cys Asn Asn Leu Gly Tyr Glu Ile Asn Lys Val Arg  
               
               
                                 310                 315                 320  
               
               
                   
               
               
                 gcc aaa aga agc agc aaa atg tac ctg aag act cgt tct cag atg ccc     1185  
               
               
                 Ala Lys Arg Ser Ser Lys Met Tyr Leu Lys Thr Arg Ser Gln Met Pro  
               
               
                             325                 330                 335  
               
               
                   
               
               
                 tac aaa gtc ttc cat tac caa gta aag att cat ttt tct ggg act gag     1233  
               
               
                 Tyr Lys Val Phe His Tyr Gln Val Lys Ile His Phe Ser Gly Thr Glu  
               
               
                         340                 345                 350  
               
               
                   
               
               
                 agt gaa acc cat acc aat cag gcc ttt gag att tct ctg tat ggc acc     1281  
               
               
                 Ser Glu Thr His Thr Asn Gln Ala Phe Glu Ile Ser Leu Tyr Gly Thr  
               
               
                     355                 360                 365  
               
               
                   
               
               
                 gtg gcc gag agt gag aac atc cca ttc act ctg cct gaa gtt tcc aca     1329  
               
               
                 Val Ala Glu Ser Glu Asn Ile Pro Phe Thr Leu Pro Glu Val Ser Thr  
               
               
                 370                 375                 380                 385  
               
               
                   
               
               
                 aat aag acc tac tcc ttc cta att tac aca gag gta gat att gga gaa     1377  
               
               
                 Asn Lys Thr Tyr Ser Phe Leu Ile Tyr Thr Glu Val Asp Ile Gly Glu  
               
               
                                 390                 395                 400  
               
               
                   
               
               
                 cta ctc atg ttg aag ctc aaa tgg aag agt gat tca tac ttt agc tgg     1425  
               
               
                 Leu Leu Met Leu Lys Leu Lys Trp Lys Ser Asp Ser Tyr Phe Ser Trp  
               
               
                             405                 410                 415  
               
               
                   
               
               
                 tca gac tgg tgg agc agt ccc ggc ttc gcc att cag aag atc aga gta     1473  
               
               
                 Ser Asp Trp Trp Ser Ser Pro Gly Phe Ala Ile Gln Lys Ile Arg Val  
               
               
                         420                 425                 430  
               
               
                   
               
               
                 aaa gca gga gag act cag aaa aag gtg atc ttc tgt tct agg gag aaa     1521  
               
               
                 Lys Ala Gly Glu Thr Gln Lys Lys Val Ile Phe Cys Ser Arg Glu Lys  
               
               
                     435                 440                 445  
               
               
                   
               
               
                 gtg tct cat ttg cag aaa gga aag gca cct gcg gta ttt gtg aaa tgc     1569  
               
               
                 Val Ser His Leu Gln Lys Gly Lys Ala Pro Ala Val Phe Val Lys Cys  
               
               
                 450                 455                 460                 465  
               
               
                   
               
               
                 cat gac aag tct ctg aat aag aag tca ggc tga aactgggcga atctacagaa   1622  
               
               
                 His Asp Lys Ser Leu Asn Lys Lys Ser Gly  *  
               
               
                                 470                 475  
               
               
                   
               
               
                 caaagaacgg catgtgaatt ctgtgaagaa tgaagtggag gaagtaactt ttacaaaaca   1682  
               
               
                   
               
               
                 tacccagtgt ttggggtgtt tcaaaagtgg attttcctga atattaatcc cagccctacc   1742  
               
               
                   
               
               
                 cttgttagtt attttaggag acagtctcaa gcactaaaaa gtggctaatt caatttatgg   1802  
               
               
                   
               
               
                 ggtatagtgg ccaaatagca catcctccaa cgttaaaaga cagtggatca tgaaaagtgc   1862  
               
               
                   
               
               
                 tgttttgtcc tttgagaaag aaataattgt ttgagcgcag agtaaaataa ggctccttca   1922  
               
               
                   
               
               
                 tgtggcgtat tgggccatag cctataattg gttagaacct cctattttaa ttggaattct   1982  
               
               
                   
               
               
                 ggatctttcg gactgaggcc ttctcaaact ttactctaag tctccaagaa tacagaaaat   2042  
               
               
                   
               
               
                 gcttttccgc ggcacgaatc agactcatct acacagcagt atgaatgatg ttttagaatg   2102  
               
               
                   
               
               
                 attccctctt gctattggaa tgtggtccag acgtcaacca ggaacatgta acttggagag   2162  
               
               
                   
               
               
                 ggacgaagaa agggtctgat aaacacagag gttttaaaca gtccctacca ttggcctgca   2222  
               
               
                   
               
               
                 tcatgacaaa gttacaaatt caaggagata taaaatctag atcaattaat tcttaatagg   2282  
               
               
                   
               
               
                 ctttatcgtt tattgcttaa tccctctctc ccccttcttt tttgtctcaa gattatatta   2342  
               
               
                   
               
               
                 taataatgtt ctctgggtag gtgttgaaaa tgagcctgta atcctcagct gacacataat   2402  
               
               
                   
               
               
                 ttgaatggtg cagaaaaaaa aaagataccg taattttatt attagattct ccaaatgatt   2462  
               
               
                   
               
               
                 ttcatcaatt taaaatcatt caatatctga cagttactct tcagttttag gcttaccttg   2522  
               
               
                   
               
               
                 gtcatgcttc agttgtactt ccagtgcgtc tcttttgttc ctggctttga catgaaaaga   2582  
               
               
                   
               
               
                 taggtttgag ttcaaatttt gcattgtgtg agcttctaca gattttagac aaggaccgtt   2642  
               
               
                   
               
               
                 tttactaagt aaaagggtgg agaggttcct ggggtggatt cctaagcagt gcttgtaaac   2702  
               
               
                   
               
               
                 catcgcgtgc aatgagccag atggagtacc atgagggttg ttatttgttg tttttaacaa   2762  
               
               
                   
               
               
                 ctaatcaaga gtgagtgaac aactatttat aaactagatc tcctattttt cagaatgctc   2822  
               
               
                   
               
               
                 ttctacgtat aaatatgaaa tgataaagat gtcaaatatc tcagaggcta tagctgggaa   2882  
               
               
                   
               
               
                 cccgactgtg aaagtatgtg atatctgaac acatactaga aagctctgca tgtgtgttgt   2942  
               
               
                   
               
               
                 ccttcagcat aattcggaag ggaaaacagt cgatcaaggg atgtattgga acatgtcgga   3002  
               
               
                   
               
               
                 gtagaaattg ttcctgatgt gccagaactt cgaccctttc tctgagagag atgatcgtgc   3062  
               
               
                   
               
               
                 ctataaatag taggaccaat gttgtgatta acatcatcag gcttggaatg aattctctct   3122  
               
               
                   
               
               
                 aaaaataaaa tgatgtatga tttgttgttg gcatcccctt tattaattca ttaaatttct   3182  
               
               
                   
               
               
                 ggatttgggt tgtgacccag ggtgcattaa cttaaaagat tcactaaagc agcacatagc   3242  
               
               
                   
               
               
                 actgggaact ctggctccga aaaactttgt tatatatatc aaggatgttc tggctttaca   3302  
               
               
                   
               
               
                 ttttatttat tagctgtaaa tacatgtgtg gatgtgtaaa tggagcttgt acatattgga   3362  
               
               
                   
               
               
                 aaggtcattg tggctatctg catttataaa tgtgtggtgc taactgtatg tgtctttatc   3422  
               
               
                   
               
               
                 agtgatggtc tcacagagcc aactcactct tatgaaatgg gctttaacaa aacaagaaag   3482  
               
               
                   
               
               
                 aaacgtactt aactgtgtga agaaatggaa tcagctttta ataaaattga caacatttta   3542  
               
               
                   
               
               
                 ttaccac                                                             3549  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 14  
               
               
                 &lt;211&gt; LENGTH: 475  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 14  
               
               
                   
               
               
                 Met Glu Ser Lys Ala Leu Leu Val Leu Thr Leu Ala Val Trp Leu Gln  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Ser Leu Thr Ala Ser Arg Gly Gly Val Ala Ala Ala Asp Gln Arg Arg  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Asp Phe Ile Asp Ile Glu Ser Lys Phe Ala Leu Arg Thr Pro Glu Asp  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Thr Ala Glu Asp Thr Cys His Leu Ile Pro Gly Val Ala Glu Ser Val  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ala Thr Cys His Phe Asn His Ser Ser Lys Thr Phe Met Val Ile His  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Gly Trp Thr Val Thr Gly Met Tyr Glu Ser Trp Val Pro Lys Leu Val  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ala Ala Leu Tyr Lys Arg Glu Pro Asp Ser Asn Val Ile Val Val Asp  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Trp Leu Ser Arg Ala Gln Glu His Tyr Pro Val Ser Ala Gly Tyr Thr  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Lys Leu Val Gly Gln Asp Val Ala Arg Phe Ile Asn Trp Met Glu Glu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Glu Phe Asn Tyr Pro Leu Asp Asn Val His Leu Leu Gly Tyr Ser Leu  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Gly Ala His Ala Ala Gly Ile Ala Gly Ser Leu Thr Asn Lys Lys Val  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Asn Arg Ile Thr Gly Leu Asp Pro Ala Gly Pro Asn Phe Glu Tyr Ala  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Glu Ala Pro Ser Arg Leu Ser Pro Asp Asp Ala Asp Phe Val Asp Val  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu His Thr Phe Thr Arg Gly Ser Pro Gly Arg Ser Ile Gly Ile Gln  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Lys Pro Val Gly His Val Asp Ile Tyr Pro Asn Gly Gly Thr Phe Gln  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Pro Gly Cys Asn Ile Gly Glu Ala Ile Arg Val Ile Ala Glu Arg Gly  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Leu Gly Asp Val Asp Gln Leu Val Lys Cys Ser His Glu Arg Ser Ile  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 His Leu Phe Ile Asp Ser Leu Leu Asn Glu Glu Asn Pro Ser Lys Ala  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Tyr Arg Cys Ser Ser Lys Glu Ala Phe Glu Lys Gly Leu Cys Leu Ser  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Cys Arg Lys Asn Arg Cys Asn Asn Leu Gly Tyr Glu Ile Asn Lys Val  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Arg Ala Lys Arg Ser Ser Lys Met Tyr Leu Lys Thr Arg Ser Gln Met  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Pro Tyr Lys Val Phe His Tyr Gln Val Lys Ile His Phe Ser Gly Thr  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Glu Ser Glu Thr His Thr Asn Gln Ala Phe Glu Ile Ser Leu Tyr Gly  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Thr Val Ala Glu Ser Glu Asn Ile Pro Phe Thr Leu Pro Glu Val Ser  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Thr Asn Lys Thr Tyr Ser Phe Leu Ile Tyr Thr Glu Val Asp Ile Gly  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Glu Leu Leu Met Leu Lys Leu Lys Trp Lys Ser Asp Ser Tyr Phe Ser  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Trp Ser Asp Trp Trp Ser Ser Pro Gly Phe Ala Ile Gln Lys Ile Arg  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Val Lys Ala Gly Glu Thr Gln Lys Lys Val Ile Phe Cys Ser Arg Glu  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Lys Val Ser His Leu Gln Lys Gly Lys Ala Pro Ala Val Phe Val Lys  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Cys His Asp Lys Ser Leu Asn Lys Lys Ser Gly  
               
               
                 465                 470                 475  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 15  
               
               
                 &lt;211&gt; LENGTH: 1466  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (115)...(1305)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding apolipoprotein  
               
               
                       A-IV (APOA4)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 15  
               
               
                   
               
               
                 agttcccact gcagcgcagg tgagctctcc tgaggacctc tctgtcagct cccctgattg     60  
               
               
                   
               
               
                 tagggaggca tccagtgtgg caagaaactc ctccagccca gcaagcagct cagg atg      117  
               
               
                                                                             Met  
               
               
                                                                              1  
               
               
                   
               
               
                 ttc ctg aag gcc gtg gtc ctg acc ctg gcc ctg gtg gct gtc gcc gga      165  
               
               
                 Phe Leu Lys Ala Val Val Leu Thr Leu Ala Leu Val Ala Val Ala Gly  
               
               
                              5                   10                  15  
               
               
                   
               
               
                 gcc agg gct gag gtc agt gct gac cag gtg gcc aca gtg atg tgg gac      213  
               
               
                 Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp Asp  
               
               
                          20                  25                  30  
               
               
                   
               
               
                 tac ttc agc cag ctg agc aac aat gcc aag gag gcc gtg gaa cat ctc      261  
               
               
                 Tyr Phe Ser Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu His Leu  
               
               
                      35                  40                  45  
               
               
                   
               
               
                 cag aaa tct gaa ctc acc cag caa ctc aat gcc ctc ttc cag gac aaa      309  
               
               
                 Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp Lys  
               
               
                  50                  55                  60                  65  
               
               
                   
               
               
                 ctt gga gaa gtg aac act tac gca ggt gac ctg cag aag aag ctg gtg      357  
               
               
                 Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu Val  
               
               
                                  70                  75                  80  
               
               
                   
               
               
                 ccc ttt gcc acc gag ctg cat gaa cgc ctg gcc aag gac tcg gag aaa      405  
               
               
                 Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Glu Lys  
               
               
                              85                  90                  95  
               
               
                   
               
               
                 ctg aag gag gag att ggg aag gag ctg gag gag ctg agg gcc cgg ctg      453  
               
               
                 Leu Lys Glu Glu Ile Gly Lys Glu Leu Glu Glu Leu Arg Ala Arg Leu  
               
               
                         100                 105                 110  
               
               
                   
               
               
                 ctg ccc cat gcc aat gag gtg agc cag aag atc ggg gac aac ctg cga      501  
               
               
                 Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Asp Asn Leu Arg  
               
               
                     115                 120                 125  
               
               
                   
               
               
                 gag ctt cag cag cgc ctg gag ccc tac gcg gac cag ctg cgc acc cag      549  
               
               
                 Glu Leu Gln Gln Arg Leu Glu Pro Tyr Ala Asp Gln Leu Arg Thr Gln  
               
               
                 130                 135                 140                 145  
               
               
                   
               
               
                 gtc aac acg cag gcc gag cag ctg cgg cgc cag ctg acc ccc tac gca      597  
               
               
                 Val Asn Thr Gln Ala Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr Ala  
               
               
                                 150                 155                 160  
               
               
                   
               
               
                 cag cgc atg gag aga gtg ctg cgg gag aac gcc gac agc ctg cag gcc      645  
               
               
                 Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln Ala  
               
               
                             165                 170                 175  
               
               
                   
               
               
                 tcg ctg agg ccc cac gcc gac gag ctc aag gcc aag atc gac cag aac      693  
               
               
                 Ser Leu Arg Pro His Ala Asp Glu Leu Lys Ala Lys Ile Asp Gln Asn  
               
               
                         180                 185                 190  
               
               
                   
               
               
                 gtg gag gag ctc aag gga cgc ctt acg ccc tac gct gac gaa ttc aaa      741  
               
               
                 Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe Lys  
               
               
                     195                 200                 205  
               
               
                   
               
               
                 gtc aag att gac cag acc gtg gag gag ctg cgc cgc agc ctg gct ccc      789  
               
               
                 Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala Pro  
               
               
                 210                 215                 220                 225  
               
               
                   
               
               
                 tat gct cag gac acg cag gag aag ctc aac cac cag ctt gag ggc ctg      837  
               
               
                 Tyr Ala Gln Asp Thr Gln Glu Lys Leu Asn His Gln Leu Glu Gly Leu  
               
               
                                 230                 235                 240  
               
               
                   
               
               
                 acc ttc cag atg aag aag aac gcc gag gag ctc aag gcc agg atc tcg      885  
               
               
                 Thr Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile Ser  
               
               
                             245                 250                 255  
               
               
                   
               
               
                 gcc agt gcc gag gag ctg cgg cag agg ctg gcg ccc ttg gcc gag gac      933  
               
               
                 Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu Asp  
               
               
                         260                 265                 270  
               
               
                   
               
               
                 gtg cgt ggc aac ctg agg ggc aac acc gag ggg ctg cag aag tca ctg      981  
               
               
                 Val Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser Leu  
               
               
                     275                 280                 285  
               
               
                   
               
               
                 gca gag ctg ggt ggg cac ctg gac cag cag gtg gag gag ttc cga cgc     1029  
               
               
                 Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe Arg Arg  
               
               
                 290                 295                 300                 305  
               
               
                   
               
               
                 cgg gtg gag ccc tac ggg gaa aac ttc aac aaa gcc ctg gtg cag cag     1077  
               
               
                 Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln Gln  
               
               
                                 310                 315                 320  
               
               
                   
               
               
                 atg gaa cag ctc agg acg aaa ctg ggc ccc cat gcg ggg gac gtg gaa     1125  
               
               
                 Met Glu Gln Leu Arg Thr Lys Leu Gly Pro His Ala Gly Asp Val Glu  
               
               
                             325                 330                 335  
               
               
                   
               
               
                 ggc cac ttg agc ttc ctg gag aag gac ctg agg gac aag gtc aac tcc     1173  
               
               
                 Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn Ser  
               
               
                         340                 345                 350  
               
               
                   
               
               
                 ttc ttc agc acc ttc aag gag aaa gag agc cag gac aag act ctc tcc     1221  
               
               
                 Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Lys Thr Leu Ser  
               
               
                     355                 360                 365  
               
               
                   
               
               
                 ctc cct gag ctg gag caa cag cag gaa cag cat cag gag cag cag cag     1269  
               
               
                 Leu Pro Glu Leu Glu Gln Gln Gln Glu Gln His Gln Glu Gln Gln Gln  
               
               
                 370                 375                 380                 385  
               
               
                   
               
               
                 gag cag gtg cag atg ctg gcc cct ttg gag agc tga gctgcccctg          1315  
               
               
                 Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser  *  
               
               
                                 390                 395  
               
               
                   
               
               
                 gtgcactggc cccaccctcg tggacacctg ccctgccctg ccacctgtct gtctgtccca   1375  
               
               
                   
               
               
                 aagaagttct ggtatgaact tgaggacaca tgtccagtgg gaggtgagac cacctctcaa   1435  
               
               
                   
               
               
                 tattcaataa agctgctgag aatctagcct c                                  1466  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 16  
               
               
                 &lt;211&gt; LENGTH: 396  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 16  
               
               
                   
               
               
                 Met Phe Leu Lys Ala Val Val Leu Thr Leu Ala Leu Val Ala Val Ala  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Asp Tyr Phe Ser Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu His  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Glu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Lys Leu Lys Glu Glu Ile Gly Lys Glu Leu Glu Glu Leu Arg Ala Arg  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Asp Asn Leu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Ala Asp Gln Leu Arg Thr  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Gln Val Asn Thr Gln Ala Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Ser Leu Arg Pro His Ala Asp Glu Leu Lys Ala Lys Ile Asp Gln  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Asn Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Pro Tyr Ala Gln Asp Thr Gln Glu Lys Leu Asn His Gln Leu Glu Gly  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Leu Thr Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Asp Val Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe Arg  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Arg Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gln Met Glu Gln Leu Arg Thr Lys Leu Gly Pro His Ala Gly Asp Val  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Lys Thr Leu  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Ser Leu Pro Glu Leu Glu Gln Gln Gln Glu Gln His Gln Glu Gln Gln  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser  
               
               
                 385                 390                 395  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 17  
               
               
                 &lt;211&gt; LENGTH: 1156  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (61)...(1014)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide Sequence encoding apolipoprotein E  
               
               
                       (APOE)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 17  
               
               
                   
               
               
                 cgcagcggag gtgaaggacg tccttcccca ggagccgact ggccaatcac aggcaggaag     60  
               
               
                   
               
               
                 atg aag gtt ctg tgg gct gcg ttg ctg gtc aca ttc ctg gca gga tgc      108  
               
               
                 Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys  
               
               
                  1               5                   10                  15  
               
               
                   
               
               
                 cag gcc aag gtg gag caa gcg gtg gag aca gag ccg gag ccc gag ctg      156  
               
               
                 Gln Ala Lys Val Glu Gln Ala Val Glu Thr Glu Pro Glu Pro Glu Leu  
               
               
                              20                  25                  30  
               
               
                   
               
               
                 cgc cag cag acc gag tgg cag agc ggc cag cgc tgg gaa ctg gca ctg      204  
               
               
                 Arg Gln Gln Thr Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu  
               
               
                          35                  40                  45  
               
               
                   
               
               
                 ggt cgc ttt tgg gat tac ctg cgc tgg gtg cag aca ctg tct gag cag      252  
               
               
                 Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln  
               
               
                      50                  55                  60  
               
               
                   
               
               
                 gtg cag gag gag ctg ctc agc tcc cag gtc acc cag gaa ctg agg gcg      300  
               
               
                 Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Arg Ala  
               
               
                  65                  70                  75                  80  
               
               
                   
               
               
                 ctg atg gac gag acc atg aag gag ttg aag gcc tac aaa tcg gaa ctg      348  
               
               
                 Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu  
               
               
                                  85                  90                  95  
               
               
                   
               
               
                 gag gaa caa ctg acc ccg gtg gcg gag gag acg cgg gca cgg ctg tcc      396  
               
               
                 Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 aag gag ctg cag gcg gcg cag gcc cgg ctg ggc gcg gac atg gag gac      444  
               
               
                 Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 gtg tgc ggc cgc ctg gtg cag tac cgc ggc gag gtg cag gcc atg ctc      492  
               
               
                 Val Cys Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 ggc cag agc acc gag gag ctg cgg gtg cgc ctc gcc tcc cac ctg cgc      540  
               
               
                 Gly Gln Ser Thr Glu Glu Leu Arg Val Arg Leu Ala Ser His Leu Arg  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 aag ctg cgt aag cgg ctc ctc cgc gat gcc gat gac ctg cag aag cgc      588  
               
               
                 Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 ctg gca gtg tac cag gcc ggg gcc cgc gag ggc gcc gag cgc ggc ctc      636  
               
               
                 Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 agc gcc atc cgc gag cgc ctg ggg ccc ctg gtg gaa cag ggc cgc gtg      684  
               
               
                 Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 cgg gcc gcc act gtg ggc tcc ctg gcc ggc cag ccg cta cag gag cgg      732  
               
               
                 Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 gcc cag gcc tgg ggc gag cgg ctg cgc gcg cgg atg gag gag atg ggc      780  
               
               
                 Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 agc cgg acc cgc gac cgc ctg gac gag gtg aag gag cag gtg gcg gag      828  
               
               
                 Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 gtg cgc gcc aag ctg gag gag cag gcc cag cag ata cgc ctg cag gcc      876  
               
               
                 Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 gag gcc ttc cag gcc cgc ctc aag agc tgg ttc gag ccc ctg gtg gaa      924  
               
               
                 Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 gac atg cag cgc cag tgg gcc ggg ctg gtg gag aag gtg cag gct gcc      972  
               
               
                 Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 gtg ggc acc agc gcc gcc cct gtg ccc agc gac aat cac tga             1014  
               
               
                 Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His  *  
               
               
                 305                 310                 315  
               
               
                   
               
               
                 acgccgaagc ctgcagccat gcgaccccac gccaccccgt gcctcctgcc tccgcgcagc   1074  
               
               
                   
               
               
                 ctgcagcggg agaccctgtc cccgccccag ccgtcctcct ggggtggacc ctagtttaat   1134  
               
               
                   
               
               
                 aaagattcac caagtttcac gc                                            1156  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 18  
               
               
                 &lt;211&gt; LENGTH: 317  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 18  
               
               
                   
               
               
                 Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gln Ala Lys Val Glu Gln Ala Val Glu Thr Glu Pro Glu Pro Glu Leu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Arg Gln Gln Thr Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Arg Ala  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Val Cys Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Gly Gln Ser Thr Glu Glu Leu Arg Val Arg Leu Ala Ser His Leu Arg  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Leu  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His  
               
               
                 305                 310                 315  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 19  
               
               
                 &lt;211&gt; LENGTH: 1603  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (58)...(1557)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding hepatic lipase  
               
               
                       (LIPC)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 19  
               
               
                   
               
               
                 ggtctctttg gcttcagaaa ttaccaagaa agcctggacc ccgggtgaaa cggagaa atg    60  
               
               
                                                                                Met  
               
               
                                                                                 1  
               
               
                   
               
               
                 gac aca agt ccc ctg tgt ttc tcc att ctg ttg gtt tta tgc atc ttt      108  
               
               
                 Asp Thr Ser Pro Leu Cys Phe Ser Ile Leu Leu Val Leu Cys Ile Phe  
               
               
                              5                   10                  15  
               
               
                   
               
               
                 atc caa tca agt gcc ctt gga caa agc ctg aaa cca gag cca ttt gga      156  
               
               
                 Ile Gln Ser Ser Ala Leu Gly Gln Ser Leu Lys Pro Glu Pro Phe Gly  
               
               
                          20                  25                  30  
               
               
                   
               
               
                 aga aga gct caa gct gtt gaa aca aac aaa acg ctg cat gag atg aag      204  
               
               
                 Arg Arg Ala Gln Ala Val Glu Thr Asn Lys Thr Leu His Glu Met Lys  
               
               
                      35                  40                  45  
               
               
                   
               
               
                 acc aga ttc ctg ctc ttt gga gaa acc aat cag ggc tgt cag att cga      252  
               
               
                 Thr Arg Phe Leu Leu Phe Gly Glu Thr Asn Gln Gly Cys Gln Ile Arg  
               
               
                  50                  55                  60                  65  
               
               
                   
               
               
                 atc aat cat ccg gac acg tta cag gag tgc ggc ttc aac tcc tcc ctg      300  
               
               
                 Ile Asn His Pro Asp Thr Leu Gln Glu Cys Gly Phe Asn Ser Ser Leu  
               
               
                                  70                  75                  80  
               
               
                   
               
               
                 cct ctg gtg atg ata atc cac ggg tgg tcg gtg gac ggc gtg cta gaa      348  
               
               
                 Pro Leu Val Met Ile Ile His Gly Trp Ser Val Asp Gly Val Leu Glu  
               
               
                              85                  90                  95  
               
               
                   
               
               
                 aac tgg atc tgg cag atg gtg gcc gcg ctg aag tct cag ccg gcc cag      396  
               
               
                 Asn Trp Ile Trp Gln Met Val Ala Ala Leu Lys Ser Gln Pro Ala Gln  
               
               
                         100                 105                 110  
               
               
                   
               
               
                 cca gtg aac gtg ggg ctg gtg gac tgg atc acc ctg gcc cac gac cac      444  
               
               
                 Pro Val Asn Val Gly Leu Val Asp Trp Ile Thr Leu Ala His Asp His  
               
               
                     115                 120                 125  
               
               
                   
               
               
                 tac acc atc gcc gtc cgc aac acc cgc ctt gtg ggc aag gag gtc gcg      492  
               
               
                 Tyr Thr Ile Ala Val Arg Asn Thr Arg Leu Val Gly Lys Glu Val Ala  
               
               
                 130                 135                 140                 145  
               
               
                   
               
               
                 gct ctt ctc cgg tgg ctg gag gaa tct gtt caa ctc tct cga agc cat      540  
               
               
                 Ala Leu Leu Arg Trp Leu Glu Glu Ser Val Gln Leu Ser Arg Ser His  
               
               
                                 150                 155                 160  
               
               
                   
               
               
                 gtt cac cta att ggg tac agc ctg ggt gca cac gtg tca gga ttt gcc      588  
               
               
                 Val His Leu Ile Gly Tyr Ser Leu Gly Ala His Val Ser Gly Phe Ala  
               
               
                             165                 170                 175  
               
               
                   
               
               
                 ggc agt tcc atc ggt gga acg cac aag att ggg aga atc aca ggg ctg      636  
               
               
                 Gly Ser Ser Ile Gly Gly Thr His Lys Ile Gly Arg Ile Thr Gly Leu  
               
               
                         180                 185                 190  
               
               
                   
               
               
                 gat gcc gcg gga cct ttg ttt gag gga agt gcc ccc agc aat cgt ctt      684  
               
               
                 Asp Ala Ala Gly Pro Leu Phe Glu Gly Ser Ala Pro Ser Asn Arg Leu  
               
               
                     195                 200                 205  
               
               
                   
               
               
                 tct cca gat gat gcc aat ttt gtg gat gcc att cat acc ttt acg cgg      732  
               
               
                 Ser Pro Asp Asp Ala Asn Phe Val Asp Ala Ile His Thr Phe Thr Arg  
               
               
                 210                 215                 220                 225  
               
               
                   
               
               
                 gag cac atg ggc ctg agc gtg ggc atc aaa cag ccc ata gga cac tat      780  
               
               
                 Glu His Met Gly Leu Ser Val Gly Ile Lys Gln Pro Ile Gly His Tyr  
               
               
                                 230                 235                 240  
               
               
                   
               
               
                 gac ttc tat ccc aac ggg ggc tcc ttc cag cct ggc tgc cac ttc cta      828  
               
               
                 Asp Phe Tyr Pro Asn Gly Gly Ser Phe Gln Pro Gly Cys His Phe Leu  
               
               
                             245                 250                 255  
               
               
                   
               
               
                 gag ctc tac aga cat att gcc cag cac ggc ttc aat gcc atc acc cag      876  
               
               
                 Glu Leu Tyr Arg His Ile Ala Gln His Gly Phe Asn Ala Ile Thr Gln  
               
               
                         260                 265                 270  
               
               
                   
               
               
                 acc ata aaa tgc tcc cac gag cga tcg gtg cac ctt ttc atc gac tcc      924  
               
               
                 Thr Ile Lys Cys Ser His Glu Arg Ser Val His Leu Phe Ile Asp Ser  
               
               
                     275                 280                 285  
               
               
                   
               
               
                 ttg ctg cac gcc ggc acg cag agc atg gcc tac ccg tgt ggt gac atg      972  
               
               
                 Leu Leu His Ala Gly Thr Gln Ser Met Ala Tyr Pro Cys Gly Asp Met  
               
               
                 290                 295                 300                 305  
               
               
                   
               
               
                 aac agc ttc agc cag ggc ctg tgc ctg agc tgc aag aag ggc cgc tgc     1020  
               
               
                 Asn Ser Phe Ser Gln Gly Leu Cys Leu Ser Cys Lys Lys Gly Arg Cys  
               
               
                                 310                 315                 320  
               
               
                   
               
               
                 aac acg ctg ggc tac cac gtc cgc cag gag ccg cgg agc aag agc aag     1068  
               
               
                 Asn Thr Leu Gly Tyr His Val Arg Gln Glu Pro Arg Ser Lys Ser Lys  
               
               
                             325                 330                 335  
               
               
                   
               
               
                 agg ctc ttc ctc gta acg cga gcc cag tcc ccc ttc aaa gtt tat cat     1116  
               
               
                 Arg Leu Phe Leu Val Thr Arg Ala Gln Ser Pro Phe Lys Val Tyr His  
               
               
                         340                 345                 350  
               
               
                   
               
               
                 tac cag tta aag atc cag ttc atc aac caa act gag acg cca ata caa     1164  
               
               
                 Tyr Gln Leu Lys Ile Gln Phe Ile Asn Gln Thr Glu Thr Pro Ile Gln  
               
               
                     355                 360                 365  
               
               
                   
               
               
                 aca act ttt acc atg tca cta ctc gga aca aaa gag aaa atg cag aaa     1212  
               
               
                 Thr Thr Phe Thr Met Ser Leu Leu Gly Thr Lys Glu Lys Met Gln Lys  
               
               
                 370                 375                 380                 385  
               
               
                   
               
               
                 att ccc atc act ctg ggc aaa gga att gct agt aat aaa acg tat tcc     1260  
               
               
                 Ile Pro Ile Thr Leu Gly Lys Gly Ile Ala Ser Asn Lys Thr Tyr Ser  
               
               
                                 390                 395                 400  
               
               
                   
               
               
                 ttt ctt atc acg ctg gat gtg gat atc ggc gag ctg atc atg atc aag     1308  
               
               
                 Phe Leu Ile Thr Leu Asp Val Asp Ile Gly Glu Leu Ile Met Ile Lys  
               
               
                             405                 410                 415  
               
               
                   
               
               
                 ttc aag tgg gaa aac agt gca gtg tgg gcc aat gtc tgg gac acg gtc     1356  
               
               
                 Phe Lys Trp Glu Asn Ser Ala Val Trp Ala Asn Val Trp Asp Thr Val  
               
               
                         420                 425                 430  
               
               
                   
               
               
                 cag acc atc atc cca tgg agc aca ggg ccg cgc cac tca ggc ctc gtt     1404  
               
               
                 Gln Thr Ile Ile Pro Trp Ser Thr Gly Pro Arg His Ser Gly Leu Val  
               
               
                     435                 440                 445  
               
               
                   
               
               
                 ctg aag acg atc aga gtc aaa gca gga gaa acc cag caa aga atg aca     1452  
               
               
                 Leu Lys Thr Ile Arg Val Lys Ala Gly Glu Thr Gln Gln Arg Met Thr  
               
               
                 450                 455                 460                 465  
               
               
                   
               
               
                 ttt tgt tca gaa aac aca gat gac cta cta ctt cgc cca acc cag gaa     1500  
               
               
                 Phe Cys Ser Glu Asn Thr Asp Asp Leu Leu Leu Arg Pro Thr Gln Glu  
               
               
                                 470                 475                 480  
               
               
                   
               
               
                 aaa atc ttc gtg aaa tgt gaa ata aag tct aaa aca tca aag cga aag     1548  
               
               
                 Lys Ile Phe Val Lys Cys Glu Ile Lys Ser Lys Thr Ser Lys Arg Lys  
               
               
                             485                 490                 495  
               
               
                   
               
               
                 atc aga tga gatttaatga agacccagtg taaagaataa atgaatctta             1597  
               
               
                 Ile Arg  *  
               
               
                   
               
               
                 ctcctt                                                              1603  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 20  
               
               
                 &lt;211&gt; LENGTH: 499  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 20  
               
               
                   
               
               
                 Met Asp Thr Ser Pro Leu Cys Phe Ser Ile Leu Leu Val Leu Cys Ile  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Phe Ile Gln Ser Ser Ala Leu Gly Gln Ser Leu Lys Pro Glu Pro Phe  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Gly Arg Arg Ala Gln Ala Val Glu Thr Asn Lys Thr Leu His Glu Met  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Lys Thr Arg Phe Leu Leu Phe Gly Glu Thr Asn Gln Gly Cys Gln Ile  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Arg Ile Asn His Pro Asp Thr Leu Gln Glu Cys Gly Phe Asn Ser Ser  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Leu Pro Leu Val Met Ile Ile His Gly Trp Ser Val Asp Gly Val Leu  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Glu Asn Trp Ile Trp Gln Met Val Ala Ala Leu Lys Ser Gln Pro Ala  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Gln Pro Val Asn Val Gly Leu Val Asp Trp Ile Thr Leu Ala His Asp  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 His Tyr Thr Ile Ala Val Arg Asn Thr Arg Leu Val Gly Lys Glu Val  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Ala Leu Leu Arg Trp Leu Glu Glu Ser Val Gln Leu Ser Arg Ser  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 His Val His Leu Ile Gly Tyr Ser Leu Gly Ala His Val Ser Gly Phe  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Gly Ser Ser Ile Gly Gly Thr His Lys Ile Gly Arg Ile Thr Gly  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Leu Asp Ala Ala Gly Pro Leu Phe Glu Gly Ser Ala Pro Ser Asn Arg  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu Ser Pro Asp Asp Ala Asn Phe Val Asp Ala Ile His Thr Phe Thr  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Arg Glu His Met Gly Leu Ser Val Gly Ile Lys Gln Pro Ile Gly His  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Tyr Asp Phe Tyr Pro Asn Gly Gly Ser Phe Gln Pro Gly Cys His Phe  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Leu Glu Leu Tyr Arg His Ile Ala Gln His Gly Phe Asn Ala Ile Thr  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Gln Thr Ile Lys Cys Ser His Glu Arg Ser Val His Leu Phe Ile Asp  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Ser Leu Leu His Ala Gly Thr Gln Ser Met Ala Tyr Pro Cys Gly Asp  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Met Asn Ser Phe Ser Gln Gly Leu Cys Leu Ser Cys Lys Lys Gly Arg  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Cys Asn Thr Leu Gly Tyr His Val Arg Gln Glu Pro Arg Ser Lys Ser  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Lys Arg Leu Phe Leu Val Thr Arg Ala Gln Ser Pro Phe Lys Val Tyr  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 His Tyr Gln Leu Lys Ile Gln Phe Ile Asn Gln Thr Glu Thr Pro Ile  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Gln Thr Thr Phe Thr Met Ser Leu Leu Gly Thr Lys Glu Lys Met Gln  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Lys Ile Pro Ile Thr Leu Gly Lys Gly Ile Ala Ser Asn Lys Thr Tyr  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Ser Phe Leu Ile Thr Leu Asp Val Asp Ile Gly Glu Leu Ile Met Ile  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Lys Phe Lys Trp Glu Asn Ser Ala Val Trp Ala Asn Val Trp Asp Thr  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Val Gln Thr Ile Ile Pro Trp Ser Thr Gly Pro Arg His Ser Gly Leu  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Val Leu Lys Thr Ile Arg Val Lys Ala Gly Glu Thr Gln Gln Arg Met  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Thr Phe Cys Ser Glu Asn Thr Asp Asp Leu Leu Leu Arg Pro Thr Gln  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Glu Lys Ile Phe Val Lys Cys Glu Ile Lys Ser Lys Thr Ser Lys Arg  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Lys Ile Arg  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 21  
               
               
                 &lt;211&gt; LENGTH: 1346  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (10)...(1077)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding paraoxonase  
               
               
                       1 (PON1)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 21  
               
               
                   
               
               
                 cccccgacc atg gcg aag ctg att gcg ctc acc ctc ttg ggg atg gga ctg     51  
               
               
                           Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu  
               
               
                            1               5                   10  
               
               
                   
               
               
                 gca ctc ttc agg aac cac cag tct tct tac caa aca cga ctt aat gct       99  
               
               
                 Ala Leu Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala  
               
               
                  15                  20                  25                  30  
               
               
                   
               
               
                 ctc cga gag gta caa ccc gta gaa ctt cct aac tgt aat tta gtt aaa      147  
               
               
                 Leu Arg Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys  
               
               
                                  35                  40                  45  
               
               
                   
               
               
                 gga atc gaa act ggc tct gaa gac atg gag ata ctg cct aat gga ctg      195  
               
               
                 Gly Ile Glu Thr Gly Ser Glu Asp Met Glu Ile Leu Pro Asn Gly Leu  
               
               
                              50                  55                  60  
               
               
                   
               
               
                 gct ttc att agc tct gga tta aag tat cct gga ata aag agc ttc aac      243  
               
               
                 Ala Phe Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn  
               
               
                          65                  70                  75  
               
               
                   
               
               
                 ccc aac agt cct gga aaa ata ctt ctg atg gac ctg aat gaa gaa gat      291  
               
               
                 Pro Asn Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp  
               
               
                      80                  85                  90  
               
               
                   
               
               
                 cca aca gtg ttg gaa ttg ggg atc act gga agt aaa ttt gat gta tct      339  
               
               
                 Pro Thr Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser  
               
               
                  95                 100                 105                 110  
               
               
                   
               
               
                 tca ttt aac cct cat ggg att agc aca ttc aca gat gaa gat aat gcc      387  
               
               
                 Ser Phe Asn Pro His Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala  
               
               
                                 115                 120                 125  
               
               
                   
               
               
                 atg tac ctc ctg gtg gtg aac cat cca gat gcc aag tcc aca gtg gag      435  
               
               
                 Met Tyr Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu  
               
               
                             130                 135                 140  
               
               
                   
               
               
                 ttg ttt aaa ttt caa gaa gaa gaa aaa tcg ctt ttg cat cta aaa acc      483  
               
               
                 Leu Phe Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr  
               
               
                         145                 150                 155  
               
               
                   
               
               
                 atc aga cat aaa ctt ctg cct aat ttg aat gat att gtt gct gtg gga      531  
               
               
                 Ile Arg His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly  
               
               
                     160                 165                 170  
               
               
                   
               
               
                 cct gag cac ttt tat ggc aca aat gat cac tat ttt ctt gac ccc tac      579  
               
               
                 Pro Glu His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr  
               
               
                 175                 180                 185                 190  
               
               
                   
               
               
                 tta caa tcc tgg gag atg tat ttg ggt tta gcg tgg tcg tat gtt gtc      627  
               
               
                 Leu Gln Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val  
               
               
                                 195                 200                 205  
               
               
                   
               
               
                 tac tat agt cca agt gaa gtt cga gtg gtg gca gaa gga ttt gat ttt      675  
               
               
                 Tyr Tyr Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe  
               
               
                             210                 215                 220  
               
               
                   
               
               
                 gct aat gga atc aac att tca ccc gat ggc aag tat gtc tat ata gct      723  
               
               
                 Ala Asn Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala  
               
               
                         225                 230                 235  
               
               
                   
               
               
                 gag ttg ctg gct cat aag att cat gtg tat gaa aag cat gct aat tgg      771  
               
               
                 Glu Leu Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp  
               
               
                     240                 245                 250  
               
               
                   
               
               
                 act tta act cca ttg aag tcc ctt gac ttt aat acc ctc gtg gat aac      819  
               
               
                 Thr Leu Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn  
               
               
                 255                 260                 265                 270  
               
               
                   
               
               
                 ata tct gtg gat cct gag aca gga gac ctt tgg gtt gga tgc cat ccc      867  
               
               
                 Ile Ser Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro  
               
               
                                 275                 280                 285  
               
               
                   
               
               
                 aat ggc atg aaa atc ttc ttc tat gac tca gag aat cct cct gca tca      915  
               
               
                 Asn Gly Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser  
               
               
                             290                 295                 300  
               
               
                   
               
               
                 gag gtg ctt cga atc cag aac att cta aca gaa gaa cct aaa gtg aca      963  
               
               
                 Glu Val Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr  
               
               
                         305                 310                 315  
               
               
                   
               
               
                 cag gtt tat gca gaa aat ggc aca gtg ttg caa ggc agt aca gtt gcc     1011  
               
               
                 Gln Val Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala  
               
               
                     320                 325                 330  
               
               
                   
               
               
                 tct gtg tac aaa ggg aaa ctg ctg att ggc aca gtg ttt cac aaa gct     1059  
               
               
                 Ser Val Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala  
               
               
                 335                 340                 345                 350  
               
               
                   
               
               
                 ctt tac tgt gag ctc taa cagaccgatt tgcacccatg ccatagaaac            1107  
               
               
                 Leu Tyr Cys Glu Leu  *  
               
               
                                 355  
               
               
                   
               
               
                 tgaggccatt atttcaaccg cttgccatat tccgaggacc cagtgttctt agctgaacaa   1167  
               
               
                   
               
               
                 tgaatgctga ccctaaatgt ggacatcatg aagcatcaaa gcactgttta actgggagtg   1227  
               
               
                   
               
               
                 atatgatgtg tagggctttt ttttgagaat acactatcaa atcagtcttg gaatacttga   1287  
               
               
                   
               
               
                 aaacctcatt taccataaaa atccttctca ctaaaatgga taaatcagtt aaaaaaaaa    1346  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 22  
               
               
                 &lt;211&gt; LENGTH: 355  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 22  
               
               
                   
               
               
                 Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Glu Thr Gly Ser Glu Asp Met Glu Ile Leu Pro Asn Gly Leu Ala Phe  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Ser Phe  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Asn Pro His Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu Leu Phe  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Gln  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe Ala Asn  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala Ser Val  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Cys Glu Leu  
               
               
                         355  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 23  
               
               
                 &lt;211&gt; LENGTH: 1570  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (1)...(1097)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding paraoxonase  
               
               
                       2 (PON2)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 23  
               
               
                   
               
               
                 cgg agc gag gca gcg cgc ccg gct ccc gcg cca tgg ggc ggc tgg tgg       48  
               
               
                 Arg Ser Glu Ala Ala Arg Pro Ala Pro Ala Pro Trp Gly Gly Trp Trp  
               
               
                  1               5                   10                  15  
               
               
                   
               
               
                 ctg tgg gct tgc tgg gga tcg cgc tgg cgc tcc tgg gcg aga ggc ttc       96  
               
               
                 Leu Trp Ala Cys Trp Gly Ser Arg Trp Arg Ser Trp Ala Arg Gly Phe  
               
               
                              20                  25                  30  
               
               
                   
               
               
                 tgg cac tca gaa atc gac tta aag cct cca gag aag tag aat ctg tag      144  
               
               
                 Trp His Ser Glu Ile Asp Leu Lys Pro Pro Glu Lys  *  Asn Leu  *  
               
               
                          35                  40                      45  
               
               
                   
               
               
                 acc ttc cac act gcc acc tga tta aag gaa ttg aag ctg gct ctg aag      192  
               
               
                 Thr Phe His Thr Ala Thr  *  Leu Lys Glu Leu Lys Leu Ala Leu Lys  
               
               
                              50                      55                  60  
               
               
                   
               
               
                 ata ttg aca tac ttc cca atg gtc tgg ctt ttt tta gtg tgg gtc taa      240  
               
               
                 Ile Leu Thr Tyr Phe Pro Met Val Trp Leu Phe Leu Val Trp Val  *  
               
               
                              65                  70                  75  
               
               
                   
               
               
                 aat tcc cag gac tcc aca gct ttg cac cag ata agc ctg gag gaa tac      288  
               
               
                 Asn Ser Gln Asp Ser Thr Ala Leu His Gln Ile Ser Leu Glu Glu Tyr  
               
               
                              80                  85                  90  
               
               
                   
               
               
                 taa tga tgg atc taa aag aag aaa aac caa ggg cac ggg aat taa gaa      336  
               
               
                  *   *  Trp Ile  *  Lys Lys Lys Asn Gln Gly His Gly Asn  *  Glu  
               
               
                                      95                 100  
               
               
                   
               
               
                 tca gtc gtg ggt ttg att tgg cct cat tca atc cac atg gca tca gca      384  
               
               
                 Ser Val Val Gly Leu Ile Trp Pro His Ser Ile His Met Ala Ser Ala  
               
               
                 105                 110                 115                 120  
               
               
                   
               
               
                 ctt tca tag aca acg atg aca cag ttt atc tct ttg ttg taa acc acc      432  
               
               
                 Leu Ser  *  Thr Thr Met Thr Gln Phe Ile Ser Leu Leu  *  Thr Thr  
               
               
                                     125                 130  
               
               
                   
               
               
                 cag aat tca aga ata cag tgg aaa ttt tta aat ttg aag aag cag aaa      480  
               
               
                 Gln Asn Ser Arg Ile Gln Trp Lys Phe Leu Asn Leu Lys Lys Gln Lys  
               
               
                 135                 140                 145                 150  
               
               
                   
               
               
                 att ctc tgt tgc atc tga aaa cag tca aac atg agc ttc ttc caa gtg      528  
               
               
                 Ile Leu Cys Cys Ile  *  Lys Gln Ser Asn Met Ser Phe Phe Gln Val  
               
               
                                 155                     160                 165  
               
               
                   
               
               
                 tga atg aca tca cag ctg ttg gac cgg cac att tct atg cca caa atg      576  
               
               
                  *  Met Thr Ser Gln Leu Leu Asp Arg His Ile Ser Met Pro Gln Met  
               
               
                                     170                 175                 180  
               
               
                   
               
               
                 acc act act tct ctg atc ctt tct taa agt att tag aaa cat act tga      624  
               
               
                 Thr Thr Thr Ser Leu Ile Leu Ser  *  Ser Ile  *  Lys His Thr  *  
               
               
                                 185                     190  
               
               
                   
               
               
                 act tac act ggg caa atg ttg ttt act aca gtc caa atg aag tta aag      672  
               
               
                 Thr Tyr Thr Gly Gln Met Leu Phe Thr Thr Val Gln Met Lys Leu Lys  
               
               
                     195                 200                 205  
               
               
                   
               
               
                 tgg tag cag aag gat ttg att cag caa atg gga tca ata ttt cac ctg      720  
               
               
                 Trp  *  Gln Lys Asp Leu Ile Gln Gln Met Gly Ser Ile Phe His Leu  
               
               
                 210                     215                 220  
               
               
                   
               
               
                 atg ata agt ata tct atg ttg ctg aca tat tgg ctc atg aaa ttc atg      768  
               
               
                 Met Ile Ser Ile Ser Met Leu Leu Thr Tyr Trp Leu Met Lys Phe Met  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 ttt tgg aaa aac aca cta ata tga att taa ctc agt tga agg tac ttg      816  
               
               
                 Phe Trp Lys Asn Thr Leu Ile  *  Ile  *  Leu Ser  *  Arg Tyr Leu  
               
               
                                 245                         250  
               
               
                   
               
               
                 agc tgg ata cac tgg tgg ata att tat cta ttg atc ctt cct cgg ggg      864  
               
               
                 Ser Trp Ile His Trp Trp Ile Ile Tyr Leu Leu Ile Leu Pro Arg Gly  
               
               
                     255                 260                 265  
               
               
                   
               
               
                 aca tct ggg tag gct gtc atc cta atg gcc aga agc tct tcg tgt atg      912  
               
               
                 Thr Ser Gly  *  Ala Val Ile Leu Met Ala Arg Ser Ser Ser Cys Met  
               
               
                 270                     275                 280  
               
               
                   
               
               
                 acc cga aca atc ctc cct cgt cag agg ttc tcc gca tcc aga aca ttc      960  
               
               
                 Thr Arg Thr Ile Leu Pro Arg Gln Arg Phe Ser Ala Ser Arg Thr Phe  
               
               
                 285                 290                 295                 300  
               
               
                   
               
               
                 tat ctg aga agc cta cag tga cta cag ttt atg cca aca atg ggt ctg     1008  
               
               
                 Tyr Leu Arg Ser Leu Gln  *  Leu Gln Phe Met Pro Thr Met Gly Leu  
               
               
                                 305                     310                 315  
               
               
                   
               
               
                 ttc tcc aag gaa gtt ctg tag cct cag tgt atg atg gga agc tgc tca     1056  
               
               
                 Phe Ser Lys Glu Val Leu  *  Pro Gln Cys Met Met Gly Ser Cys Ser  
               
               
                                 320                     325                 330  
               
               
                   
               
               
                 tag gca ctt tat acc aca gag cct tgt att gtg aac tct aa attgtacttt   1107  
               
               
                  *  Ala Leu Tyr Thr Thr Glu Pro Cys Ile Val Asn Ser  
               
               
                                     335                 340  
               
               
                   
               
               
                 tggcatgaaa gtgcgataac ttaacaatta attttctatg aattgctaat tctgagggaa   1167  
               
               
                   
               
               
                 tttaaccagc aacattgacc cagaaatgta tggcatgtgt agttaatttt attccagtaa   1227  
               
               
                   
               
               
                 ggaacggccc ttttagttct tagagcactt ttaacaaaaa aggaaaatga acaggttctt   1287  
               
               
                   
               
               
                 taaaatgcca agcaagggac agaaaagaaa gctgctttcg aataaagtga atacattttg   1347  
               
               
                   
               
               
                 cacaaagtaa gcctcacctt tgccttccaa ctgccagaac atggattcca ctgaaataga   1407  
               
               
                   
               
               
                 gtgaattata tttccttaaa atgtgagtga cctcacttct ggcactgtga ctactatggc   1467  
               
               
                   
               
               
                 tgtttagaac tactgataac gtattttgat gttttgtact tacatctttg tttaccatta   1527  
               
               
                   
               
               
                 aaaagttgga gttatattaa agactaacta aaatcccagt ttt                     1570  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 24  
               
               
                 &lt;211&gt; LENGTH: 342  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 24  
               
               
                   
               
               
                 Arg Ser Glu Ala Ala Arg Pro Ala Pro Ala Pro Trp Gly Gly Trp Trp  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Leu Trp Ala Cys Trp Gly Ser Arg Trp Arg Ser Trp Ala Arg Gly Phe  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Trp His Ser Glu Ile Asp Leu Lys Pro Pro Glu Lys Asn Leu Thr Phe  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 His Thr Ala Thr Leu Lys Glu Leu Lys Leu Ala Leu Lys Ile Leu Thr  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Tyr Phe Pro Met Val Trp Leu Phe Leu Val Trp Val Asn Ser Gln Asp  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ser Thr Ala Leu His Gln Ile Ser Leu Glu Glu Tyr Trp Ile Lys Lys  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Lys Asn Gln Gly His Gly Asn Glu Ser Val Val Gly Leu Ile Trp Pro  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 His Ser Ile His Met Ala Ser Ala Leu Ser Thr Thr Met Thr Gln Phe  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Ile Ser Leu Leu Thr Thr Gln Asn Ser Arg Ile Gln Trp Lys Phe Leu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Asn Leu Lys Lys Gln Lys Ile Leu Cys Cys Ile Lys Gln Ser Asn Met  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ser Phe Phe Gln Val Met Thr Ser Gln Leu Leu Asp Arg His Ile Ser  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Met Pro Gln Met Thr Thr Thr Ser Leu Ile Leu Ser Ser Ile Lys His  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Thr Thr Tyr Thr Gly Gln Met Leu Phe Thr Thr Val Gln Met Lys Leu  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Lys Trp Gln Lys Asp Leu Ile Gln Gln Met Gly Ser Ile Phe His Leu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Met Ile Ser Ile Ser Met Leu Leu Thr Tyr Trp Leu Met Lys Phe Met  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Phe Trp Lys Asn Thr Leu Ile Ile Leu Ser Arg Tyr Leu Ser Trp Ile  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 His Trp Trp Ile Ile Tyr Leu Leu Ile Leu Pro Arg Gly Thr Ser Gly  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Ala Val Ile Leu Met Ala Arg Ser Ser Ser Cys Met Thr Arg Thr Ile  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Leu Pro Arg Gln Arg Phe Ser Ala Ser Arg Thr Phe Tyr Leu Arg Ser  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Leu Gln Leu Gln Phe Met Pro Thr Met Gly Leu Phe Ser Lys Glu Val  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Leu Pro Gln Cys Met Met Gly Ser Cys Ser Ala Leu Tyr Thr Thr Glu  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Pro Cys Ile Val Asn Ser  
               
               
                             340  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 25  
               
               
                 &lt;211&gt; LENGTH: 533  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (47)...(346)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding apolipoprotein  
               
               
                       C-III(APOC3)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 25  
               
               
                   
               
               
                 tgctcagttc atccctagag gcagctgctc caggaacaga ggtgcc atg cag ccc        55  
               
               
                                                                    Met Gln Pro  
               
               
                                                                     1  
               
               
                   
               
               
                 cgg gta ctc ctt gtt gtt gcc ctc ctg gcg ctc ctg gcc tct gcc cga      103  
               
               
                 Arg Val Leu Leu Val Val Ala Leu Leu Ala Leu Leu Ala Ser Ala Arg  
               
               
                      5                   10                  15  
               
               
                   
               
               
                 gct tca gag gcc gag gat gcc tcc ctt ctc agc ttc atg cag ggt tac      151  
               
               
                 Ala Ser Glu Ala Glu Asp Ala Ser Leu Leu Ser Phe Met Gln Gly Tyr  
               
               
                  20                  25                  30                  35  
               
               
                   
               
               
                 atg aag cac gcc acc aag acc gcc aag gat gca ctg agc agc gtg cag      199  
               
               
                 Met Lys His Ala Thr Lys Thr Ala Lys Asp Ala Leu Ser Ser Val Gln  
               
               
                                  40                  45                  50  
               
               
                   
               
               
                 gag tcc cag gtg gcc cag cag gcc agg ggc tgg gtg acc gat ggc ttc      247  
               
               
                 Glu Ser Gln Val Ala Gln Gln Ala Arg Gly Trp Val Thr Asp Gly Phe  
               
               
                              55                  60                  65  
               
               
                   
               
               
                 agt tcc ctg aaa gac tac tgg agc acc gtt aag gac aag ttc tct gag      295  
               
               
                 Ser Ser Leu Lys Asp Tyr Trp Ser Thr Val Lys Asp Lys Phe Ser Glu  
               
               
                          70                  75                  80  
               
               
                   
               
               
                 ttc tgg gat ttg gac cct gag gtc aga cca act tca gcc gtg gct gcc      343  
               
               
                 Phe Trp Asp Leu Asp Pro Glu Val Arg Pro Thr Ser Ala Val Ala Ala  
               
               
                      85                  90                  95  
               
               
                   
               
               
                 tga gacctcaata ccccaagtcc acctgcctat ccatcctgcg agctccttgg           396  
               
               
                   
               
               
                 gtcctgcaat ctccagggct gcccctgtag gttgcttaaa agggacagta ttctcagtgc    456  
               
               
                   
               
               
                 tctcctaccc cacctcatgc ctggcccccc tccaggcatg ctggcctccc aataaagctg    516  
               
               
                   
               
               
                 gacaagaagc tgctatg                                                   533  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 26  
               
               
                 &lt;211&gt; LENGTH: 99  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 26  
               
               
                   
               
               
                 Met Gln Pro Arg Val Leu Leu Val Val Ala Leu Leu Ala Leu Leu Ala  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Ser Ala Arg Ala Ser Glu Ala Glu Asp Ala Ser Leu Leu Ser Phe Met  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Gln Gly Tyr Met Lys His Ala Thr Lys Thr Ala Lys Asp Ala Leu Ser  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ser Val Gln Glu Ser Gln Val Ala Gln Gln Ala Arg Gly Trp Val Thr  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Asp Gly Phe Ser Ser Leu Lys Asp Tyr Trp Ser Thr Val Lys Asp Lys  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Phe Ser Glu Phe Trp Asp Leu Asp Pro Glu Val Arg Pro Thr Ser Ala  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Val Ala Ala  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 27  
               
               
                 &lt;211&gt; LENGTH: 8925  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: misc_feature  
               
               
                 &lt;222&gt; LOCATION: 5081, 5082, 5083, 5084, 5085, 5086, 5087, 5088, 5089,  
               
               
                       5090, 5091, 5092, 5093, 5094, 5095, 5096, 5097, 5098, 5099, 5100,  
               
               
                       5101, 5102, 5103, 5104, 5105, 5106, 5107, 5108, 5109, 5110,  
               
               
                       5111, 5112, 5113, 5114, 5115, 5116, 5117, 5118, 5119  
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: misc_feature  
               
               
                 &lt;222&gt; LOCATION: 5120, 5121, 5122, 5123, 5124, 5125, 5126, 5127, 5128,  
               
               
                       5129, 5130, 5131, 5132, 5133, 5134, 5135, 5136, 5137, 5138, 5139,  
               
               
                       5140, 5141, 5142, 5143, 5144, 5145, 5146, 5147, 5148, 5149,  
               
               
                       5150, 5151, 5152, 5153, 5154, 5155, 5156, 5157, 5158  
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: misc_feature  
               
               
                 &lt;222&gt; LOCATION: 5159, 5160, 5161, 5162, 5163, 5164, 5165, 5166, 5167,  
               
               
                       5168, 5169, 5170, 5171, 5172, 5173, 5174, 5175, 5176, 5177, 5178,  
               
               
                       5179  
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (5020)...(6162)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide encoding ATP-binding cassette (ABC1)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 27  
               
               
                   
               
               
                 ctcagtgtca gctgctgctg gaagtggcct ggcctctatt tatcttcctg atcctgatct     60  
               
               
                   
               
               
                 ctgttcggct gagctaccca ccctatgaac aacatgaatg ccattttcca aataaagcca    120  
               
               
                   
               
               
                 tgccctctgc aggaacactt ccttgggttc aggggattat ctgtaatgcc aacaacccct    180  
               
               
                   
               
               
                 gtttccgtta cccgactcct ggggaggctc ccggagttgt tggaaacttt aacaaatcca    240  
               
               
                   
               
               
                 ttgtggctcg cctgttctca gatgctcgga ggcttctttt atacagccag aaagacacca    300  
               
               
                   
               
               
                 gcatgaagga catgcgcaaa gttctgagaa cattacagca gatcaagaaa tccagctcaa    360  
               
               
                   
               
               
                 acttgaagct tcaagatttc ctggtggaca atgaaacctt ctctgggttc ctgtatcaca    420  
               
               
                   
               
               
                 acctctctct cccaaagtct actgtggaca agatgctgag ggctgatgtc attctccaca    480  
               
               
                   
               
               
                 aggtattttt gcaaggctac cagttacatt tgacaagtct gtgcaatgga tcaaaatcag    540  
               
               
                   
               
               
                 aagagatgat tcaacttggt gaccaagaag tttctgagct ttgtggccta ccaagggaga    600  
               
               
                   
               
               
                 aactggctgc agcagagcga gtacttcgtt ccaacatgga catcctgaag ccaatcctga    660  
               
               
                   
               
               
                 gaacactaaa ctctacatct cccttcccga gcaaggagct ggctgaagcc acaaaaacat    720  
               
               
                   
               
               
                 tgctgcatag tcttgggact ctggcccagg agctgttcag catgagaagc tggagtgaca    780  
               
               
                   
               
               
                 tgcgacagga ggtgatgttt ctgaccaatg tgaacagctc cagctcctcc acccaaatct    840  
               
               
                   
               
               
                 accaggctgt gtctcgtatt gtctgcgggc atcccgaggg aggggggctg aagatcaagt    900  
               
               
                   
               
               
                 ctctcaactg gtatgaggac aacaactaca aagccctctt tggaggcaat ggcactgagg    960  
               
               
                   
               
               
                 aagatgctga aaccttctat gacaactcta caactcctta ctgcaatgat ttgatgaaga   1020  
               
               
                   
               
               
                 atttggagtc tagtcctctt tcccgcatta tctggaaagc tctgaagccg ctgctcgttg   1080  
               
               
                   
               
               
                 ggaagatcct gtatacacct gacactccag ccacaaggca ggtcatggct gaggtgaaca   1140  
               
               
                   
               
               
                 agaccttcca ggaactggct gtgttccatg atctggaagg catgtgggag gaactcagcc   1200  
               
               
                   
               
               
                 ccaagatctg gaccttcatg gagaacagcc aagaaatgga ccttgtccgg atgctgttgg   1260  
               
               
                   
               
               
                 acagcaggga caatgaccac ttttgggaac agcagttgga tggcttagat tggacagccc   1320  
               
               
                   
               
               
                 aagacatcgt ggcgtttttg gccaagcacc cagaggatgt ccagtccagt aatggttctg   1380  
               
               
                   
               
               
                 tgtacacctg gagagaagct ttcaacgaga ctaaccaggc aatccggacc atatctcgct   1440  
               
               
                   
               
               
                 tcatggagtg tgtcaacctg aacaagctag aacccatagc aacagaagtc tggctcatca   1500  
               
               
                   
               
               
                 acaagtccat ggagctgctg gatgagagga agttctgggc tggtattgtg ttcactggaa   1560  
               
               
                   
               
               
                 ttactccagg cagcattgag ctgccccatc atgtcaagta caagatccga atggacattg   1620  
               
               
                   
               
               
                 acaatgtgga gaggacaaat aaaatcaagg atgggtactg ggaccctggt cctcgagctg   1680  
               
               
                   
               
               
                 acccctttga ggacatgcgg tacgtctggg ggggcttcgc ctacttgcag gatgtggtgg   1740  
               
               
                   
               
               
                 agcaggcaat catcagggtg ctgacgggca ccgagaagaa aactggtgtc tatatgcaac   1800  
               
               
                   
               
               
                 agatgcccta tccctgttac gttgatgaca tctttctgcg ggtgatgagc cggtcaatgc   1860  
               
               
                   
               
               
                 ccctcttcat gacgctggcc tggatttact cagtggctgt gatcatcaag ggcatcgtgt   1920  
               
               
                   
               
               
                 atgagaagga ggcacggctg aaagagacca tgcggatcat gggcctggac aacagcatcc   1980  
               
               
                   
               
               
                 tctggtttag ctggttcatt agtagcctca ttcctcttct tgtgagcgct ggcctgctag   2040  
               
               
                   
               
               
                 tggtcatcct gaagttagga aacctgctgc cctacagtga tcccagcgtg gtgtttgtct   2100  
               
               
                   
               
               
                 tcctgtccgt gtttgctgtg gtgacaatcc tgcagtgctt cctgattagc acactcttct   2160  
               
               
                   
               
               
                 ccagagccaa cctggcagca gcctgtgggg gcatcatcta cttcacgctg tacctgccct   2220  
               
               
                   
               
               
                 acgtcctgtg tgtggcatgg caggactacg tgggcttcac actcaagatc ttcgctagcc   2280  
               
               
                   
               
               
                 tgctgtctcc tgtggctttt gggtttggct gtgagtactt tgcccttttt gaggagcagg   2340  
               
               
                   
               
               
                 gcattggagt gcagtgggac aacctgtttg agagtcctgt ggaggaagat ggcttcaatc   2400  
               
               
                   
               
               
                 tcaccacttc ggtctccatg atgctgtttg acaccttcct ctatggggtg atgacctggt   2460  
               
               
                   
               
               
                 acattgaggc tgtctttcca ggccagtacg gaattcccag gccctggtat tttccttgca   2520  
               
               
                   
               
               
                 ccaagtccta ctggtttggc gaggaaagtg atgagaagag ccaccctggt tccaaccaga   2580  
               
               
                   
               
               
                 agagaatatc agaaatctgc atggaggagg aacccaccca cttgaagctg ggcgtgtcca   2640  
               
               
                   
               
               
                 ttcagaacct ggtaaaagtc taccgagatg ggatgaaggt ggctgtcgat ggcctggcac   2700  
               
               
                   
               
               
                 tgaattttta tgagggccag atcacctcct tcctgggcca caatggagcg gggaagacga   2760  
               
               
                   
               
               
                 ccaccatgtc aatcctgacc gggttgttcc ccccgacctc gggcaccgcc tacatcctgg   2820  
               
               
                   
               
               
                 gaaaagacat tcgctctgag atgagcacca tccggcagaa cctgggggtc tgtccccagc   2880  
               
               
                   
               
               
                 ataacgtgct gtttgacatg ctgactgtcg aagaacacat ctggttctat gcccgcttga   2940  
               
               
                   
               
               
                 aagggctctc tgagaagcac gtgaaggcgg agatggagca gatggccctg gatgttggtt   3000  
               
               
                   
               
               
                 tgccatcaag caagctgaaa agcaaaacaa gccagctgtc aggtggaatg cagagaaagc   3060  
               
               
                   
               
               
                 tatctgtggc cttggccttt gtcgggggat ctaaggttgt cattctggat gaacccacag   3120  
               
               
                   
               
               
                 ctggtgtgga cccttactcc cgcaggggaa tatgggagct gctgctgaaa taccgacaag   3180  
               
               
                   
               
               
                 gccgcaccat tattctctct acacaccaca tggatgaagc ggacgtcctg ggggacagga   3240  
               
               
                   
               
               
                 ttgccatcat ctcccatggg aagctgtgct gtgtgggctc ctccctgttt ctgaagaacc   3300  
               
               
                   
               
               
                 agctgggaac aggctactac ctgaccttgg tcaagaaaga tgtggaatcc tccctcagtt   3360  
               
               
                   
               
               
                 cctgcagaaa cagtagtagc actgtgtcat acctgaaaaa ggaggacagt gtttctcaga   3420  
               
               
                   
               
               
                 gcagttctga tgctggcctg ggcagcgacc atgagagtga cacgctgacc atcgatgtct   3480  
               
               
                   
               
               
                 ctgctatctc caacctcatc aggaagcatg tgtctgaagc ccggctggtg gaagacatag   3540  
               
               
                   
               
               
                 ggcatgagct gacctatgtg ctgccatatg aagctgctaa ggagggagcc tttgtggaac   3600  
               
               
                   
               
               
                 tctttcatga gattgatgac cggctctcag acctgggcat ttctagttat ggcatctcag   3660  
               
               
                   
               
               
                 agacgaccct ggaagaaata ttcctcaagg tggccgaaga gagtggggtg gatgctgaga   3720  
               
               
                   
               
               
                 cctcagatgg taccttgcca gcaagacgaa acaggcgggc cttcggggac aagcagagct   3780  
               
               
                   
               
               
                 gtcttcgccc gttcactgaa gatgatgctg ctgatccaaa tgattctgac atagacccag   3840  
               
               
                   
               
               
                 aatccagaga gacagacttg ctcagtggga tggatggcaa agggtcctac caggtgaaag   3900  
               
               
                   
               
               
                 gctggaaact tacacagcaa cagtttgtgg cccttttgtg gaagagactg ctaattgcca   3960  
               
               
                   
               
               
                 gacggagtcg gaaaggattt tttgctcaga ttgtcttgcc agctgtgttt gtctgcattg   4020  
               
               
                   
               
               
                 cccttgtgtt cagcctgatc gtgccaccct ttggcaagta ccccagcctg gaacttcagc   4080  
               
               
                   
               
               
                 cctggatgta caacgaacag tacacatttg tcagcaatga tgctcctgag gacacgggaa   4140  
               
               
                   
               
               
                 ccctggaact cttaaacgcc ctcaccaaag accctggctt cgggacccgc tgtatggaag   4200  
               
               
                   
               
               
                 gaaacccaat cccagacacg ccctgccagg caggggagga agagtggacc actgccccag   4260  
               
               
                   
               
               
                 ttccccagac catcatggac ctcttccaga atgggaactg gacaatgcag aacccttcac   4320  
               
               
                   
               
               
                 ctgcatgcca gtgtagcagc gacaaaatca agaagatgct gcctgtgtgt cccccagggg   4380  
               
               
                   
               
               
                 caggggggct gcctcctcca caaagaaaac aaaacactgc agatatcctt caggacctga   4440  
               
               
                   
               
               
                 caggaagaaa catttcggat tatctggtga agacgtatgt gcagatcata gccaaaagct   4500  
               
               
                   
               
               
                 taaagaacaa gatctgggtg aatgagttta ggtatggcgg cttttccctg ggtgtcagta   4560  
               
               
                   
               
               
                 atactcaagc acttcctccg agtcaagaag ttaatgatgc catcaaacaa atgaagaaac   4620  
               
               
                   
               
               
                 acctaaagct ggccaaggac agttctgcag atcgatttct caacagcttg ggaagattta   4680  
               
               
                   
               
               
                 tgacaggact ggacaccaaa aataatgtca aggtgtggtt caataacaag ggctggcatg   4740  
               
               
                   
               
               
                 caatcagctc tttcctgaat gtcatcaaca atgccattct ccgggccaac ctgcaaaagg   4800  
               
               
                   
               
               
                 gagagaaccc tagccattat ggaattactg ctttcaatca tcccctgaat ctcaccaagc   4860  
               
               
                   
               
               
                 agcagctctc agaggtggct cggatgacca catcagtgga tgtccttgtg tccatctgtg   4920  
               
               
                   
               
               
                 tcatctttgc aatgtccttc gtcccagcca gctttgtcgt attcctgatc caggagcggg   4980  
               
               
                   
               
               
                 tcagcaaagc aaaacacctg cagttcatca gtggagtga agc ctg tca tct act      5034  
               
               
                                                            Ser Leu Ser Ser Thr  
               
               
                                                             1               5  
               
               
                   
               
               
                 ggc tct cta att ttg tct ggg ata tgt gca att aag ttg ttt cca ann     5082  
               
               
                 Gly Ser Leu Ile Leu Ser Gly Ile Cys Ala Ile Lys Leu Phe Pro Xaa  
               
               
                                  10                  15                  20  
               
               
                   
               
               
                 nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn     5130  
               
               
                 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa  
               
               
                              25                  30                  35  
               
               
                   
               
               
                 nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn nnn     5178  
               
               
                 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa  
               
               
                          40                  45                  50  
               
               
                   
               
               
                 nta atc ttt cct ttt cag tgc ttt ggg ctc ctg gga gtt aat ggg gct     5226  
               
               
                 Xaa Ile Phe Pro Phe Gln Cys Phe Gly Leu Leu Gly Val Asn Gly Ala  
               
               
                      55                  60                  65  
               
               
                   
               
               
                 gga aaa tca tca act ttc aag atg tta aca gga gat acc act gtt acc     5274  
               
               
                 Gly Lys Ser Ser Thr Phe Lys Met Leu Thr Gly Asp Thr Thr Val Thr  
               
               
                  70                  75                  80                  85  
               
               
                   
               
               
                 aga gga gat gct ttc ctt aac att tgc agt atc tta tca aac atc cat     5322  
               
               
                 Arg Gly Asp Ala Phe Leu Asn Ile Cys Ser Ile Leu Ser Asn Ile His  
               
               
                                  90                  95                 100  
               
               
                   
               
               
                 gaa gta cat cag aac atg ggc tac tgc cct cag ttt gat gcc atc aca     5370  
               
               
                 Glu Val His Gln Asn Met Gly Tyr Cys Pro Gln Phe Asp Ala Ile Thr  
               
               
                             105                 110                 115  
               
               
                   
               
               
                 gag ctg ttg act ggg aga gaa cac gtg gag ttc ttt gcc ctt ttg aga     5418  
               
               
                 Glu Leu Leu Thr Gly Arg Glu His Val Glu Phe Phe Ala Leu Leu Arg  
               
               
                         120                 125                 130  
               
               
                   
               
               
                 gga gtc cca gag aaa gaa gtt ggc aag gtt ggt gag tgg gcg att cgg     5466  
               
               
                 Gly Val Pro Glu Lys Glu Val Gly Lys Val Gly Glu Trp Ala Ile Arg  
               
               
                     135                 140                 145  
               
               
                   
               
               
                 aaa ctg ggc ctc gtg aag tat gga gaa aaa tat gct ggt aac tat agt     5514  
               
               
                 Lys Leu Gly Leu Val Lys Tyr Gly Glu Lys Tyr Ala Gly Asn Tyr Ser  
               
               
                 150                 155                 160                 165  
               
               
                   
               
               
                 gga ggc aac aaa cgc aag ctc tct aca gcc atg gct ttg atc ggc ggg     5562  
               
               
                 Gly Gly Asn Lys Arg Lys Leu Ser Thr Ala Met Ala Leu Ile Gly Gly  
               
               
                                 170                 175                 180  
               
               
                   
               
               
                 cct cct gtg gtg ttt ctg gat gaa ccc acc aca ggc atg gat ccc aaa     5610  
               
               
                 Pro Pro Val Val Phe Leu Asp Glu Pro Thr Thr Gly Met Asp Pro Lys  
               
               
                             185                 190                 195  
               
               
                   
               
               
                 gcc cgg cgg ttc ttg tgg aat tgt gcc cta agt gtt gtc aag gag ggg     5658  
               
               
                 Ala Arg Arg Phe Leu Trp Asn Cys Ala Leu Ser Val Val Lys Glu Gly  
               
               
                         200                 205                 210  
               
               
                   
               
               
                 aga tca gta gtg ctt aca tct cat agt atg gaa gaa tgt gaa gct ctt     5706  
               
               
                 Arg Ser Val Val Leu Thr Ser His Ser Met Glu Glu Cys Glu Ala Leu  
               
               
                     215                 220                 225  
               
               
                   
               
               
                 tgc act agg atg gca atc atg gtc aat gga agg ttc agg tgc ctt ggc     5754  
               
               
                 Cys Thr Arg Met Ala Ile Met Val Asn Gly Arg Phe Arg Cys Leu Gly  
               
               
                 230                 235                 240                 245  
               
               
                   
               
               
                 agt gtc cag cat cta aaa aat agg ttt gga gat ggt tat aca ata gtt     5802  
               
               
                 Ser Val Gln His Leu Lys Asn Arg Phe Gly Asp Gly Tyr Thr Ile Val  
               
               
                                 250                 255                 260  
               
               
                   
               
               
                 gta cga ata gca ggg tcc aac ccg gac ctg aag cct gtc cag gat ttc     5850  
               
               
                 Val Arg Ile Ala Gly Ser Asn Pro Asp Leu Lys Pro Val Gln Asp Phe  
               
               
                             265                 270                 275  
               
               
                   
               
               
                 ttt gga ctt gca ttt cct gga agt gtt cta aaa gag aaa cac cgg aac     5898  
               
               
                 Phe Gly Leu Ala Phe Pro Gly Ser Val Leu Lys Glu Lys His Arg Asn  
               
               
                         280                 285                 290  
               
               
                   
               
               
                 atg cta caa tac cag ctt cca tct tca tta tct tct ctg gcc agg ata     5946  
               
               
                 Met Leu Gln Tyr Gln Leu Pro Ser Ser Leu Ser Ser Leu Ala Arg Ile  
               
               
                     295                 300                 305  
               
               
                   
               
               
                 ttc agc atc ctc tcc cag agc aaa aag cga ctc cac ata gaa gac tac     5994  
               
               
                 Phe Ser Ile Leu Ser Gln Ser Lys Lys Arg Leu His Ile Glu Asp Tyr  
               
               
                 310                 315                 320                 325  
               
               
                   
               
               
                 tct gtt tct cag aca aca ctt gac caa gta ttt gtg aac ttt gcc aag     6042  
               
               
                 Ser Val Ser Gln Thr Thr Leu Asp Gln Val Phe Val Asn Phe Ala Lys  
               
               
                                 330                 335                 340  
               
               
                   
               
               
                 gac caa agt gat gat gac cac tta aaa gac ctc tca tta cac aaa aac     6090  
               
               
                 Asp Gln Ser Asp Asp Asp His Leu Lys Asp Leu Ser Leu His Lys Asn  
               
               
                             345                 350                 355  
               
               
                   
               
               
                 cag aca gta gtg gac gtt gca gtt ctc aca tct ttt cta cag gat gag     6138  
               
               
                 Gln Thr Val Val Asp Val Ala Val Leu Thr Ser Phe Leu Gln Asp Glu  
               
               
                         360                 365                 370  
               
               
                   
               
               
                 aaa gtg aaa gaa agc tat gta tga agaatcctgt tcatacgggg tggctgaaag    6192  
               
               
                 Lys Val Lys Glu Ser Tyr Val  *  
               
               
                     375                 380  
               
               
                   
               
               
                 taaagaggaa ctagactttc ctttgcacca tgtgaagtgt tgtggagaaa agagccagaa   6252  
               
               
                   
               
               
                 gttgatgtgg gaagaagtaa actggatact gtactgatac tattcaatgc aatgcaattc   6312  
               
               
                   
               
               
                 aatgcaatga aaacaaaatt ccattacagg ggcagtgcct ttgtagccta tgtcttgtat   6372  
               
               
                   
               
               
                 ggctctcaag tgaaagactt gaatttagtt ttttacctat acctatgtga aactctatta   6432  
               
               
                   
               
               
                 tggaacccaa tggacatatg ggtttgaact cacacttttt tttttttttt tgttcctgtg   6492  
               
               
                   
               
               
                 tattctcatt ggggttgcaa caataattca tcaagtaatc atggccagcg attattgatc   6552  
               
               
                   
               
               
                 aaaatcaaaa ggtaatgcac atcctcattc actaagccat gccatgccca ggagactggt   6612  
               
               
                   
               
               
                 ttcccggtga cacatccatt gctggcaatg agtgtgccag agttattagt gccaagtttt   6672  
               
               
                   
               
               
                 tcagaaagtt tgaagcacca tggtgtgtca tgctcacttt tgtgaaagct gctctgctca   6732  
               
               
                   
               
               
                 gagtctatca acattgaata tcagttgaca gaatggtgcc atgcgtggct aacatcctgc   6792  
               
               
                   
               
               
                 tttgattccc tctgataagc tgttctggtg gcagtaacat gcaacaaaaa tgtgggtgtc   6852  
               
               
                   
               
               
                 tccaggcacg ggaaacttgg ttccattgtt atattgtcct atgcttcgag ccatgggtct   6912  
               
               
                   
               
               
                 acagggtcat ccttatgaga ctcttaaata tacttagatc ctggtaagag gcaaagaatc   6972  
               
               
                   
               
               
                 aacagccaaa ctgctggggc tgcaagctgc tgaagccagg gcatgggatt aaagagattg   7032  
               
               
                   
               
               
                 tgcgttcaaa cctagggaag cctgtgccca tttgtcctga ctgtctgcta acatggtaca   7092  
               
               
                   
               
               
                 ctgcatctca agatgtttat ctgacacaag tgtattattt ctggcttttt gaattaatct   7152  
               
               
                   
               
               
                 agaaaatgaa aagatggagt tgtattttga caaaaatgtt tgtacttttt aatgttattt   7212  
               
               
                   
               
               
                 ggaattttaa gttctatcag tgacttctga atccttagaa tggcctcttt gtagaaccct   7272  
               
               
                   
               
               
                 gtggtataga ggagtatggc cactgcccca ctatttttat tttcttatgt aagtttgcat   7332  
               
               
                   
               
               
                 atcagtcatg actagtgcct agaaagcaat gtgatggtca ggatctcatg acattatatt   7392  
               
               
                   
               
               
                 tgagtttctt tcagatcatt taggatactc ttaatctcac ttcatcaatc aaatattttt   7452  
               
               
                   
               
               
                 tgagtgtatg ctgtagctga aagagtatgt acgtacgtat aagactagag agatattaag   7512  
               
               
                   
               
               
                 tctcagtaca cttcctgtgc catgttattc agctcactgg tttacaaata taggttgtct   7572  
               
               
                   
               
               
                 tgtggttgta ggagcccact gtaacaatac tgggcagcct tttttttttt ttttttaatt   7632  
               
               
                   
               
               
                 gcaacaatgc aaaagccaag aaagtataag ggtcacaagt ctaaacaatg aattcttcaa   7692  
               
               
                   
               
               
                 cagggaaaac agctagcttg aaaacttgct gaaaaacaca acttgtgttt atggcattta   7752  
               
               
                   
               
               
                 gtaccttcaa ataattggct ttgcagatat tggatacccc attaaatctg acagtctcaa   7812  
               
               
                   
               
               
                 atttttcatc tcttcaatca ctagtcaaga aaaatataaa aacaacaaat acttccatat   7872  
               
               
                   
               
               
                 ggagcatttt tcagagtttt ctaacccagt cttatttttc tagtcagtaa acatttgtaa   7932  
               
               
                   
               
               
                 aaatactgtt tcactaatac ttactgttaa ctgtcttgag agaaaagaaa aatatgagag   7992  
               
               
                   
               
               
                 aactattgtt tggggaagtt caagtgatct ttcaatatca ttactaactt cttccacttt   8052  
               
               
                   
               
               
                 ttccagaatt tgaatattaa cgctaaaggt gtaagacttc agatttcaaa ttaatctttc   8112  
               
               
                   
               
               
                 tatatttttt aaatttacag aatattatat aacccactgc tgaaaaagaa aaaaatgatt   8172  
               
               
                   
               
               
                 gttttagaag ttaaagtcaa tattgatttt aaatataagt aatgaaggca tatttccaat   8232  
               
               
                   
               
               
                 aactagtgat atggcatcgt tgcattttac agtatcttca aaaatacaga atttatagaa   8292  
               
               
                   
               
               
                 taatttctcc tcatttaata tttttcaaaa tcaaagttat ggtttcctca ttttactaaa   8352  
               
               
                   
               
               
                 atcgtattct aattcttcat tatagtaaat ctatgagcaa ctccttactt cggttcctct   8412  
               
               
                   
               
               
                 gatttcaagg ccatatttta aaaaatcaaa aggcactgtg aactattttg aagaaaacac   8472  
               
               
                   
               
               
                 aacattttaa tacagattga aaggacctct tctgaagcta gaaacaatct atagttatac   8532  
               
               
                   
               
               
                 atcttcatta atactgtgtt accttttaaa atagtaattt tttacatttt cctgtgtaaa   8592  
               
               
                   
               
               
                 cctaattgtg gtagaaattt ttaccaactc tatactcaat caagcaaaat ttctgtatat   8652  
               
               
                   
               
               
                 tccctgtgga atgtacctat gtgagtttca gaaattctca aaatacgtgt tcaaaaattt   8712  
               
               
                   
               
               
                 ctgcttttgc atctttggga cacctcagaa aacttattaa caactgtgaa tatgagaaat   8772  
               
               
                   
               
               
                 acagaagaaa ataataagcc ctctatacat aaatgcccag cacaattcat tgttaaaaaa   8832  
               
               
                   
               
               
                 caaccaaacc tcacactact gtatttcatt atctgtactg aaagcaaatg ctttgtgact   8892  
               
               
                   
               
               
                 attaaatgtt gcacatcatt cattcactgt ata                                8925  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 28  
               
               
                 &lt;211&gt; LENGTH: 380  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: VARIANT  
               
               
                 &lt;222&gt; LOCATION: 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,  
               
               
                       34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,  
               
               
                       50, 51, 52, 53, 54  
               
               
                 &lt;223&gt; OTHER INFORMATION: Xaa = Any Amino Acid  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 28  
               
               
                   
               
               
                 Ser Leu Ser Ser Thr Gly Ser Leu Ile Leu Ser Gly Ile Cys Ala Ile  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Lys Leu Phe Pro Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Xaa Xaa Xaa Xaa Xaa Xaa Ile Phe Pro Phe Gln Cys Phe Gly Leu Leu  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gly Val Asn Gly Ala Gly Lys Ser Ser Thr Phe Lys Met Leu Thr Gly  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Asp Thr Thr Val Thr Arg Gly Asp Ala Phe Leu Asn Ile Cys Ser Ile  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Leu Ser Asn Ile His Glu Val His Gln Asn Met Gly Tyr Cys Pro Gln  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Phe Asp Ala Ile Thr Glu Leu Leu Thr Gly Arg Glu His Val Glu Phe  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Phe Ala Leu Leu Arg Gly Val Pro Glu Lys Glu Val Gly Lys Val Gly  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Glu Trp Ala Ile Arg Lys Leu Gly Leu Val Lys Tyr Gly Glu Lys Tyr  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ala Gly Asn Tyr Ser Gly Gly Asn Lys Arg Lys Leu Ser Thr Ala Met  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ala Leu Ile Gly Gly Pro Pro Val Val Phe Leu Asp Glu Pro Thr Thr  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Gly Met Asp Pro Lys Ala Arg Arg Phe Leu Trp Asn Cys Ala Leu Ser  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Val Val Lys Glu Gly Arg Ser Val Val Leu Thr Ser His Ser Met Glu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Glu Cys Glu Ala Leu Cys Thr Arg Met Ala Ile Met Val Asn Gly Arg  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Phe Arg Cys Leu Gly Ser Val Gln His Leu Lys Asn Arg Phe Gly Asp  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Gly Tyr Thr Ile Val Val Arg Ile Ala Gly Ser Asn Pro Asp Leu Lys  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Pro Val Gln Asp Phe Phe Gly Leu Ala Phe Pro Gly Ser Val Leu Lys  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Glu Lys His Arg Asn Met Leu Gln Tyr Gln Leu Pro Ser Ser Leu Ser  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Ser Leu Ala Arg Ile Phe Ser Ile Leu Ser Gln Ser Lys Lys Arg Leu  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 His Ile Glu Asp Tyr Ser Val Ser Gln Thr Thr Leu Asp Gln Val Phe  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Val Asn Phe Ala Lys Asp Gln Ser Asp Asp Asp His Leu Lys Asp Leu  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ser Leu His Lys Asn Gln Thr Val Val Asp Val Ala Val Leu Thr Ser  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Phe Leu Gln Asp Glu Lys Val Lys Glu Ser Tyr Val  
               
               
                     370                 375                 380  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 29  
               
               
                 &lt;211&gt; LENGTH: 897  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (39)...(842)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding apolipoprotein  
               
               
                       A-1 (APOA1)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 29  
               
               
                   
               
               
                 agagactgcg agaaggaggt cccccacggc ccttcagg atg aaa gct gcg gtg ctg     56  
               
               
                                                           Met Lys Ala Ala Val Leu  
               
               
                                                            1               5  
               
               
                   
               
               
                 acc ttg gcc gtg ctc ttc ctg acg ggg agc cag gct cgg cat ttc tgg      104  
               
               
                 Thr Leu Ala Val Leu Phe Leu Thr Gly Ser Gln Ala Arg His Phe Trp  
               
               
                              10                  15                  20  
               
               
                   
               
               
                 cag caa gat gaa ccc ccc cag agc ccc tgg gat cga gtg aag gac ctg      152  
               
               
                 Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp Asp Arg Val Lys Asp Leu  
               
               
                          25                  30                  35  
               
               
                   
               
               
                 gcc act gtg tac gtg gat gtg ctc aaa gac agc ggc aga gac tat gtg      200  
               
               
                 Ala Thr Val Tyr Val Asp Val Leu Lys Asp Ser Gly Arg Asp Tyr Val  
               
               
                      40                  45                  50  
               
               
                   
               
               
                 tcc cag ttt gaa ggc tcc gcc ttg gga aaa cag cta aac cta aag ctc      248  
               
               
                 Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys Gln Leu Asn Leu Lys Leu  
               
               
                  55                  60                  65                  70  
               
               
                   
               
               
                 ctt gac aac tgg gac agc gtg acc tcc acc ttc agc aag ctg cgc gaa      296  
               
               
                 Leu Asp Asn Trp Asp Ser Val Thr Ser Thr Phe Ser Lys Leu Arg Glu  
               
               
                                  75                  80                  85  
               
               
                   
               
               
                 cag ctc ggc cct gtg acc cag gag ttc tgg gat aac ctg gaa aag gag      344  
               
               
                 Gln Leu Gly Pro Val Thr Gln Glu Phe Trp Asp Asn Leu Glu Lys Glu  
               
               
                              90                  95                 100  
               
               
                   
               
               
                 aca gag ggc ctg agg cag gag atg agc aag gat ctg gag gag gtg aag      392  
               
               
                 Thr Glu Gly Leu Arg Gln Glu Met Ser Lys Asp Leu Glu Glu Val Lys  
               
               
                         105                 110                 115  
               
               
                   
               
               
                 gcc aag gtg cag ccc tac ctg gac gac ttc cag aag aag tgg cag gag      440  
               
               
                 Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe Gln Lys Lys Trp Gln Glu  
               
               
                     120                 125                 130  
               
               
                   
               
               
                 gag atg gag ctc tac cgc cag aag gtg gag ccg ctg cgc gca gag ctc      488  
               
               
                 Glu Met Glu Leu Tyr Arg Gln Lys Val Glu Pro Leu Arg Ala Glu Leu  
               
               
                 135                 140                 145                 150  
               
               
                   
               
               
                 caa gag ggc gcg cgc cag aag ctg cac gag ctg caa gag aag ctg agc      536  
               
               
                 Gln Glu Gly Ala Arg Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser  
               
               
                                 155                 160                 165  
               
               
                   
               
               
                 cca ctg ggc gag gag atg cgc gac cgc gcg cgc gcc cat gtg gac gcg      584  
               
               
                 Pro Leu Gly Glu Glu Met Arg Asp Arg Ala Arg Ala His Val Asp Ala  
               
               
                             170                 175                 180  
               
               
                   
               
               
                 ctg cgc acg cat ctg gcc ccc tac agc gac gag ctg cgc cag cgc ttg      632  
               
               
                 Leu Arg Thr His Leu Ala Pro Tyr Ser Asp Glu Leu Arg Gln Arg Leu  
               
               
                         185                 190                 195  
               
               
                   
               
               
                 gcc gcg cgc ctt gag gct ctc aag gag aac ggc ggc gcc aga ctg gcc      680  
               
               
                 Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn Gly Gly Ala Arg Leu Ala  
               
               
                     200                 205                 210  
               
               
                   
               
               
                 gag tac cac gcc aag gcc acc gag cat ctg agc acg ctc agc gag aag      728  
               
               
                 Glu Tyr His Ala Lys Ala Thr Glu His Leu Ser Thr Leu Ser Glu Lys  
               
               
                 215                 220                 225                 230  
               
               
                   
               
               
                 gcc aag ccc gcg ctc gag gac ctc cgc caa ggc ctg ctg ccc gtg ctg      776  
               
               
                 Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln Gly Leu Leu Pro Val Leu  
               
               
                                 235                 240                 245  
               
               
                   
               
               
                 gag agc ttc aag gtc agc ttc ctg agc gct ctc gag gag tac act aag      824  
               
               
                 Glu Ser Phe Lys Val Ser Phe Leu Ser Ala Leu Glu Glu Tyr Thr Lys  
               
               
                             250                 255                 260  
               
               
                   
               
               
                 aag ctc aac acc cag tga ggcgcccgcc gccgcccccc ttcccggtgc             872  
               
               
                 Lys Leu Asn Thr Gln  *  
               
               
                         265  
               
               
                   
               
               
                 tcagaataaa cgtttccaaa gtggg                                          897  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 30  
               
               
                 &lt;211&gt; LENGTH: 267  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 30  
               
               
                   
               
               
                 Met Lys Ala Ala Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln  
               
               
                             260                 265  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 31  
               
               
                 &lt;211&gt; LENGTH: 14121  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (129)...(13820)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding apolipoprotein B  
               
               
                       (APOB)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 31  
               
               
                   
               
               
                 attcccaccg ggacctgcgg ggctgagtgc ccttctcggt tgctgccgct gaggagcccg     60  
               
               
                   
               
               
                 cccagccagc cagggccgcg aggccgaggc caggccgcag cccaggagcc gccccaccgc    120  
               
               
                   
               
               
                 agctggcg atg gac ccg ccg agg ccc gcg ctg ctg gcg ctg ctg gcg ctg     170  
               
               
                          Met Asp Pro Pro Arg Pro Ala Leu Leu Ala Leu Leu Ala Leu  
               
               
                           1               5                   10  
               
               
                   
               
               
                 cct gcg ctg ctg ctg ctg ctg ctg gcg ggc gcc agg gcc gaa gag gaa      218  
               
               
                 Pro Ala Leu Leu Leu Leu Leu Leu Ala Gly Ala Arg Ala Glu Glu Glu  
               
               
                  15                  20                  25                  30  
               
               
                   
               
               
                 atg ctg gaa aat gtc agc ctg gtc tgt cca aaa gat gcg acc cga ttc      266  
               
               
                 Met Leu Glu Asn Val Ser Leu Val Cys Pro Lys Asp Ala Thr Arg Phe  
               
               
                                  35                  40                  45  
               
               
                   
               
               
                 aag cac ctc cgg aag tac aca tac aac tat gag gct gag agt tcc agt      314  
               
               
                 Lys His Leu Arg Lys Tyr Thr Tyr Asn Tyr Glu Ala Glu Ser Ser Ser  
               
               
                              50                  55                  60  
               
               
                   
               
               
                 gga gtc cct ggg act gct gat tca aga agt gcc acc agg atc aac tgc      362  
               
               
                 Gly Val Pro Gly Thr Ala Asp Ser Arg Ser Ala Thr Arg Ile Asn Cys  
               
               
                          65                  70                  75  
               
               
                   
               
               
                 aag gtt gag ctg gag gtt ccc cag ctc tgc agc ttc atc ctg aag acc      410  
               
               
                 Lys Val Glu Leu Glu Val Pro Gln Leu Cys Ser Phe Ile Leu Lys Thr  
               
               
                      80                  85                  90  
               
               
                   
               
               
                 agc cag tgc acc ctg aaa gag gtg tat ggc ttc aac cct gag ggc aaa      458  
               
               
                 Ser Gln Cys Thr Leu Lys Glu Val Tyr Gly Phe Asn Pro Glu Gly Lys  
               
               
                  95                 100                 105                 110  
               
               
                   
               
               
                 gcc ttg ctg aag aaa acc aag aac tct gag gag ttt gct gca gcc atg      506  
               
               
                 Ala Leu Leu Lys Lys Thr Lys Asn Ser Glu Glu Phe Ala Ala Ala Met  
               
               
                                 115                 120                 125  
               
               
                   
               
               
                 tcc agg tat gag ctc aag ctg gcc att cca gaa ggg aag cag gtt ttc      554  
               
               
                 Ser Arg Tyr Glu Leu Lys Leu Ala Ile Pro Glu Gly Lys Gln Val Phe  
               
               
                             130                 135                 140  
               
               
                   
               
               
                 ctt tac ccg gag aaa gat gaa cct act tac atc ctg aac atc aag agg      602  
               
               
                 Leu Tyr Pro Glu Lys Asp Glu Pro Thr Tyr Ile Leu Asn Ile Lys Arg  
               
               
                         145                 150                 155  
               
               
                   
               
               
                 ggc atc att tct gcc ctc ctg gtt ccc cca gag aca gaa gaa gcc aag      650  
               
               
                 Gly Ile Ile Ser Ala Leu Leu Val Pro Pro Glu Thr Glu Glu Ala Lys  
               
               
                     160                 165                 170  
               
               
                   
               
               
                 caa gtg ttg ttt ctg gat acc gtg tat gga aac tgc tcc act cac ttt      698  
               
               
                 Gln Val Leu Phe Leu Asp Thr Val Tyr Gly Asn Cys Ser Thr His Phe  
               
               
                 175                 180                 185                 190  
               
               
                   
               
               
                 acc gtc aag acg agg aag ggc aat gtg gca aca gaa ata tcc act gaa      746  
               
               
                 Thr Val Lys Thr Arg Lys Gly Asn Val Ala Thr Glu Ile Ser Thr Glu  
               
               
                                 195                 200                 205  
               
               
                   
               
               
                 aga gac ctg ggg cag tgt gat cgc ttc aag ccc atc cgc aca ggc atc      794  
               
               
                 Arg Asp Leu Gly Gln Cys Asp Arg Phe Lys Pro Ile Arg Thr Gly Ile  
               
               
                             210                 215                 220  
               
               
                   
               
               
                 agc cca ctt gct ctc atc aaa ggc atg acc cgc ccc ttg tca act ctg      842  
               
               
                 Ser Pro Leu Ala Leu Ile Lys Gly Met Thr Arg Pro Leu Ser Thr Leu  
               
               
                         225                 230                 235  
               
               
                   
               
               
                 atc agc agc agc cag tcc tgt cag tac aca ctg gac gct aag agg aag      890  
               
               
                 Ile Ser Ser Ser Gln Ser Cys Gln Tyr Thr Leu Asp Ala Lys Arg Lys  
               
               
                     240                 245                 250  
               
               
                   
               
               
                 cat gtg gca gaa gcc atc tgc aag gag caa cac ctc ttc ctg cct ttc      938  
               
               
                 His Val Ala Glu Ala Ile Cys Lys Glu Gln His Leu Phe Leu Pro Phe  
               
               
                 255                 260                 265                 270  
               
               
                   
               
               
                 tcc tac aac aat aag tat ggg atg gta gca caa gtg aca cag act ttg      986  
               
               
                 Ser Tyr Asn Asn Lys Tyr Gly Met Val Ala Gln Val Thr Gln Thr Leu  
               
               
                                 275                 280                 285  
               
               
                   
               
               
                 aaa ctt gaa gac aca cca aag atc aac agc cgc ttc ttt ggt gaa ggt     1034  
               
               
                 Lys Leu Glu Asp Thr Pro Lys Ile Asn Ser Arg Phe Phe Gly Glu Gly  
               
               
                             290                 295                 300  
               
               
                   
               
               
                 act aag aag atg ggc ctc gca ttt gag agc acc aaa tcc aca tca cct     1082  
               
               
                 Thr Lys Lys Met Gly Leu Ala Phe Glu Ser Thr Lys Ser Thr Ser Pro  
               
               
                         305                 310                 315  
               
               
                   
               
               
                 cca aag cag gcc gaa gct gtt ttg aag act ctc cag gaa ctg aaa aaa     1130  
               
               
                 Pro Lys Gln Ala Glu Ala Val Leu Lys Thr Leu Gln Glu Leu Lys Lys  
               
               
                     320                 325                 330  
               
               
                   
               
               
                 cta acc atc tct gag caa aat atc cag aga gct aat ctc ttc aat aag     1178  
               
               
                 Leu Thr Ile Ser Glu Gln Asn Ile Gln Arg Ala Asn Leu Phe Asn Lys  
               
               
                 335                 340                 345                 350  
               
               
                   
               
               
                 ctg gtt act gag ctg aga ggc ctc agt gat gaa gca gtc aca tct ctc     1226  
               
               
                 Leu Val Thr Glu Leu Arg Gly Leu Ser Asp Glu Ala Val Thr Ser Leu  
               
               
                                 355                 360                 365  
               
               
                   
               
               
                 ttg cca cag ctg att gag gtg tcc agc ccc atc act tta caa gcc ttg     1274  
               
               
                 Leu Pro Gln Leu Ile Glu Val Ser Ser Pro Ile Thr Leu Gln Ala Leu  
               
               
                             370                 375                 380  
               
               
                   
               
               
                 gtt cag tgt gga cag cct cag tgc tcc act cac atc ctc cag tgg ctg     1322  
               
               
                 Val Gln Cys Gly Gln Pro Gln Cys Ser Thr His Ile Leu Gln Trp Leu  
               
               
                         385                 390                 395  
               
               
                   
               
               
                 aaa cgt gtg cat gcc aac ccc ctt ctg ata gat gtg gtc acc tac ctg     1370  
               
               
                 Lys Arg Val His Ala Asn Pro Leu Leu Ile Asp Val Val Thr Tyr Leu  
               
               
                     400                 405                 410  
               
               
                   
               
               
                 gtg gcc ctg atc ccc gag ccc tca gca cag cag ctg cga gag atc ttc     1418  
               
               
                 Val Ala Leu Ile Pro Glu Pro Ser Ala Gln Gln Leu Arg Glu Ile Phe  
               
               
                 415                 420                 425                 430  
               
               
                   
               
               
                 aac atg gcg agg gat cag cgc agc cga gcc acc ttg tat gcg ctg agc     1466  
               
               
                 Asn Met Ala Arg Asp Gln Arg Ser Arg Ala Thr Leu Tyr Ala Leu Ser  
               
               
                                 435                 440                 445  
               
               
                   
               
               
                 cac gcg gtc aac aac tat cat aag aca aac cct aca ggg acc cag gag     1514  
               
               
                 His Ala Val Asn Asn Tyr His Lys Thr Asn Pro Thr Gly Thr Gln Glu  
               
               
                             450                 455                 460  
               
               
                   
               
               
                 ctg ctg gac att gct aat tac ctg atg gaa cag att caa gat gac tgc     1562  
               
               
                 Leu Leu Asp Ile Ala Asn Tyr Leu Met Glu Gln Ile Gln Asp Asp Cys  
               
               
                         465                 470                 475  
               
               
                   
               
               
                 act ggg gat gaa gat tac acc tat ttg att ctg cgg gtc att gga aat     1610  
               
               
                 Thr Gly Asp Glu Asp Tyr Thr Tyr Leu Ile Leu Arg Val Ile Gly Asn  
               
               
                     480                 485                 490  
               
               
                   
               
               
                 atg ggc caa acc atg gag cag tta act cca gaa ctc aag tct tca atc     1658  
               
               
                 Met Gly Gln Thr Met Glu Gln Leu Thr Pro Glu Leu Lys Ser Ser Ile  
               
               
                 495                 500                 505                 510  
               
               
                   
               
               
                 ctc aaa tgt gtc caa agt aca aag cca tca ctg atg atc cag aaa gct     1706  
               
               
                 Leu Lys Cys Val Gln Ser Thr Lys Pro Ser Leu Met Ile Gln Lys Ala  
               
               
                                 515                 520                 525  
               
               
                   
               
               
                 gcc atc cag gct ctg cgg aaa atg gag cct aaa gac aag gac cag gag     1754  
               
               
                 Ala Ile Gln Ala Leu Arg Lys Met Glu Pro Lys Asp Lys Asp Gln Glu  
               
               
                             530                 535                 540  
               
               
                   
               
               
                 gtt ctt ctt cag act ttc ctt gat gat gct tct ccg gga gat aag cga     1802  
               
               
                 Val Leu Leu Gln Thr Phe Leu Asp Asp Ala Ser Pro Gly Asp Lys Arg  
               
               
                         545                 550                 555  
               
               
                   
               
               
                 ctg gct gcc tat ctt atg ttg atg agg agt cct tca cag gca gat att     1850  
               
               
                 Leu Ala Ala Tyr Leu Met Leu Met Arg Ser Pro Ser Gln Ala Asp Ile  
               
               
                     560                 565                 570  
               
               
                   
               
               
                 aac aaa att gtc caa att cta cca tgg gaa cag aat gag caa gtg aag     1898  
               
               
                 Asn Lys Ile Val Gln Ile Leu Pro Trp Glu Gln Asn Glu Gln Val Lys  
               
               
                 575                 580                 585                 590  
               
               
                   
               
               
                 aac ttt gtg gct tcc cat att gcc aat atc ttg aac tca gaa gaa ttg     1946  
               
               
                 Asn Phe Val Ala Ser His Ile Ala Asn Ile Leu Asn Ser Glu Glu Leu  
               
               
                                 595                 600                 605  
               
               
                   
               
               
                 gat atc caa gat ctg aaa aag tta gtg aaa gaa gct ctg aaa gaa tct     1994  
               
               
                 Asp Ile Gln Asp Leu Lys Lys Leu Val Lys Glu Ala Leu Lys Glu Ser  
               
               
                             610                 615                 620  
               
               
                   
               
               
                 caa ctt cca act gtc atg gac ttc aga aaa ttc tct cgg aac tat caa     2042  
               
               
                 Gln Leu Pro Thr Val Met Asp Phe Arg Lys Phe Ser Arg Asn Tyr Gln  
               
               
                         625                 630                 635  
               
               
                   
               
               
                 ctc tac aaa tct gtt tct ctt cca tca ctt gac cca gcc tca gcc aaa     2090  
               
               
                 Leu Tyr Lys Ser Val Ser Leu Pro Ser Leu Asp Pro Ala Ser Ala Lys  
               
               
                     640                 645                 650  
               
               
                   
               
               
                 ata gaa ggg aat ctt ata ttt gat cca aat aac tac ctt cct aaa gaa     2138  
               
               
                 Ile Glu Gly Asn Leu Ile Phe Asp Pro Asn Asn Tyr Leu Pro Lys Glu  
               
               
                 655                 660                 665                 670  
               
               
                   
               
               
                 agc atg ctg aaa act acc ctc act gcc ttt gga ttt gct tca gct gac     2186  
               
               
                 Ser Met Leu Lys Thr Thr Leu Thr Ala Phe Gly Phe Ala Ser Ala Asp  
               
               
                                 675                 680                 685  
               
               
                   
               
               
                 ctc atc gag att ggc ttg gaa gga aaa ggc ttt gag cca aca ttg gaa     2234  
               
               
                 Leu Ile Glu Ile Gly Leu Glu Gly Lys Gly Phe Glu Pro Thr Leu Glu  
               
               
                             690                 695                 700  
               
               
                   
               
               
                 gct ctt ttt ggg aag caa gga ttt ttc cca gac agt gtc aac aaa gct     2282  
               
               
                 Ala Leu Phe Gly Lys Gln Gly Phe Phe Pro Asp Ser Val Asn Lys Ala  
               
               
                         705                 710                 715  
               
               
                   
               
               
                 ttg tac tgg gtt aat ggt caa gtt cct gat ggt gtc tct aag gtc tta     2330  
               
               
                 Leu Tyr Trp Val Asn Gly Gln Val Pro Asp Gly Val Ser Lys Val Leu  
               
               
                     720                 725                 730  
               
               
                   
               
               
                 gtg gac cac ttt ggc tat acc aaa gat gat aaa cat gag cag gat atg     2378  
               
               
                 Val Asp His Phe Gly Tyr Thr Lys Asp Asp Lys His Glu Gln Asp Met  
               
               
                 735                 740                 745                 750  
               
               
                   
               
               
                 gta aat gga ata atg ctc agt gtt gag aag ctg att aaa gat ttg aaa     2426  
               
               
                 Val Asn Gly Ile Met Leu Ser Val Glu Lys Leu Ile Lys Asp Leu Lys  
               
               
                                 755                 760                 765  
               
               
                   
               
               
                 tcc aaa gaa gtc ccg gaa gcc aga gcc tac ctc cgc atc ttg gga gag     2474  
               
               
                 Ser Lys Glu Val Pro Glu Ala Arg Ala Tyr Leu Arg Ile Leu Gly Glu  
               
               
                             770                 775                 780  
               
               
                   
               
               
                 gag ctt ggt ttt gcc agt ctc cat gac ctc cag ctc ctg gga aag ctg     2522  
               
               
                 Glu Leu Gly Phe Ala Ser Leu His Asp Leu Gln Leu Leu Gly Lys Leu  
               
               
                         785                 790                 795  
               
               
                   
               
               
                 ctt ctg atg ggt gcc cgc act ctg cag ggg atc ccc cag atg att gga     2570  
               
               
                 Leu Leu Met Gly Ala Arg Thr Leu Gln Gly Ile Pro Gln Met Ile Gly  
               
               
                     800                 805                 810  
               
               
                   
               
               
                 gag gtc atc agg aag ggc tca aag aat gac ttt ttt ctt cac tac atc     2618  
               
               
                 Glu Val Ile Arg Lys Gly Ser Lys Asn Asp Phe Phe Leu His Tyr Ile  
               
               
                 815                 820                 825                 830  
               
               
                   
               
               
                 ttc atg gag aat gcc ttt gaa ctc ccc act gga gct gga tta cag ttg     2666  
               
               
                 Phe Met Glu Asn Ala Phe Glu Leu Pro Thr Gly Ala Gly Leu Gln Leu  
               
               
                                 835                 840                 845  
               
               
                   
               
               
                 caa ata tct tca tct gga gtc att gct ccc gga gcc aag gct gga gta     2714  
               
               
                 Gln Ile Ser Ser Ser Gly Val Ile Ala Pro Gly Ala Lys Ala Gly Val  
               
               
                             850                 855                 860  
               
               
                   
               
               
                 aaa ctg gaa gta gcc aac atg cag gct gaa ctg gtg gca aaa ccc tcc     2762  
               
               
                 Lys Leu Glu Val Ala Asn Met Gln Ala Glu Leu Val Ala Lys Pro Ser  
               
               
                         865                 870                 875  
               
               
                   
               
               
                 gtg tct gtg gag ttt gtg aca aat atg ggc atc atc att ccg gac ttc     2810  
               
               
                 Val Ser Val Glu Phe Val Thr Asn Met Gly Ile Ile Ile Pro Asp Phe  
               
               
                     880                 885                 890  
               
               
                   
               
               
                 gct agg agt ggg gtc cag atg aac acc aac ttc ttc cac gag tcg ggt     2858  
               
               
                 Ala Arg Ser Gly Val Gln Met Asn Thr Asn Phe Phe His Glu Ser Gly  
               
               
                 895                 900                 905                 910  
               
               
                   
               
               
                 ctg gag gct cat gtt gcc cta aaa gct ggg aag ctg aag ttt atc att     2906  
               
               
                 Leu Glu Ala His Val Ala Leu Lys Ala Gly Lys Leu Lys Phe Ile Ile  
               
               
                                 915                 920                 925  
               
               
                   
               
               
                 cct tcc cca aag aga cca gtc aag ctg ctc agt gga ggc aac aca tta     2954  
               
               
                 Pro Ser Pro Lys Arg Pro Val Lys Leu Leu Ser Gly Gly Asn Thr Leu  
               
               
                             930                 935                 940  
               
               
                   
               
               
                 cat ttg gtc tct acc acc aaa acg gag gtg atc cca cct ctc att gag     3002  
               
               
                 His Leu Val Ser Thr Thr Lys Thr Glu Val Ile Pro Pro Leu Ile Glu  
               
               
                         945                 950                 955  
               
               
                   
               
               
                 aac agg cag tcc tgg tca gtt tgc aag caa gtc ttt cct ggc ctg aat     3050  
               
               
                 Asn Arg Gln Ser Trp Ser Val Cys Lys Gln Val Phe Pro Gly Leu Asn  
               
               
                     960                 965                 970  
               
               
                   
               
               
                 tac tgc acc tca ggc gct tac tcc aac gcc agc tcc aca gac tcc gcc     3098  
               
               
                 Tyr Cys Thr Ser Gly Ala Tyr Ser Asn Ala Ser Ser Thr Asp Ser Ala  
               
               
                 975                 980                 985                 990  
               
               
                   
               
               
                 tcc tac tat ccg ctg acc ggg gac acc aga tta gag ctg gaa ctg agg     3146  
               
               
                 Ser Tyr Tyr Pro Leu Thr Gly Asp Thr Arg Leu Glu Leu Glu Leu Arg  
               
               
                                  995                1000                1005  
               
               
                   
               
               
                 cct aca gga gag att gag cag tat tct gtc agc gca acc tat gag ctc     3194  
               
               
                 Pro Thr Gly Glu Ile Glu Gln Tyr Ser Val Ser Ala Thr Tyr Glu Leu  
               
               
                             1010                1015                1020  
               
               
                   
               
               
                 cag aga gag gac aga gcc ttg gtg gat acc ctg aag ttt gta act caa     3242  
               
               
                 Gln Arg Glu Asp Arg Ala Leu Val Asp Thr Leu Lys Phe Val Thr Gln  
               
               
                         1025                1030                1035  
               
               
                   
               
               
                 gca gaa ggt gcg aag cag act gag gct acc atg aca ttc aaa tat aat     3290  
               
               
                 Ala Glu Gly Ala Lys Gln Thr Glu Ala Thr Met Thr Phe Lys Tyr Asn  
               
               
                     1040                1045                1050  
               
               
                   
               
               
                 cgg cag agt atg acc ttg tcc agt gaa gtc caa att ccg gat ttt gat     3338  
               
               
                 Arg Gln Ser Met Thr Leu Ser Ser Glu Val Gln Ile Pro Asp Phe Asp  
               
               
                 1055                1060                1065                1070  
               
               
                   
               
               
                 gtt gac ctc gga aca atc ctc aga gtt aat gat gaa tct act gag ggc     3386  
               
               
                 Val Asp Leu Gly Thr Ile Leu Arg Val Asn Asp Glu Ser Thr Glu Gly  
               
               
                                 1075                1080                1085  
               
               
                   
               
               
                 aaa acg tct tac aga ctc acc ctg gac att cag aac aag aaa att act     3434  
               
               
                 Lys Thr Ser Tyr Arg Leu Thr Leu Asp Ile Gln Asn Lys Lys Ile Thr  
               
               
                             1090                1095                1100  
               
               
                   
               
               
                 gag gtc gcc ctc atg ggc cac cta agt tgt gac aca aag gaa gaa aga     3482  
               
               
                 Glu Val Ala Leu Met Gly His Leu Ser Cys Asp Thr Lys Glu Glu Arg  
               
               
                         1105                1110                1115  
               
               
                   
               
               
                 aaa atc aag ggt gtt att tcc ata ccc cgt ttg caa gca gaa gcc aga     3530  
               
               
                 Lys Ile Lys Gly Val Ile Ser Ile Pro Arg Leu Gln Ala Glu Ala Arg  
               
               
                     1120                1125                1130  
               
               
                   
               
               
                 agt gag atc ctc gcc cac tgg tcg cct gcc aaa ctg ctt ctc caa atg     3578  
               
               
                 Ser Glu Ile Leu Ala His Trp Ser Pro Ala Lys Leu Leu Leu Gln Met  
               
               
                 1135                1140                1145                1150  
               
               
                   
               
               
                 gac tca tct gct aca gct tat ggc tcc aca gtt tcc aag agg gtg gca     3626  
               
               
                 Asp Ser Ser Ala Thr Ala Tyr Gly Ser Thr Val Ser Lys Arg Val Ala  
               
               
                                 1155                1160                1165  
               
               
                   
               
               
                 tgg cat tat gat gaa gag aag att gaa ttt gaa tgg aac aca ggc acc     3674  
               
               
                 Trp His Tyr Asp Glu Glu Lys Ile Glu Phe Glu Trp Asn Thr Gly Thr  
               
               
                             1170                1175                1180  
               
               
                   
               
               
                 aat gta gat acc aaa aaa atg act tcc aat ttc cct gtg gat ctc tcc     3722  
               
               
                 Asn Val Asp Thr Lys Lys Met Thr Ser Asn Phe Pro Val Asp Leu Ser  
               
               
                         1185                1190                1195  
               
               
                   
               
               
                 gat tat cct aag agc ttg cat atg tat gct aat aga ctc ctg gat cac     3770  
               
               
                 Asp Tyr Pro Lys Ser Leu His Met Tyr Ala Asn Arg Leu Leu Asp His  
               
               
                     1200                1205                1210  
               
               
                   
               
               
                 aga gtc cct gaa aca gac atg act ttc cgg cac gtg ggt tcc aaa tta     3818  
               
               
                 Arg Val Pro Glu Thr Asp Met Thr Phe Arg His Val Gly Ser Lys Leu  
               
               
                 1215                1220                1225                1230  
               
               
                   
               
               
                 ata gtt gca atg agc tca tgg ctt cag aag gca tct ggg agt ctt cct     3866  
               
               
                 Ile Val Ala Met Ser Ser Trp Leu Gln Lys Ala Ser Gly Ser Leu Pro  
               
               
                                 1235                1240                1245  
               
               
                   
               
               
                 tat acc cag act ttg caa gac cac ctc aat agc ctg aag gag ttc aac     3914  
               
               
                 Tyr Thr Gln Thr Leu Gln Asp His Leu Asn Ser Leu Lys Glu Phe Asn  
               
               
                             1250                1255                1260  
               
               
                   
               
               
                 ctc cag aac atg gga ttg cca gac ttc cac atc cca gaa aac ctc ttc     3962  
               
               
                 Leu Gln Asn Met Gly Leu Pro Asp Phe His Ile Pro Glu Asn Leu Phe  
               
               
                         1265                1270                1275  
               
               
                   
               
               
                 tta aaa agc gat ggc cgg gtc aaa tat acc ttg aac aag aac agt ttg     4010  
               
               
                 Leu Lys Ser Asp Gly Arg Val Lys Tyr Thr Leu Asn Lys Asn Ser Leu  
               
               
                     1280                1285                1290  
               
               
                   
               
               
                 aaa att gag att cct ttg cct ttt ggt ggc aaa tcc tcc aga gat cta     4058  
               
               
                 Lys Ile Glu Ile Pro Leu Pro Phe Gly Gly Lys Ser Ser Arg Asp Leu  
               
               
                 1295                1300                1305                1310  
               
               
                   
               
               
                 aag atg tta gag act gtt agg aca cca gcc ctc cac ttc aag tct gtg     4106  
               
               
                 Lys Met Leu Glu Thr Val Arg Thr Pro Ala Leu His Phe Lys Ser Val  
               
               
                                 1315                1320                1325  
               
               
                   
               
               
                 gga ttc cat ctg cca tct cga gag ttc caa gtc cct act ttt acc att     4154  
               
               
                 Gly Phe His Leu Pro Ser Arg Glu Phe Gln Val Pro Thr Phe Thr Ile  
               
               
                             1330                1335                1340  
               
               
                   
               
               
                 ccc aag ttg tat caa ctg caa gtg cct ctc ctg ggt gtt cta gac ctc     4202  
               
               
                 Pro Lys Leu Tyr Gln Leu Gln Val Pro Leu Leu Gly Val Leu Asp Leu  
               
               
                         1345                1350                1355  
               
               
                   
               
               
                 tcc acg aat gtc tac agc aac ttg tac aac tgg tcc gcc tcc tac agt     4250  
               
               
                 Ser Thr Asn Val Tyr Ser Asn Leu Tyr Asn Trp Ser Ala Ser Tyr Ser  
               
               
                     1360                1365                1370  
               
               
                   
               
               
                 ggt ggc aac acc agc aca gac cat ttc agc ctt cgg gct cgt tac cac     4298  
               
               
                 Gly Gly Asn Thr Ser Thr Asp His Phe Ser Leu Arg Ala Arg Tyr His  
               
               
                 1375                1380                1385                1390  
               
               
                   
               
               
                 atg aag gct gac tct gtg gtt gac ctg ctt tcc tac aat gtg caa gga     4346  
               
               
                 Met Lys Ala Asp Ser Val Val Asp Leu Leu Ser Tyr Asn Val Gln Gly  
               
               
                                 1395                1400                1405  
               
               
                   
               
               
                 tct gga gaa aca aca tat gac cac aag aat acg ttc aca cta tca tgt     4394  
               
               
                 Ser Gly Glu Thr Thr Tyr Asp His Lys Asn Thr Phe Thr Leu Ser Cys  
               
               
                             1410                1415                1420  
               
               
                   
               
               
                 gat ggg tct cta cgc cac aaa ttt cta gat tcg aat atc aaa ttc agt     4442  
               
               
                 Asp Gly Ser Leu Arg His Lys Phe Leu Asp Ser Asn Ile Lys Phe Ser  
               
               
                         1425                1430                1435  
               
               
                   
               
               
                 cat gta gaa aaa ctt gga aac aac cca gtc tca aaa ggt tta cta ata     4490  
               
               
                 His Val Glu Lys Leu Gly Asn Asn Pro Val Ser Lys Gly Leu Leu Ile  
               
               
                     1440                1445                1450  
               
               
                   
               
               
                 ttc gat gca tct agt tcc tgg gga cca cag atg tct gct tca gtt cat     4538  
               
               
                 Phe Asp Ala Ser Ser Ser Trp Gly Pro Gln Met Ser Ala Ser Val His  
               
               
                 1455                1460                1465                1470  
               
               
                   
               
               
                 ttg gac tcc aaa aag aaa cag cat ttg ttt gtc aaa gaa gtc aag att     4586  
               
               
                 Leu Asp Ser Lys Lys Lys Gln His Leu Phe Val Lys Glu Val Lys Ile  
               
               
                                 1475                1480                1485  
               
               
                   
               
               
                 gat ggg cag ttc aga gtc tct tcg ttc tat gct aaa ggc aca tat ggc     4634  
               
               
                 Asp Gly Gln Phe Arg Val Ser Ser Phe Tyr Ala Lys Gly Thr Tyr Gly  
               
               
                             1490                1495                1500  
               
               
                   
               
               
                 ctg tct tgt cag agg gat cct aac act ggc cgg ctc aat gga gag tcc     4682  
               
               
                 Leu Ser Cys Gln Arg Asp Pro Asn Thr Gly Arg Leu Asn Gly Glu Ser  
               
               
                         1505                1510                1515  
               
               
                   
               
               
                 aac ctg agg ttt aac tcc tcc tac ctc caa ggc acc aac cag ata aca     4730  
               
               
                 Asn Leu Arg Phe Asn Ser Ser Tyr Leu Gln Gly Thr Asn Gln Ile Thr  
               
               
                     1520                1525                1530  
               
               
                   
               
               
                 gga aga tat gaa gat gga acc ctc tcc ctc acc tcc acc tct gat ctg     4778  
               
               
                 Gly Arg Tyr Glu Asp Gly Thr Leu Ser Leu Thr Ser Thr Ser Asp Leu  
               
               
                 1535                1540                1545                1550  
               
               
                   
               
               
                 caa agt ggc atc att aaa aat act gct tcc cta aag tat gag aac tac     4826  
               
               
                 Gln Ser Gly Ile Ile Lys Asn Thr Ala Ser Leu Lys Tyr Glu Asn Tyr  
               
               
                                 1555                1560                1565  
               
               
                   
               
               
                 gag ctg act tta aaa tct gac acc aat ggg aag tat aag aac ttt gcc     4874  
               
               
                 Glu Leu Thr Leu Lys Ser Asp Thr Asn Gly Lys Tyr Lys Asn Phe Ala  
               
               
                             1570                1575                1580  
               
               
                   
               
               
                 act tct aac aag atg gat atg acc ttc tct aag caa aat gca ctg ctg     4922  
               
               
                 Thr Ser Asn Lys Met Asp Met Thr Phe Ser Lys Gln Asn Ala Leu Leu  
               
               
                         1585                1590                1595  
               
               
                   
               
               
                 cgt tct gaa tat cag gct gat tac gag tca ttg agg ttc ttc agc ctg     4970  
               
               
                 Arg Ser Glu Tyr Gln Ala Asp Tyr Glu Ser Leu Arg Phe Phe Ser Leu  
               
               
                     1600                1605                1610  
               
               
                   
               
               
                 ctt tct gga tca cta aat tcc cat ggt ctt gag tta aat gct gac atc     5018  
               
               
                 Leu Ser Gly Ser Leu Asn Ser His Gly Leu Glu Leu Asn Ala Asp Ile  
               
               
                 1615                1620                1625                1630  
               
               
                   
               
               
                 tta ggc act gac aaa att aat agt ggt gct cac aag gcg aca cta agg     5066  
               
               
                 Leu Gly Thr Asp Lys Ile Asn Ser Gly Ala His Lys Ala Thr Leu Arg  
               
               
                                 1635                1640                1645  
               
               
                   
               
               
                 att ggc caa gat gga ata tct acc agt gca acg acc aac ttg aag tgt     5114  
               
               
                 Ile Gly Gln Asp Gly Ile Ser Thr Ser Ala Thr Thr Asn Leu Lys Cys  
               
               
                             1650                1655                1660  
               
               
                   
               
               
                 agt ctc ctg gtg ctg gag aat gag ctg aat gca gag ctt ggc ctc tct     5162  
               
               
                 Ser Leu Leu Val Leu Glu Asn Glu Leu Asn Ala Glu Leu Gly Leu Ser  
               
               
                         1665                1670                1675  
               
               
                   
               
               
                 ggg gca tct atg aaa tta aca aca aat ggc cgc ttc agg gaa cac aat     5210  
               
               
                 Gly Ala Ser Met Lys Leu Thr Thr Asn Gly Arg Phe Arg Glu His Asn  
               
               
                     1680                1685                1690  
               
               
                   
               
               
                 gca aaa ttc agt ctg gat ggg aaa gcc gcc ctc aca gag cta tca ctg     5258  
               
               
                 Ala Lys Phe Ser Leu Asp Gly Lys Ala Ala Leu Thr Glu Leu Ser Leu  
               
               
                 1695                1700                1705                1710  
               
               
                   
               
               
                 gga agt gct tat cag gcc atg att ctg ggt gtc gac agc aaa aac att     5306  
               
               
                 Gly Ser Ala Tyr Gln Ala Met Ile Leu Gly Val Asp Ser Lys Asn Ile  
               
               
                                 1715                1720                1725  
               
               
                   
               
               
                 ttc aac ttc aag gtc agt caa gaa gga ctt aag ctc tca aat gac atg     5354  
               
               
                 Phe Asn Phe Lys Val Ser Gln Glu Gly Leu Lys Leu Ser Asn Asp Met  
               
               
                             1730                1735                1740  
               
               
                   
               
               
                 atg ggc tca tat gct gaa atg aaa ttt gac cac aca aac agt ctg aac     5402  
               
               
                 Met Gly Ser Tyr Ala Glu Met Lys Phe Asp His Thr Asn Ser Leu Asn  
               
               
                         1745                1750                1755  
               
               
                   
               
               
                 att gca ggc tta tca ctg gac ttc tct tca aaa ctt gac aac att tac     5450  
               
               
                 Ile Ala Gly Leu Ser Leu Asp Phe Ser Ser Lys Leu Asp Asn Ile Tyr  
               
               
                     1760                1765                1770  
               
               
                   
               
               
                 agc tct gac aag ttt tat aag caa act gtt aat tta cag cta cag ccc     5498  
               
               
                 Ser Ser Asp Lys Phe Tyr Lys Gln Thr Val Asn Leu Gln Leu Gln Pro  
               
               
                 1775                1780                1785                1790  
               
               
                   
               
               
                 tat tct ctg gta act act tta aac agt gac ctg aaa tac aat gct ctg     5546  
               
               
                 Tyr Ser Leu Val Thr Thr Leu Asn Ser Asp Leu Lys Tyr Asn Ala Leu  
               
               
                                 1795                1800                1805  
               
               
                   
               
               
                 gat ctc acc aac aat ggg aaa cta cgg cta gaa ccc ctg aag ctg cat     5594  
               
               
                 Asp Leu Thr Asn Asn Gly Lys Leu Arg Leu Glu Pro Leu Lys Leu His  
               
               
                             1810                1815                1820  
               
               
                   
               
               
                 gtg gct ggt aac cta aaa gga gcc tac caa aat aat gaa ata aaa cac     5642  
               
               
                 Val Ala Gly Asn Leu Lys Gly Ala Tyr Gln Asn Asn Glu Ile Lys His  
               
               
                         1825                1830                1835  
               
               
                   
               
               
                 atc tat gcc atc tct tct gct gcc tta tca gca agc tat aaa gca gac     5690  
               
               
                 Ile Tyr Ala Ile Ser Ser Ala Ala Leu Ser Ala Ser Tyr Lys Ala Asp  
               
               
                     1840                1845                1850  
               
               
                   
               
               
                 act gtt gct aag gtt cag ggt gtg gag ttt agc cat cgg ctc aac aca     5738  
               
               
                 Thr Val Ala Lys Val Gln Gly Val Glu Phe Ser His Arg Leu Asn Thr  
               
               
                 1855                1860                1865                1870  
               
               
                   
               
               
                 gac atc gct ggg ctg gct tca gcc att gac atg agc aca aac tat aat     5786  
               
               
                 Asp Ile Ala Gly Leu Ala Ser Ala Ile Asp Met Ser Thr Asn Tyr Asn  
               
               
                                 1875                1880                1885  
               
               
                   
               
               
                 tca gac tca ctg cat ttc agc aat gtc ttc cgt tct gta atg gcc ccg     5834  
               
               
                 Ser Asp Ser Leu His Phe Ser Asn Val Phe Arg Ser Val Met Ala Pro  
               
               
                             1890                1895                1900  
               
               
                   
               
               
                 ttt acc atg acc atc gat gca cat aca aat ggc aat ggg aaa ctc gct     5882  
               
               
                 Phe Thr Met Thr Ile Asp Ala His Thr Asn Gly Asn Gly Lys Leu Ala  
               
               
                         1905                1910                1915  
               
               
                   
               
               
                 ctc tgg gga gaa cat act ggg cag ctg tat agc aaa ttc ctg ttg aaa     5930  
               
               
                 Leu Trp Gly Glu His Thr Gly Gln Leu Tyr Ser Lys Phe Leu Leu Lys  
               
               
                     1920                1925                1930  
               
               
                   
               
               
                 gca gaa cct ctg gca ttt act ttc tct cat gat tac aaa ggc tcc aca     5978  
               
               
                 Ala Glu Pro Leu Ala Phe Thr Phe Ser His Asp Tyr Lys Gly Ser Thr  
               
               
                 1935                1940                1945                1950  
               
               
                   
               
               
                 agt cat cat ctc gtg tct agg aaa agc atc agt gca gct ctt gaa cac     6026  
               
               
                 Ser His His Leu Val Ser Arg Lys Ser Ile Ser Ala Ala Leu Glu His  
               
               
                                 1955                1960                1965  
               
               
                   
               
               
                 aaa gtc agt gcc ctg ctt act cca gct gag cag aca ggc acc tgg aaa     6074  
               
               
                 Lys Val Ser Ala Leu Leu Thr Pro Ala Glu Gln Thr Gly Thr Trp Lys  
               
               
                             1970                1975                1980  
               
               
                   
               
               
                 ctc aag acc caa ttt aac aac aat gaa tac agc cag gac ttg gat gct     6122  
               
               
                 Leu Lys Thr Gln Phe Asn Asn Asn Glu Tyr Ser Gln Asp Leu Asp Ala  
               
               
                         1985                1990                1995  
               
               
                   
               
               
                 tac aac act aaa gat aaa att ggc gtg gag ctt act gga cga act ctg     6170  
               
               
                 Tyr Asn Thr Lys Asp Lys Ile Gly Val Glu Leu Thr Gly Arg Thr Leu  
               
               
                     2000                2005                2010  
               
               
                   
               
               
                 gct gac cta act cta cta gac tcc cca att aaa gtg cca ctt tta ctc     6218  
               
               
                 Ala Asp Leu Thr Leu Leu Asp Ser Pro Ile Lys Val Pro Leu Leu Leu  
               
               
                 2015                2020                2025                2030  
               
               
                   
               
               
                 agt gag ccc atc aat atc att gat gct tta gag atg aga gat gcc gtt     6266  
               
               
                 Ser Glu Pro Ile Asn Ile Ile Asp Ala Leu Glu Met Arg Asp Ala Val  
               
               
                                 2035                2040                2045  
               
               
                   
               
               
                 gag aag ccc caa gaa ttt aca att gtt gct ttt gta aag tat gat aaa     6314  
               
               
                 Glu Lys Pro Gln Glu Phe Thr Ile Val Ala Phe Val Lys Tyr Asp Lys  
               
               
                             2050                2055                2060  
               
               
                   
               
               
                 aac caa gat gtt cac tcc att aac ctc cca ttt ttt gag acc ttg caa     6362  
               
               
                 Asn Gln Asp Val His Ser Ile Asn Leu Pro Phe Phe Glu Thr Leu Gln  
               
               
                         2065                2070                2075  
               
               
                   
               
               
                 gaa tat ttt gag agg aat cga caa acc att ata gtt gta gtg gaa aac     6410  
               
               
                 Glu Tyr Phe Glu Arg Asn Arg Gln Thr Ile Ile Val Val Val Glu Asn  
               
               
                     2080                2085                2090  
               
               
                   
               
               
                 gta cag aga aac ctg aag cac atc aat att gat caa ttt gta aga aaa     6458  
               
               
                 Val Gln Arg Asn Leu Lys His Ile Asn Ile Asp Gln Phe Val Arg Lys  
               
               
                 2095                2100                2105                2110  
               
               
                   
               
               
                 tac aga gca gcc ctg gga aaa ctc cca cag caa gct aat gat tat ctg     6506  
               
               
                 Tyr Arg Ala Ala Leu Gly Lys Leu Pro Gln Gln Ala Asn Asp Tyr Leu  
               
               
                                 2115                2120                2125  
               
               
                   
               
               
                 aat tca ttc aat tgg gag aga caa gtt tca cat gcc aag gag aaa ctg     6554  
               
               
                 Asn Ser Phe Asn Trp Glu Arg Gln Val Ser His Ala Lys Glu Lys Leu  
               
               
                             2130                2135                2140  
               
               
                   
               
               
                 act gct ctc aca aaa aag tat aga att aca gaa aat gat ata caa att     6602  
               
               
                 Thr Ala Leu Thr Lys Lys Tyr Arg Ile Thr Glu Asn Asp Ile Gln Ile  
               
               
                         2145                2150                2155  
               
               
                   
               
               
                 gca tta gat gat gcc aaa atc aac ttt aat gaa aaa cta tct caa ctg     6650  
               
               
                 Ala Leu Asp Asp Ala Lys Ile Asn Phe Asn Glu Lys Leu Ser Gln Leu  
               
               
                     2160                2165                2170  
               
               
                   
               
               
                 cag aca tat atg ata caa ttt gat cag tat att aaa gat agt tat gat     6698  
               
               
                 Gln Thr Tyr Met Ile Gln Phe Asp Gln Tyr Ile Lys Asp Ser Tyr Asp  
               
               
                 2175                2180                2185                2190  
               
               
                   
               
               
                 tta cat gat ttg aaa ata gct att gct aat att att gat gaa atc att     6746  
               
               
                 Leu His Asp Leu Lys Ile Ala Ile Ala Asn Ile Ile Asp Glu Ile Ile  
               
               
                                 2195                2200                2205  
               
               
                   
               
               
                 gaa aaa tta aaa agt ctt gat gag cac tat cat atc cgt gta aat tta     6794  
               
               
                 Glu Lys Leu Lys Ser Leu Asp Glu His Tyr His Ile Arg Val Asn Leu  
               
               
                             2210                2215                2220  
               
               
                   
               
               
                 gta aaa aca atc cat gat cta cat ttg ttt att gaa aat att gat ttt     6842  
               
               
                 Val Lys Thr Ile His Asp Leu His Leu Phe Ile Glu Asn Ile Asp Phe  
               
               
                         2225                2230                2235  
               
               
                   
               
               
                 aac aaa agt gga agt agt act gca tcc tgg att caa aat gtg gat act     6890  
               
               
                 Asn Lys Ser Gly Ser Ser Thr Ala Ser Trp Ile Gln Asn Val Asp Thr  
               
               
                     2240                2245                2250  
               
               
                   
               
               
                 aag tac caa atc aga atc cag ata caa gaa aaa ctg cag cag ctt aag     6938  
               
               
                 Lys Tyr Gln Ile Arg Ile Gln Ile Gln Glu Lys Leu Gln Gln Leu Lys  
               
               
                 2255                2260                2265                2270  
               
               
                   
               
               
                 aga cac ata cag aat ata gac atc cag cac cta gct gga aag tta aaa     6986  
               
               
                 Arg His Ile Gln Asn Ile Asp Ile Gln His Leu Ala Gly Lys Leu Lys  
               
               
                                 2275                2280                2285  
               
               
                   
               
               
                 caa cac att gag gct att gat gtt aga gtg ctt tta gat caa ttg gga     7034  
               
               
                 Gln His Ile Glu Ala Ile Asp Val Arg Val Leu Leu Asp Gln Leu Gly  
               
               
                             2290                2295                2300  
               
               
                   
               
               
                 act aca att tca ttt gaa aga ata aat gat gtt ctt gag cat gtc aaa     7082  
               
               
                 Thr Thr Ile Ser Phe Glu Arg Ile Asn Asp Val Leu Glu His Val Lys  
               
               
                         2305                2310                2315  
               
               
                   
               
               
                 cac ttt gtt ata aat ctt att ggg gat ttt gaa gta gct gag aaa atc     7130  
               
               
                 His Phe Val Ile Asn Leu Ile Gly Asp Phe Glu Val Ala Glu Lys Ile  
               
               
                     2320                2325                2330  
               
               
                   
               
               
                 aat gcc ttc aga gcc aaa gtc cat gag tta atc gag agg tat gaa gta     7178  
               
               
                 Asn Ala Phe Arg Ala Lys Val His Glu Leu Ile Glu Arg Tyr Glu Val  
               
               
                 2335                2340                2345                2350  
               
               
                   
               
               
                 gac caa caa atc cag gtt tta atg gat aaa tta gta gag ttg acc cac     7226  
               
               
                 Asp Gln Gln Ile Gln Val Leu Met Asp Lys Leu Val Glu Leu Thr His  
               
               
                                 2355                2360                2365  
               
               
                   
               
               
                 caa tac aag ttg aag gag act att cag aag cta agc aat gtc cta caa     7274  
               
               
                 Gln Tyr Lys Leu Lys Glu Thr Ile Gln Lys Leu Ser Asn Val Leu Gln  
               
               
                             2370                2375                2380  
               
               
                   
               
               
                 caa gtt aag ata aaa gat tac ttt gag aaa ttg gtt gga ttt att gat     7322  
               
               
                 Gln Val Lys Ile Lys Asp Tyr Phe Glu Lys Leu Val Gly Phe Ile Asp  
               
               
                         2385                2390                2395  
               
               
                   
               
               
                 gat gct gtg aag aag ctt aat gaa tta tct ttt aaa aca ttc att gaa     7370  
               
               
                 Asp Ala Val Lys Lys Leu Asn Glu Leu Ser Phe Lys Thr Phe Ile Glu  
               
               
                     2400                2405                2410  
               
               
                   
               
               
                 gat gtt aac aaa ttc ctt gac atg ttg ata aag aaa tta aag tca ttt     7418  
               
               
                 Asp Val Asn Lys Phe Leu Asp Met Leu Ile Lys Lys Leu Lys Ser Phe  
               
               
                 2415                2420                2425                2430  
               
               
                   
               
               
                 gat tac cac cag ttt gta gat gaa acc aat gac aaa atc cgt gag gtg     7466  
               
               
                 Asp Tyr His Gln Phe Val Asp Glu Thr Asn Asp Lys Ile Arg Glu Val  
               
               
                                 2435                2440                2445  
               
               
                   
               
               
                 act cag aga ctc aat ggt gaa att cag gct ctg gaa cta cca caa aaa     7514  
               
               
                 Thr Gln Arg Leu Asn Gly Glu Ile Gln Ala Leu Glu Leu Pro Gln Lys  
               
               
                             2450                2455                2460  
               
               
                   
               
               
                 gct gaa gca tta aaa ctg ttt tta gag gaa acc aag gcc aca gtt gca     7562  
               
               
                 Ala Glu Ala Leu Lys Leu Phe Leu Glu Glu Thr Lys Ala Thr Val Ala  
               
               
                         2465                2470                2475  
               
               
                   
               
               
                 gtg tat ctg gaa agc cta cag gac acc aaa ata acc tta atc atc aat     7610  
               
               
                 Val Tyr Leu Glu Ser Leu Gln Asp Thr Lys Ile Thr Leu Ile Ile Asn  
               
               
                     2480                2485                2490  
               
               
                   
               
               
                 tgg tta cag gag gct tta agt tca gca tct ttg gct cac atg aag gcc     7658  
               
               
                 Trp Leu Gln Glu Ala Leu Ser Ser Ala Ser Leu Ala His Met Lys Ala  
               
               
                 2495                2500                2505                2510  
               
               
                   
               
               
                 aaa ttc cga gag act cta gaa gat aca cga gac cga atg tat caa atg     7706  
               
               
                 Lys Phe Arg Glu Thr Leu Glu Asp Thr Arg Asp Arg Met Tyr Gln Met  
               
               
                                 2515                2520                2525  
               
               
                   
               
               
                 gac att cag cag gaa ctt caa cga tac ctg tct ctg gta ggc cag gtt     7754  
               
               
                 Asp Ile Gln Gln Glu Leu Gln Arg Tyr Leu Ser Leu Val Gly Gln Val  
               
               
                             2530                2535                2540  
               
               
                   
               
               
                 tat agc aca ctt gtc acc tac att tct gat tgg tgg act ctt gct gct     7802  
               
               
                 Tyr Ser Thr Leu Val Thr Tyr Ile Ser Asp Trp Trp Thr Leu Ala Ala  
               
               
                         2545                2550                2555  
               
               
                   
               
               
                 aag aac ctt act gac ttt gca gag caa tat tct atc caa gat tgg gct     7850  
               
               
                 Lys Asn Leu Thr Asp Phe Ala Glu Gln Tyr Ser Ile Gln Asp Trp Ala  
               
               
                     2560                2565                2570  
               
               
                   
               
               
                 aaa cgt atg aaa gca ttg gta gag caa ggg ttc act gtt cct gaa atc     7898  
               
               
                 Lys Arg Met Lys Ala Leu Val Glu Gln Gly Phe Thr Val Pro Glu Ile  
               
               
                 2575                2580                2585                2590  
               
               
                   
               
               
                 aag acc atc ctt ggg acc atg cct gcc ttt gaa gtc agt ctt cag gct     7946  
               
               
                 Lys Thr Ile Leu Gly Thr Met Pro Ala Phe Glu Val Ser Leu Gln Ala  
               
               
                                 2595                2600                2605  
               
               
                   
               
               
                 ctt cag aaa gct acc ttc cag aca cct gat ttt ata gtc ccc cta aca     7994  
               
               
                 Leu Gln Lys Ala Thr Phe Gln Thr Pro Asp Phe Ile Val Pro Leu Thr  
               
               
                             2610                2615                2620  
               
               
                   
               
               
                 gat ttg agg att cca tca gtt cag ata aac ttc aaa gac tta aaa aat     8042  
               
               
                 Asp Leu Arg Ile Pro Ser Val Gln Ile Asn Phe Lys Asp Leu Lys Asn  
               
               
                         2625                2630                2635  
               
               
                   
               
               
                 ata aaa atc cca tcc agg ttt tcc aca cca gaa ttt acc atc ctt aac     8090  
               
               
                 Ile Lys Ile Pro Ser Arg Phe Ser Thr Pro Glu Phe Thr Ile Leu Asn  
               
               
                     2640                2645                2650  
               
               
                   
               
               
                 acc ttc cac att cct tcc ttt aca att gac ttt gtc gaa atg aaa gta     8138  
               
               
                 Thr Phe His Ile Pro Ser Phe Thr Ile Asp Phe Val Glu Met Lys Val  
               
               
                 2655                2660                2665                2670  
               
               
                   
               
               
                 aag atc atc aga acc att gac cag atg cag aac agt gag ctg cag tgg     8186  
               
               
                 Lys Ile Ile Arg Thr Ile Asp Gln Met Gln Asn Ser Glu Leu Gln Trp  
               
               
                                 2675                2680                2685  
               
               
                   
               
               
                 ccc gtt cca gat ata tat ctc agg gat ctg aag gtg gag gac att cct     8234  
               
               
                 Pro Val Pro Asp Ile Tyr Leu Arg Asp Leu Lys Val Glu Asp Ile Pro  
               
               
                             2690                2695                2700  
               
               
                   
               
               
                 cta gcg aga atc acc ctg cca gac ttc cgt tta cca gaa atc gca att     8282  
               
               
                 Leu Ala Arg Ile Thr Leu Pro Asp Phe Arg Leu Pro Glu Ile Ala Ile  
               
               
                         2705                2710                2715  
               
               
                   
               
               
                 cca gaa ttc ata atc cca act ctc aac ctt aat gat ttt caa gtt cct     8330  
               
               
                 Pro Glu Phe Ile Ile Pro Thr Leu Asn Leu Asn Asp Phe Gln Val Pro  
               
               
                     2720                2725                2730  
               
               
                   
               
               
                 gac ctt cac ata cca gaa ttc cag ctt ccc cac atc tca cac aca att     8378  
               
               
                 Asp Leu His Ile Pro Glu Phe Gln Leu Pro His Ile Ser His Thr Ile  
               
               
                 2735                2740                2745                2750  
               
               
                   
               
               
                 gaa gta cct act ttt ggc aag cta tac agt att ctg aaa atc caa tct     8426  
               
               
                 Glu Val Pro Thr Phe Gly Lys Leu Tyr Ser Ile Leu Lys Ile Gln Ser  
               
               
                                 2755                2760                2765  
               
               
                   
               
               
                 cct ctt ttc aca tta gat gca aat gct gac ata ggg aat gga acc acc     8474  
               
               
                 Pro Leu Phe Thr Leu Asp Ala Asn Ala Asp Ile Gly Asn Gly Thr Thr  
               
               
                             2770                2775                2780  
               
               
                   
               
               
                 tca gca aac gaa gca ggt atc gca gct tcc atc act gcc aaa gga gag     8522  
               
               
                 Ser Ala Asn Glu Ala Gly Ile Ala Ala Ser Ile Thr Ala Lys Gly Glu  
               
               
                         2785                2790                2795  
               
               
                   
               
               
                 tcc aaa tta gaa gtt ctc aat ttt gat ttt caa gca aat gca caa ctc     8570  
               
               
                 Ser Lys Leu Glu Val Leu Asn Phe Asp Phe Gln Ala Asn Ala Gln Leu  
               
               
                     2800                2805                2810  
               
               
                   
               
               
                 tca aac cct aag att aat ccg ctg gct ctg aag gag tca gtg aag ttc     8618  
               
               
                 Ser Asn Pro Lys Ile Asn Pro Leu Ala Leu Lys Glu Ser Val Lys Phe  
               
               
                 2815                2820                2825                2830  
               
               
                   
               
               
                 tcc agc aag tac ctg aga acg gag cat ggg agt gaa atg ctg ttt ttt     8666  
               
               
                 Ser Ser Lys Tyr Leu Arg Thr Glu His Gly Ser Glu Met Leu Phe Phe  
               
               
                                 2835                2840                2845  
               
               
                   
               
               
                 gga aat gct att gag gga aaa tca aac aca gtg gca agt tta cac aca     8714  
               
               
                 Gly Asn Ala Ile Glu Gly Lys Ser Asn Thr Val Ala Ser Leu His Thr  
               
               
                             2850                2855                2860  
               
               
                   
               
               
                 gaa aaa aat aca ctg gag ctt agt aat gga gtg att gtc aag ata aac     8762  
               
               
                 Glu Lys Asn Thr Leu Glu Leu Ser Asn Gly Val Ile Val Lys Ile Asn  
               
               
                         2865                2870                2875  
               
               
                   
               
               
                 aat cag ctt acc ctg gat agc aac act aaa tac ttc cac aaa ttg aac     8810  
               
               
                 Asn Gln Leu Thr Leu Asp Ser Asn Thr Lys Tyr Phe His Lys Leu Asn  
               
               
                     2880                2885                2890  
               
               
                   
               
               
                 atc ccc aaa ctg gac ttc tct agt cag gct gac ctg cgc aac gag atc     8858  
               
               
                 Ile Pro Lys Leu Asp Phe Ser Ser Gln Ala Asp Leu Arg Asn Glu Ile  
               
               
                 2895                2900                2905                2910  
               
               
                   
               
               
                 aag aca ctg ttg aaa gct ggc cac ata gca tgg act tct tct gga aaa     8906  
               
               
                 Lys Thr Leu Leu Lys Ala Gly His Ile Ala Trp Thr Ser Ser Gly Lys  
               
               
                                 2915                2920                2925  
               
               
                   
               
               
                 ggg tca tgg aaa tgg gcc tgc ccc aga ttc tca gat gag gga aca cat     8954  
               
               
                 Gly Ser Trp Lys Trp Ala Cys Pro Arg Phe Ser Asp Glu Gly Thr His  
               
               
                             2930                2935                2940  
               
               
                   
               
               
                 gaa tca caa att agt ttc acc ata gaa gga ccc ctc act tcc ttt gga     9002  
               
               
                 Glu Ser Gln Ile Ser Phe Thr Ile Glu Gly Pro Leu Thr Ser Phe Gly  
               
               
                         2945                2950                2955  
               
               
                   
               
               
                 ctg tcc aat aag atc aat agc aaa cac cta aga gta aac caa aac ttg     9050  
               
               
                 Leu Ser Asn Lys Ile Asn Ser Lys His Leu Arg Val Asn Gln Asn Leu  
               
               
                     2960                2965                2970  
               
               
                   
               
               
                 gtt tat gaa tct ggc tcc ctc aac ttt tct aaa ctt gaa att caa tca     9098  
               
               
                 Val Tyr Glu Ser Gly Ser Leu Asn Phe Ser Lys Leu Glu Ile Gln Ser  
               
               
                 2975                2980                2985                2990  
               
               
                   
               
               
                 caa gtc gat tcc cag cat gtg ggc cac agt gtt cta act gct aaa ggc     9146  
               
               
                 Gln Val Asp Ser Gln His Val Gly His Ser Val Leu Thr Ala Lys Gly  
               
               
                                 2995                3000                3005  
               
               
                   
               
               
                 atg gca ctg ttt gga gaa ggg aag gca gag ttt act ggg agg cat gat     9194  
               
               
                 Met Ala Leu Phe Gly Glu Gly Lys Ala Glu Phe Thr Gly Arg His Asp  
               
               
                             3010                3015                3020  
               
               
                   
               
               
                 gct cat tta aat gga aag gtt att gga act ttg aaa aat tct ctt ttc     9242  
               
               
                 Ala His Leu Asn Gly Lys Val Ile Gly Thr Leu Lys Asn Ser Leu Phe  
               
               
                         3025                3030                3035  
               
               
                   
               
               
                 ttt tca gcc cag cca ttt gag atc acg gca tcc aca aac aat gaa ggg     9290  
               
               
                 Phe Ser Ala Gln Pro Phe Glu Ile Thr Ala Ser Thr Asn Asn Glu Gly  
               
               
                     3040                3045                3050  
               
               
                   
               
               
                 aat ttg aaa gtt cgt ttt cca tta agg tta aca ggg aag ata gac ttc     9338  
               
               
                 Asn Leu Lys Val Arg Phe Pro Leu Arg Leu Thr Gly Lys Ile Asp Phe  
               
               
                 3055                3060                3065                3070  
               
               
                   
               
               
                 ctg aat aac tat gca ctg ttt ctg agt ccc agt gcc cag caa gca agt     9386  
               
               
                 Leu Asn Asn Tyr Ala Leu Phe Leu Ser Pro Ser Ala Gln Gln Ala Ser  
               
               
                                 3075                3080                3085  
               
               
                   
               
               
                 tgg caa gta agt gct agg ttc aat cag tat aag tac aac caa aat ttc     9434  
               
               
                 Trp Gln Val Ser Ala Arg Phe Asn Gln Tyr Lys Tyr Asn Gln Asn Phe  
               
               
                             3090                3095                3100  
               
               
                   
               
               
                 tct gct gga aac aac gag aac att atg gag gcc cat gta gga ata aat     9482  
               
               
                 Ser Ala Gly Asn Asn Glu Asn Ile Met Glu Ala His Val Gly Ile Asn  
               
               
                         3105                3110                3115  
               
               
                   
               
               
                 gga gaa gca aat ctg gat ttc tta aac att cct tta aca att cct gaa     9530  
               
               
                 Gly Glu Ala Asn Leu Asp Phe Leu Asn Ile Pro Leu Thr Ile Pro Glu  
               
               
                     3120                3125                3130  
               
               
                   
               
               
                 atg cgt cta cct tac aca ata atc aca act cct cca ctg aaa gat ttc     9578  
               
               
                 Met Arg Leu Pro Tyr Thr Ile Ile Thr Thr Pro Pro Leu Lys Asp Phe  
               
               
                 3135                3140                3145                3150  
               
               
                   
               
               
                 tct cta tgg gaa aaa aca ggc ttg aag gaa ttc ttg aaa acg aca aag     9626  
               
               
                 Ser Leu Trp Glu Lys Thr Gly Leu Lys Glu Phe Leu Lys Thr Thr Lys  
               
               
                                 3155                3160                3165  
               
               
                   
               
               
                 caa tca ttt gat tta agt gta aaa gct cag tat aag aaa aac aaa cac     9674  
               
               
                 Gln Ser Phe Asp Leu Ser Val Lys Ala Gln Tyr Lys Lys Asn Lys His  
               
               
                             3170                3175                3180  
               
               
                   
               
               
                 agg cat tcc atc aca aat cct ttg gct gtg ctt tgt gag ttt atc agt     9722  
               
               
                 Arg His Ser Ile Thr Asn Pro Leu Ala Val Leu Cys Glu Phe Ile Ser  
               
               
                         3185                3190                3195  
               
               
                   
               
               
                 cag agc atc aaa tcc ttt gac agg cat ttt gaa aaa aac aga aac aat     9770  
               
               
                 Gln Ser Ile Lys Ser Phe Asp Arg His Phe Glu Lys Asn Arg Asn Asn  
               
               
                     3200                3205                3210  
               
               
                   
               
               
                 gca tta gat ttt gtc acc aaa tcc tat aat gaa aca aaa att aag ttt     9818  
               
               
                 Ala Leu Asp Phe Val Thr Lys Ser Tyr Asn Glu Thr Lys Ile Lys Phe  
               
               
                 3215                3220                3225                3230  
               
               
                   
               
               
                 gat aag tac aaa gct gaa aaa tct cac gac gag ctc ccc agg acc ttt     9866  
               
               
                 Asp Lys Tyr Lys Ala Glu Lys Ser His Asp Glu Leu Pro Arg Thr Phe  
               
               
                                 3235                3240                3245  
               
               
                   
               
               
                 caa att cct gga tac act gtt cca gtt gtc aat gtt gaa gtg tct cca     9914  
               
               
                 Gln Ile Pro Gly Tyr Thr Val Pro Val Val Asn Val Glu Val Ser Pro  
               
               
                             3250                3255                3260  
               
               
                   
               
               
                 ttc acc ata gag atg tcg gca ttc ggc tat gtg ttc cca aaa gca gtc     9962  
               
               
                 Phe Thr Ile Glu Met Ser Ala Phe Gly Tyr Val Phe Pro Lys Ala Val  
               
               
                         3265                3270                3275  
               
               
                   
               
               
                 agc atg cct agt ttc tcc atc cta ggt tct gac gtc cgt gtg cct tca    10010  
               
               
                 Ser Met Pro Ser Phe Ser Ile Leu Gly Ser Asp Val Arg Val Pro Ser  
               
               
                     3280                3285                3290  
               
               
                   
               
               
                 tac aca tta atc ctg cca tca tta gag ctg cca gtc ctt cat gtc cct    10058  
               
               
                 Tyr Thr Leu Ile Leu Pro Ser Leu Glu Leu Pro Val Leu His Val Pro  
               
               
                 3295                3300                3305                3310  
               
               
                   
               
               
                 aga aat ctc aag ctt tct ctt cca cat ttc aag gaa ttg tgt acc ata    10106  
               
               
                 Arg Asn Leu Lys Leu Ser Leu Pro His Phe Lys Glu Leu Cys Thr Ile  
               
               
                                 3315                3320                3325  
               
               
                   
               
               
                 agc cat att ttt att cct gcc atg ggc aat att acc tat gat ttc tcc    10154  
               
               
                 Ser His Ile Phe Ile Pro Ala Met Gly Asn Ile Thr Tyr Asp Phe Ser  
               
               
                             3330                3335                3340  
               
               
                   
               
               
                 ttt aaa tca agt gtc atc aca ctg aat acc aat gct gaa ctt ttt aac    10202  
               
               
                 Phe Lys Ser Ser Val Ile Thr Leu Asn Thr Asn Ala Glu Leu Phe Asn  
               
               
                         3345                3350                3355  
               
               
                   
               
               
                 cag tca gat att gtt gct cat ctc ctt tct tca tct tca tct gtc att    10250  
               
               
                 Gln Ser Asp Ile Val Ala His Leu Leu Ser Ser Ser Ser Ser Val Ile  
               
               
                     3360                3365                3370  
               
               
                   
               
               
                 gat gca ctg cag tac aaa tta gag ggc acc aca aga ttg aca aga aaa    10298  
               
               
                 Asp Ala Leu Gln Tyr Lys Leu Glu Gly Thr Thr Arg Leu Thr Arg Lys  
               
               
                 3375                3380                3385                3390  
               
               
                   
               
               
                 agg gga ttg aag tta gcc aca gct ctg tct ctg agc aac aaa ttt gtg    10346  
               
               
                 Arg Gly Leu Lys Leu Ala Thr Ala Leu Ser Leu Ser Asn Lys Phe Val  
               
               
                                 3395                3400                3405  
               
               
                   
               
               
                 gag ggt agt cat aac agt act gtg agc tta acc acg aaa aat atg gaa    10394  
               
               
                 Glu Gly Ser His Asn Ser Thr Val Ser Leu Thr Thr Lys Asn Met Glu  
               
               
                             3410                3415                3420  
               
               
                   
               
               
                 gtg tca gtg gca aaa acc aca aaa gcc gaa att cca att ttg aga atg    10442  
               
               
                 Val Ser Val Ala Lys Thr Thr Lys Ala Glu Ile Pro Ile Leu Arg Met  
               
               
                         3425                3430                3435  
               
               
                   
               
               
                 aat ttc aag caa gaa ctt aat gga aat acc aag tca aaa cct act gtc    10490  
               
               
                 Asn Phe Lys Gln Glu Leu Asn Gly Asn Thr Lys Ser Lys Pro Thr Val  
               
               
                     3440                3445                3450  
               
               
                   
               
               
                 tct tcc tcc atg gaa ttt aag tat gat ttc aat tct tca atg ctg tac    10538  
               
               
                 Ser Ser Ser Met Glu Phe Lys Tyr Asp Phe Asn Ser Ser Met Leu Tyr  
               
               
                 3455                3460                3465                3470  
               
               
                   
               
               
                 tct acc gct aaa gga gca gtt gac cac aag ctt agc ttg gaa agc ctc    10586  
               
               
                 Ser Thr Ala Lys Gly Ala Val Asp His Lys Leu Ser Leu Glu Ser Leu  
               
               
                                 3475                3480                3485  
               
               
                   
               
               
                 acc tct tac ttt tcc att gag tca tct acc aaa gga gat gtc aag ggt    10634  
               
               
                 Thr Ser Tyr Phe Ser Ile Glu Ser Ser Thr Lys Gly Asp Val Lys Gly  
               
               
                             3490                3495                3500  
               
               
                   
               
               
                 tcg gtt ctt tct cgg gaa tat tca gga act att gct agt gag gcc aac    10682  
               
               
                 Ser Val Leu Ser Arg Glu Tyr Ser Gly Thr Ile Ala Ser Glu Ala Asn  
               
               
                         3505                3510                3515  
               
               
                   
               
               
                 act tac ttg aat tcc aag agc aca cgg tct tca gtg aag ctg cag ggc    10730  
               
               
                 Thr Tyr Leu Asn Ser Lys Ser Thr Arg Ser Ser Val Lys Leu Gln Gly  
               
               
                     3520                3525                3530  
               
               
                   
               
               
                 act tcc aaa att gat gat atc tgg aac ctt gaa gta aaa gaa aat ttt    10778  
               
               
                 Thr Ser Lys Ile Asp Asp Ile Trp Asn Leu Glu Val Lys Glu Asn Phe  
               
               
                 3535                3540                3545                3550  
               
               
                   
               
               
                 gct gga gaa gcc aca ctc caa cgc ata tat tcc ctc tgg gag cac agt    10826  
               
               
                 Ala Gly Glu Ala Thr Leu Gln Arg Ile Tyr Ser Leu Trp Glu His Ser  
               
               
                                 3555                3560                3565  
               
               
                   
               
               
                 acg aaa aac cac tta cag cta gag ggc ctc ttt ttc acc aac gga gaa    10874  
               
               
                 Thr Lys Asn His Leu Gln Leu Glu Gly Leu Phe Phe Thr Asn Gly Glu  
               
               
                             3570                3575                3580  
               
               
                   
               
               
                 cat aca agc aaa gcc acc ctg gaa ctc tct cca tgg caa atg tca gct    10922  
               
               
                 His Thr Ser Lys Ala Thr Leu Glu Leu Ser Pro Trp Gln Met Ser Ala  
               
               
                         3585                3590                3595  
               
               
                   
               
               
                 ctt gtt cag gtc cat gca agt cag ccc agt tcc ttc cat gat ttc cct    10970  
               
               
                 Leu Val Gln Val His Ala Ser Gln Pro Ser Ser Phe His Asp Phe Pro  
               
               
                     3600                3605                3610  
               
               
                   
               
               
                 gac ctt ggc cag gaa gtg gcc ctg aat gct aac act aag aac cag aag    11018  
               
               
                 Asp Leu Gly Gln Glu Val Ala Leu Asn Ala Asn Thr Lys Asn Gln Lys  
               
               
                 3615                3620                3625                3630  
               
               
                   
               
               
                 atc aga tgg aaa aat gaa gtc cgg att cat tct ggg tct ttc cag agc    11066  
               
               
                 Ile Arg Trp Lys Asn Glu Val Arg Ile His Ser Gly Ser Phe Gln Ser  
               
               
                                 3635                3640                3645  
               
               
                   
               
               
                 cag gtc gag ctt tcc aat gac caa gaa aag gca cac ctt gac att gca    11114  
               
               
                 Gln Val Glu Leu Ser Asn Asp Gln Glu Lys Ala His Leu Asp Ile Ala  
               
               
                             3650                3655                3660  
               
               
                   
               
               
                 gga tcc tta gaa gga cac cta agg ttc ctc aaa aat atc atc cta cca    11162  
               
               
                 Gly Ser Leu Glu Gly His Leu Arg Phe Leu Lys Asn Ile Ile Leu Pro  
               
               
                         3665                3670                3675  
               
               
                   
               
               
                 gtc tat gac aag agc tta tgg gat ttc cta aag ctg gat gta acc acc    11210  
               
               
                 Val Tyr Asp Lys Ser Leu Trp Asp Phe Leu Lys Leu Asp Val Thr Thr  
               
               
                     3680                3685                3690  
               
               
                   
               
               
                 agc att ggt agg aga cag cat ctt cgt gtt tca act gcc ttt gtg tac    11258  
               
               
                 Ser Ile Gly Arg Arg Gln His Leu Arg Val Ser Thr Ala Phe Val Tyr  
               
               
                 3695                3700                3705                3710  
               
               
                   
               
               
                 acc aaa aac ccc aat ggc tat tca ttc tcc atc cct gta aaa gtt ttg    11306  
               
               
                 Thr Lys Asn Pro Asn Gly Tyr Ser Phe Ser Ile Pro Val Lys Val Leu  
               
               
                                 3715                3720                3725  
               
               
                   
               
               
                 gct gat aaa ttc att act cct ggg ctg aaa cta aat gat cta aat tca    11354  
               
               
                 Ala Asp Lys Phe Ile Thr Pro Gly Leu Lys Leu Asn Asp Leu Asn Ser  
               
               
                             3730                3735                3740  
               
               
                   
               
               
                 gtt ctt gtc atg cct acg ttc cat gtc cca ttt aca gat ctt cag gtt    11402  
               
               
                 Val Leu Val Met Pro Thr Phe His Val Pro Phe Thr Asp Leu Gln Val  
               
               
                         3745                3750                3755  
               
               
                   
               
               
                 cca tcg tgc aaa ctt gac ttc aga gaa ata caa atc tat aag aag ctg    11450  
               
               
                 Pro Ser Cys Lys Leu Asp Phe Arg Glu Ile Gln Ile Tyr Lys Lys Leu  
               
               
                     3760                3765                3770  
               
               
                   
               
               
                 aga act tca tca ttt gcc ctc aac cta cca aca ctc ccc gag gta aaa    11498  
               
               
                 Arg Thr Ser Ser Phe Ala Leu Asn Leu Pro Thr Leu Pro Glu Val Lys  
               
               
                 3775                3780                3785                3790  
               
               
                   
               
               
                 ttc cct gaa gtt gat gtg tta aca aaa tat tct caa cca gaa gac tcc    11546  
               
               
                 Phe Pro Glu Val Asp Val Leu Thr Lys Tyr Ser Gln Pro Glu Asp Ser  
               
               
                                 3795                3800                3805  
               
               
                   
               
               
                 ttg att ccc ttt ttt gag ata acc gtg cct gaa tct cag tta act gtg    11594  
               
               
                 Leu Ile Pro Phe Phe Glu Ile Thr Val Pro Glu Ser Gln Leu Thr Val  
               
               
                             3810                3815                3820  
               
               
                   
               
               
                 tcc cag ttc acg ctt cca aaa agt gtt tca gat ggc att gct gct ttg    11642  
               
               
                 Ser Gln Phe Thr Leu Pro Lys Ser Val Ser Asp Gly Ile Ala Ala Leu  
               
               
                         3825                3830                3835  
               
               
                   
               
               
                 gat cta aat gca gta gcc aac aag atc gca gac ttt gag ttg ccc acc    11690  
               
               
                 Asp Leu Asn Ala Val Ala Asn Lys Ile Ala Asp Phe Glu Leu Pro Thr  
               
               
                     3840                3845                3850  
               
               
                   
               
               
                 atc atc gtg cct gag cag acc att gag att ccc tcc att aag ttc tct    11738  
               
               
                 Ile Ile Val Pro Glu Gln Thr Ile Glu Ile Pro Ser Ile Lys Phe Ser  
               
               
                 3855                3860                3865                3870  
               
               
                   
               
               
                 gta cct gct gga att gtc att cct tcc ttt caa gca ctg act gca cgc    11786  
               
               
                 Val Pro Ala Gly Ile Val Ile Pro Ser Phe Gln Ala Leu Thr Ala Arg  
               
               
                                 3875                3880                3885  
               
               
                   
               
               
                 ttt gag gta gac tct ccc gtg tat aat gcc act tgg agt gcc agt ttg    11834  
               
               
                 Phe Glu Val Asp Ser Pro Val Tyr Asn Ala Thr Trp Ser Ala Ser Leu  
               
               
                             3890                3895                3900  
               
               
                   
               
               
                 aaa aac aaa gca gat tat gtt gaa aca gtc ctg gat tcc aca tgc agc    11882  
               
               
                 Lys Asn Lys Ala Asp Tyr Val Glu Thr Val Leu Asp Ser Thr Cys Ser  
               
               
                         3905                3910                3915  
               
               
                   
               
               
                 tca acc gta cag ttc cta gaa tat gaa cta aat gtt ttg gga aca cac    11930  
               
               
                 Ser Thr Val Gln Phe Leu Glu Tyr Glu Leu Asn Val Leu Gly Thr His  
               
               
                     3920                3925                3930  
               
               
                   
               
               
                 aaa atc gaa gat ggt acg tta gcc tct aag act aaa gga aca ctt gca    11978  
               
               
                 Lys Ile Glu Asp Gly Thr Leu Ala Ser Lys Thr Lys Gly Thr Leu Ala  
               
               
                 3935                3940                3945                3950  
               
               
                   
               
               
                 cac cgt gac ttc agt gca gaa tat gaa gaa gat ggc aaa ttt gaa gga    12026  
               
               
                 His Arg Asp Phe Ser Ala Glu Tyr Glu Glu Asp Gly Lys Phe Glu Gly  
               
               
                                 3955                3960                3965  
               
               
                   
               
               
                 ctt cag gaa tgg gaa gga aaa gcg cac ctc aat atc aaa agc cca gcg    12074  
               
               
                 Leu Gln Glu Trp Glu Gly Lys Ala His Leu Asn Ile Lys Ser Pro Ala  
               
               
                             3970                3975                3980  
               
               
                   
               
               
                 ttc acc gat ctc cat ctg cgc tac cag aaa gac aag aaa ggc atc tcc    12122  
               
               
                 Phe Thr Asp Leu His Leu Arg Tyr Gln Lys Asp Lys Lys Gly Ile Ser  
               
               
                         3985                3990                3995  
               
               
                   
               
               
                 acc tca gca gcc tcc cca gcc gta ggc acc gtg ggc atg gat atg gat    12170  
               
               
                 Thr Ser Ala Ala Ser Pro Ala Val Gly Thr Val Gly Met Asp Met Asp  
               
               
                     4000                4005                4010  
               
               
                   
               
               
                 gaa gat gac gac ttt tct aaa tgg aac ttc tac tac agc cct cag tcc    12218  
               
               
                 Glu Asp Asp Asp Phe Ser Lys Trp Asn Phe Tyr Tyr Ser Pro Gln Ser  
               
               
                 4015                4020                4025                4030  
               
               
                   
               
               
                 tct cca gat aaa aaa ctc acc ata ttc aaa act gag ttg agg gtc cgg    12266  
               
               
                 Ser Pro Asp Lys Lys Leu Thr Ile Phe Lys Thr Glu Leu Arg Val Arg  
               
               
                                 4035                4040                4045  
               
               
                   
               
               
                 gaa tct gat gag gaa act cag atc aaa gtt aat tgg gaa gaa gag gca    12314  
               
               
                 Glu Ser Asp Glu Glu Thr Gln Ile Lys Val Asn Trp Glu Glu Glu Ala  
               
               
                             4050                4055                4060  
               
               
                   
               
               
                 gct tct ggc ttg cta acc tct ctg aaa gac aac gtg ccc aag gcc aca    12362  
               
               
                 Ala Ser Gly Leu Leu Thr Ser Leu Lys Asp Asn Val Pro Lys Ala Thr  
               
               
                         4065                4070                4075  
               
               
                   
               
               
                 ggg gtc ctt tat gat tat gtc aac aag tac cac tgg gaa cac aca ggg    12410  
               
               
                 Gly Val Leu Tyr Asp Tyr Val Asn Lys Tyr His Trp Glu His Thr Gly  
               
               
                     4080                4085                4090  
               
               
                   
               
               
                 ctc acc ctg aga gaa gtg tct tca aag ctg aga aga aat ctg cag aac    12458  
               
               
                 Leu Thr Leu Arg Glu Val Ser Ser Lys Leu Arg Arg Asn Leu Gln Asn  
               
               
                 4095                4100                4105                4110  
               
               
                   
               
               
                 aat gct gag tgg gtt tat caa ggg gcc att agg caa att gat gat atc    12506  
               
               
                 Asn Ala Glu Trp Val Tyr Gln Gly Ala Ile Arg Gln Ile Asp Asp Ile  
               
               
                                 4115                4120                4125  
               
               
                   
               
               
                 gac gtg agg ttc cag aaa gca gcc agt ggc acc act ggg acc tac caa    12554  
               
               
                 Asp Val Arg Phe Gln Lys Ala Ala Ser Gly Thr Thr Gly Thr Tyr Gln  
               
               
                             4130                4135                4140  
               
               
                   
               
               
                 gag tgg aag gac aag gcc cag aat ctg tac cag gaa ctg ttg act cag    12602  
               
               
                 Glu Trp Lys Asp Lys Ala Gln Asn Leu Tyr Gln Glu Leu Leu Thr Gln  
               
               
                         4145                4150                4155  
               
               
                   
               
               
                 gaa ggc caa gcc agt ttc cag gga ctc aag gat aac gtg ttt gat ggc    12650  
               
               
                 Glu Gly Gln Ala Ser Phe Gln Gly Leu Lys Asp Asn Val Phe Asp Gly  
               
               
                     4160                4165                4170  
               
               
                   
               
               
                 ttg gta cga gtt act caa aaa ttc cat atg aaa gtc aag cat ctg att    12698  
               
               
                 Leu Val Arg Val Thr Gln Lys Phe His Met Lys Val Lys His Leu Ile  
               
               
                 4175                4180                4185                4190  
               
               
                   
               
               
                 gac tca ctc att gat ttt ctg aac ttc ccc aga ttc cag ttt ccg ggg    12746  
               
               
                 Asp Ser Leu Ile Asp Phe Leu Asn Phe Pro Arg Phe Gln Phe Pro Gly  
               
               
                                 4195                4200                4205  
               
               
                   
               
               
                 aaa cct ggg ata tac act agg gag gaa ctt tgc act atg ttc ata agg    12794  
               
               
                 Lys Pro Gly Ile Tyr Thr Arg Glu Glu Leu Cys Thr Met Phe Ile Arg  
               
               
                             4210                4215                4220  
               
               
                   
               
               
                 gag gta ggg acg gta ctg tcc cag gta tat tcg aaa gtc cat aat ggt    12842  
               
               
                 Glu Val Gly Thr Val Leu Ser Gln Val Tyr Ser Lys Val His Asn Gly  
               
               
                         4225                4230                4235  
               
               
                   
               
               
                 tca gaa ata ctg ttt tcc tat ttc caa gac cta gtg att aca ctt cct    12890  
               
               
                 Ser Glu Ile Leu Phe Ser Tyr Phe Gln Asp Leu Val Ile Thr Leu Pro  
               
               
                     4240                4245                4250  
               
               
                   
               
               
                 ttc gag tta agg aaa cat aaa cta ata gat gta atc tcg atg tat agg    12938  
               
               
                 Phe Glu Leu Arg Lys His Lys Leu Ile Asp Val Ile Ser Met Tyr Arg  
               
               
                 4255                4260                4265                4270  
               
               
                   
               
               
                 gaa ctg ttg aaa gat tta tca aaa gaa gcc caa gag gta ttt aaa gcc    12986  
               
               
                 Glu Leu Leu Lys Asp Leu Ser Lys Glu Ala Gln Glu Val Phe Lys Ala  
               
               
                                 4275                4280                4285  
               
               
                   
               
               
                 att cag tct ctc aag acc aca gag gtg cta cgt aat ctt cag gac ctt    13034  
               
               
                 Ile Gln Ser Leu Lys Thr Thr Glu Val Leu Arg Asn Leu Gln Asp Leu  
               
               
                             4290                4295                4300  
               
               
                   
               
               
                 tta caa ttc att ttc caa cta ata gaa gat aac att aaa cag ctg aaa    13082  
               
               
                 Leu Gln Phe Ile Phe Gln Leu Ile Glu Asp Asn Ile Lys Gln Leu Lys  
               
               
                         4305                4310                4315  
               
               
                   
               
               
                 gag atg aaa ttt act tat ctt att aat tat atc caa gat gag atc aac    13130  
               
               
                 Glu Met Lys Phe Thr Tyr Leu Ile Asn Tyr Ile Gln Asp Glu Ile Asn  
               
               
                     4320                4325                4330  
               
               
                   
               
               
                 aca atc ttc aat gat tat atc cca tat gtt ttt aaa ttg ttg aaa gaa    13178  
               
               
                 Thr Ile Phe Asn Asp Tyr Ile Pro Tyr Val Phe Lys Leu Leu Lys Glu  
               
               
                 4335                4340                4345                4350  
               
               
                   
               
               
                 aac cta tgc ctt aat ctt cat aag ttc aat gaa ttt att caa aac gag    13226  
               
               
                 Asn Leu Cys Leu Asn Leu His Lys Phe Asn Glu Phe Ile Gln Asn Glu  
               
               
                                 4355                4360                4365  
               
               
                   
               
               
                 ctt cag gaa gct tct caa gag tta cag cag atc cat caa tac att atg    13274  
               
               
                 Leu Gln Glu Ala Ser Gln Glu Leu Gln Gln Ile His Gln Tyr Ile Met  
               
               
                             4370                4375                4380  
               
               
                   
               
               
                 gcc ctt cgt gaa gaa tat ttt gat cca agt ata gtt ggc tgg aca gtg    13322  
               
               
                 Ala Leu Arg Glu Glu Tyr Phe Asp Pro Ser Ile Val Gly Trp Thr Val  
               
               
                         4385                4390                4395  
               
               
                   
               
               
                 aaa tat tat gaa ctt gaa gaa aag ata gtc agt ctg atc aag aac ctg    13370  
               
               
                 Lys Tyr Tyr Glu Leu Glu Glu Lys Ile Val Ser Leu Ile Lys Asn Leu  
               
               
                     4400                4405                4410  
               
               
                   
               
               
                 tta gtt gct ctt aag gac ttc cat tct gaa tat att gtc agt gcc tct    13418  
               
               
                 Leu Val Ala Leu Lys Asp Phe His Ser Glu Tyr Ile Val Ser Ala Ser  
               
               
                 4415                4420                4425                4430  
               
               
                   
               
               
                 aac ttt act tcc caa ctc tca agt caa gtt gag caa ttt ctg cac aga    13466  
               
               
                 Asn Phe Thr Ser Gln Leu Ser Ser Gln Val Glu Gln Phe Leu His Arg  
               
               
                                 4435                4440                4445  
               
               
                   
               
               
                 aat att cag gaa tat ctt agc atc ctt acc gat cca gat gga aaa ggg    13514  
               
               
                 Asn Ile Gln Glu Tyr Leu Ser Ile Leu Thr Asp Pro Asp Gly Lys Gly  
               
               
                             4450                4455                4460  
               
               
                   
               
               
                 aaa gag aag att gca gag ctt tct gcc act gct cag gaa ata att aaa    13562  
               
               
                 Lys Glu Lys Ile Ala Glu Leu Ser Ala Thr Ala Gln Glu Ile Ile Lys  
               
               
                         4465                4470                4475  
               
               
                   
               
               
                 agc cag gcc att gcg acg aag aaa ata att tct gat tac cac cag cag    13610  
               
               
                 Ser Gln Ala Ile Ala Thr Lys Lys Ile Ile Ser Asp Tyr His Gln Gln  
               
               
                     4480                4485                4490  
               
               
                   
               
               
                 ttt aga tat aaa ctg caa gat ttt tca gac caa ctc tct gat tac tat    13658  
               
               
                 Phe Arg Tyr Lys Leu Gln Asp Phe Ser Asp Gln Leu Ser Asp Tyr Tyr  
               
               
                 4495                4500                4505                4510  
               
               
                   
               
               
                 gaa aaa ttt att gct gaa tcc aaa aga ttg att gac ctg tcc att caa    13706  
               
               
                 Glu Lys Phe Ile Ala Glu Ser Lys Arg Leu Ile Asp Leu Ser Ile Gln  
               
               
                                 4515                4520                4525  
               
               
                   
               
               
                 aac tac cac aca ttt ctg ata tac atc acg gag tta ctg aaa aag ctg    13754  
               
               
                 Asn Tyr His Thr Phe Leu Ile Tyr Ile Thr Glu Leu Leu Lys Lys Leu  
               
               
                             4530                4535                4540  
               
               
                   
               
               
                 caa tca acc aca gtc atg aac ccc tac atg aag ctt gct cca gga gaa    13802  
               
               
                 Gln Ser Thr Thr Val Met Asn Pro Tyr Met Lys Leu Ala Pro Gly Glu  
               
               
                         4545                4550                4555  
               
               
                   
               
               
                 ctt act atc atc ctc taa ttttttaaaa gaaatcttca tttattcttc           13850  
               
               
                 Leu Thr Ile Ile Leu  *  
               
               
                     4560  
               
               
                   
               
               
                 ttttccaatt gaactttcac atagcacaga aaaaattcaa actgcctata ttgataaaac  13910  
               
               
                   
               
               
                 catacagtga gccagccttg cagtaggcag tagactataa gcagaagcac atatgaactg  13970  
               
               
                   
               
               
                 gacctgcacc aaagctggca ccagggctcg gaaggtctct gaactcagaa ggatggcatt  14030  
               
               
                   
               
               
                 ttttgcaagt taaagaaaat caggatctga gttattttgc taaacttggg ggaggaggaa  14090  
               
               
                   
               
               
                 caaataaatg gagtctttat tgtgtatcat a                                 14121  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 32  
               
               
                 &lt;211&gt; LENGTH: 4563  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 32  
               
               
                   
               
               
                 Met Asp Pro Pro Arg Pro Ala Leu Leu Ala Leu Leu Ala Leu Pro Ala  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Leu Leu Leu Leu Leu Leu Ala Gly Ala Arg Ala Glu Glu Glu Met Leu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Glu Asn Val Ser Leu Val Cys Pro Lys Asp Ala Thr Arg Phe Lys His  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Leu Arg Lys Tyr Thr Tyr Asn Tyr Glu Ala Glu Ser Ser Ser Gly Val  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Pro Gly Thr Ala Asp Ser Arg Ser Ala Thr Arg Ile Asn Cys Lys Val  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Glu Leu Glu Val Pro Gln Leu Cys Ser Phe Ile Leu Lys Thr Ser Gln  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Cys Thr Leu Lys Glu Val Tyr Gly Phe Asn Pro Glu Gly Lys Ala Leu  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Leu Lys Lys Thr Lys Asn Ser Glu Glu Phe Ala Ala Ala Met Ser Arg  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Tyr Glu Leu Lys Leu Ala Ile Pro Glu Gly Lys Gln Val Phe Leu Tyr  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Pro Glu Lys Asp Glu Pro Thr Tyr Ile Leu Asn Ile Lys Arg Gly Ile  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ile Ser Ala Leu Leu Val Pro Pro Glu Thr Glu Glu Ala Lys Gln Val  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Leu Phe Leu Asp Thr Val Tyr Gly Asn Cys Ser Thr His Phe Thr Val  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Lys Thr Arg Lys Gly Asn Val Ala Thr Glu Ile Ser Thr Glu Arg Asp  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Leu Gly Gln Cys Asp Arg Phe Lys Pro Ile Arg Thr Gly Ile Ser Pro  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Leu Ala Leu Ile Lys Gly Met Thr Arg Pro Leu Ser Thr Leu Ile Ser  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ser Ser Gln Ser Cys Gln Tyr Thr Leu Asp Ala Lys Arg Lys His Val  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ala Glu Ala Ile Cys Lys Glu Gln His Leu Phe Leu Pro Phe Ser Tyr  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Asn Asn Lys Tyr Gly Met Val Ala Gln Val Thr Gln Thr Leu Lys Leu  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Glu Asp Thr Pro Lys Ile Asn Ser Arg Phe Phe Gly Glu Gly Thr Lys  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Lys Met Gly Leu Ala Phe Glu Ser Thr Lys Ser Thr Ser Pro Pro Lys  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Gln Ala Glu Ala Val Leu Lys Thr Leu Gln Glu Leu Lys Lys Leu Thr  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Ile Ser Glu Gln Asn Ile Gln Arg Ala Asn Leu Phe Asn Lys Leu Val  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Thr Glu Leu Arg Gly Leu Ser Asp Glu Ala Val Thr Ser Leu Leu Pro  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Gln Leu Ile Glu Val Ser Ser Pro Ile Thr Leu Gln Ala Leu Val Gln  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Cys Gly Gln Pro Gln Cys Ser Thr His Ile Leu Gln Trp Leu Lys Arg  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Val His Ala Asn Pro Leu Leu Ile Asp Val Val Thr Tyr Leu Val Ala  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Leu Ile Pro Glu Pro Ser Ala Gln Gln Leu Arg Glu Ile Phe Asn Met  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Ala Arg Asp Gln Arg Ser Arg Ala Thr Leu Tyr Ala Leu Ser His Ala  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Val Asn Asn Tyr His Lys Thr Asn Pro Thr Gly Thr Gln Glu Leu Leu  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Asp Ile Ala Asn Tyr Leu Met Glu Gln Ile Gln Asp Asp Cys Thr Gly  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Asp Glu Asp Tyr Thr Tyr Leu Ile Leu Arg Val Ile Gly Asn Met Gly  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Gln Thr Met Glu Gln Leu Thr Pro Glu Leu Lys Ser Ser Ile Leu Lys  
               
               
                             500                 505                 510  
               
               
                   
               
               
                 Cys Val Gln Ser Thr Lys Pro Ser Leu Met Ile Gln Lys Ala Ala Ile  
               
               
                         515                 520                 525  
               
               
                   
               
               
                 Gln Ala Leu Arg Lys Met Glu Pro Lys Asp Lys Asp Gln Glu Val Leu  
               
               
                     530                 535                 540  
               
               
                   
               
               
                 Leu Gln Thr Phe Leu Asp Asp Ala Ser Pro Gly Asp Lys Arg Leu Ala  
               
               
                 545                 550                 555                 560  
               
               
                   
               
               
                 Ala Tyr Leu Met Leu Met Arg Ser Pro Ser Gln Ala Asp Ile Asn Lys  
               
               
                                 565                 570                 575  
               
               
                   
               
               
                 Ile Val Gln Ile Leu Pro Trp Glu Gln Asn Glu Gln Val Lys Asn Phe  
               
               
                             580                 585                 590  
               
               
                   
               
               
                 Val Ala Ser His Ile Ala Asn Ile Leu Asn Ser Glu Glu Leu Asp Ile  
               
               
                         595                 600                 605  
               
               
                   
               
               
                 Gln Asp Leu Lys Lys Leu Val Lys Glu Ala Leu Lys Glu Ser Gln Leu  
               
               
                     610                 615                 620  
               
               
                   
               
               
                 Pro Thr Val Met Asp Phe Arg Lys Phe Ser Arg Asn Tyr Gln Leu Tyr  
               
               
                 625                 630                 635                 640  
               
               
                   
               
               
                 Lys Ser Val Ser Leu Pro Ser Leu Asp Pro Ala Ser Ala Lys Ile Glu  
               
               
                                 645                 650                 655  
               
               
                   
               
               
                 Gly Asn Leu Ile Phe Asp Pro Asn Asn Tyr Leu Pro Lys Glu Ser Met  
               
               
                             660                 665                 670  
               
               
                   
               
               
                 Leu Lys Thr Thr Leu Thr Ala Phe Gly Phe Ala Ser Ala Asp Leu Ile  
               
               
                         675                 680                 685  
               
               
                   
               
               
                 Glu Ile Gly Leu Glu Gly Lys Gly Phe Glu Pro Thr Leu Glu Ala Leu  
               
               
                     690                 695                 700  
               
               
                   
               
               
                 Phe Gly Lys Gln Gly Phe Phe Pro Asp Ser Val Asn Lys Ala Leu Tyr  
               
               
                 705                 710                 715                 720  
               
               
                   
               
               
                 Trp Val Asn Gly Gln Val Pro Asp Gly Val Ser Lys Val Leu Val Asp  
               
               
                                 725                 730                 735  
               
               
                   
               
               
                 His Phe Gly Tyr Thr Lys Asp Asp Lys His Glu Gln Asp Met Val Asn  
               
               
                             740                 745                 750  
               
               
                   
               
               
                 Gly Ile Met Leu Ser Val Glu Lys Leu Ile Lys Asp Leu Lys Ser Lys  
               
               
                         755                 760                 765  
               
               
                   
               
               
                 Glu Val Pro Glu Ala Arg Ala Tyr Leu Arg Ile Leu Gly Glu Glu Leu  
               
               
                     770                 775                 780  
               
               
                   
               
               
                 Gly Phe Ala Ser Leu His Asp Leu Gln Leu Leu Gly Lys Leu Leu Leu  
               
               
                 785                 790                 795                 800  
               
               
                   
               
               
                 Met Gly Ala Arg Thr Leu Gln Gly Ile Pro Gln Met Ile Gly Glu Val  
               
               
                                 805                 810                 815  
               
               
                   
               
               
                 Ile Arg Lys Gly Ser Lys Asn Asp Phe Phe Leu His Tyr Ile Phe Met  
               
               
                             820                 825                 830  
               
               
                   
               
               
                 Glu Asn Ala Phe Glu Leu Pro Thr Gly Ala Gly Leu Gln Leu Gln Ile  
               
               
                         835                 840                 845  
               
               
                   
               
               
                 Ser Ser Ser Gly Val Ile Ala Pro Gly Ala Lys Ala Gly Val Lys Leu  
               
               
                     850                 855                 860  
               
               
                   
               
               
                 Glu Val Ala Asn Met Gln Ala Glu Leu Val Ala Lys Pro Ser Val Ser  
               
               
                 865                 870                 875                 880  
               
               
                   
               
               
                 Val Glu Phe Val Thr Asn Met Gly Ile Ile Ile Pro Asp Phe Ala Arg  
               
               
                                 885                 890                 895  
               
               
                   
               
               
                 Ser Gly Val Gln Met Asn Thr Asn Phe Phe His Glu Ser Gly Leu Glu  
               
               
                             900                 905                 910  
               
               
                   
               
               
                 Ala His Val Ala Leu Lys Ala Gly Lys Leu Lys Phe Ile Ile Pro Ser  
               
               
                         915                 920                 925  
               
               
                   
               
               
                 Pro Lys Arg Pro Val Lys Leu Leu Ser Gly Gly Asn Thr Leu His Leu  
               
               
                     930                 935                 940  
               
               
                   
               
               
                 Val Ser Thr Thr Lys Thr Glu Val Ile Pro Pro Leu Ile Glu Asn Arg  
               
               
                 945                 950                 955                 960  
               
               
                   
               
               
                 Gln Ser Trp Ser Val Cys Lys Gln Val Phe Pro Gly Leu Asn Tyr Cys  
               
               
                                 965                 970                 975  
               
               
                   
               
               
                 Thr Ser Gly Ala Tyr Ser Asn Ala Ser Ser Thr Asp Ser Ala Ser Tyr  
               
               
                             980                 985                 990  
               
               
                   
               
               
                 Tyr Pro Leu Thr Gly Asp Thr Arg Leu Glu Leu Glu Leu Arg Pro Thr  
               
               
                         995                 1000                1005  
               
               
                   
               
               
                 Gly Glu Ile Glu Gln Tyr Ser Val Ser Ala Thr Tyr Glu Leu Gln Arg  
               
               
                     1010                1015                1020  
               
               
                   
               
               
                 Glu Asp Arg Ala Leu Val Asp Thr Leu Lys Phe Val Thr Gln Ala Glu  
               
               
                 1025                1030                1035                1040  
               
               
                   
               
               
                 Gly Ala Lys Gln Thr Glu Ala Thr Met Thr Phe Lys Tyr Asn Arg Gln  
               
               
                                 1045                1050                1055  
               
               
                   
               
               
                 Ser Met Thr Leu Ser Ser Glu Val Gln Ile Pro Asp Phe Asp Val Asp  
               
               
                             1060                1065                1070  
               
               
                   
               
               
                 Leu Gly Thr Ile Leu Arg Val Asn Asp Glu Ser Thr Glu Gly Lys Thr  
               
               
                         1075                1080                1085  
               
               
                   
               
               
                 Ser Tyr Arg Leu Thr Leu Asp Ile Gln Asn Lys Lys Ile Thr Glu Val  
               
               
                     1090                1095                1100  
               
               
                   
               
               
                 Ala Leu Met Gly His Leu Ser Cys Asp Thr Lys Glu Glu Arg Lys Ile  
               
               
                 1105                1110                1115                1120  
               
               
                   
               
               
                 Lys Gly Val Ile Ser Ile Pro Arg Leu Gln Ala Glu Ala Arg Ser Glu  
               
               
                                 1125                1130                1135  
               
               
                   
               
               
                 Ile Leu Ala His Trp Ser Pro Ala Lys Leu Leu Leu Gln Met Asp Ser  
               
               
                             1140                1145                1150  
               
               
                   
               
               
                 Ser Ala Thr Ala Tyr Gly Ser Thr Val Ser Lys Arg Val Ala Trp His  
               
               
                         1155                1160                1165  
               
               
                   
               
               
                 Tyr Asp Glu Glu Lys Ile Glu Phe Glu Trp Asn Thr Gly Thr Asn Val  
               
               
                     1170                1175                1180  
               
               
                   
               
               
                 Asp Thr Lys Lys Met Thr Ser Asn Phe Pro Val Asp Leu Ser Asp Tyr  
               
               
                 1185                1190                1195                1200  
               
               
                   
               
               
                 Pro Lys Ser Leu His Met Tyr Ala Asn Arg Leu Leu Asp His Arg Val  
               
               
                                 1205                1210                1215  
               
               
                   
               
               
                 Pro Glu Thr Asp Met Thr Phe Arg His Val Gly Ser Lys Leu Ile Val  
               
               
                             1220                1225                1230  
               
               
                   
               
               
                 Ala Met Ser Ser Trp Leu Gln Lys Ala Ser Gly Ser Leu Pro Tyr Thr  
               
               
                         1235                1240                1245  
               
               
                   
               
               
                 Gln Thr Leu Gln Asp His Leu Asn Ser Leu Lys Glu Phe Asn Leu Gln  
               
               
                     1250                1255                1260  
               
               
                   
               
               
                 Asn Met Gly Leu Pro Asp Phe His Ile Pro Glu Asn Leu Phe Leu Lys  
               
               
                 1265                1270                1275                1280  
               
               
                   
               
               
                 Ser Asp Gly Arg Val Lys Tyr Thr Leu Asn Lys Asn Ser Leu Lys Ile  
               
               
                                 1285                1290                1295  
               
               
                   
               
               
                 Glu Ile Pro Leu Pro Phe Gly Gly Lys Ser Ser Arg Asp Leu Lys Met  
               
               
                             1300                1305                1310  
               
               
                   
               
               
                 Leu Glu Thr Val Arg Thr Pro Ala Leu His Phe Lys Ser Val Gly Phe  
               
               
                         1315                1320                1325  
               
               
                   
               
               
                 His Leu Pro Ser Arg Glu Phe Gln Val Pro Thr Phe Thr Ile Pro Lys  
               
               
                     1330                1335                1340  
               
               
                   
               
               
                 Leu Tyr Gln Leu Gln Val Pro Leu Leu Gly Val Leu Asp Leu Ser Thr  
               
               
                 1345                1350                1355                1360  
               
               
                   
               
               
                 Asn Val Tyr Ser Asn Leu Tyr Asn Trp Ser Ala Ser Tyr Ser Gly Gly  
               
               
                                 1365                1370                1375  
               
               
                   
               
               
                 Asn Thr Ser Thr Asp His Phe Ser Leu Arg Ala Arg Tyr His Met Lys  
               
               
                             1380                1385                1390  
               
               
                   
               
               
                 Ala Asp Ser Val Val Asp Leu Leu Ser Tyr Asn Val Gln Gly Ser Gly  
               
               
                         1395                1400                1405  
               
               
                   
               
               
                 Glu Thr Thr Tyr Asp His Lys Asn Thr Phe Thr Leu Ser Cys Asp Gly  
               
               
                     1410                1415                1420  
               
               
                   
               
               
                 Ser Leu Arg His Lys Phe Leu Asp Ser Asn Ile Lys Phe Ser His Val  
               
               
                 1425                1430                1435                1440  
               
               
                   
               
               
                 Glu Lys Leu Gly Asn Asn Pro Val Ser Lys Gly Leu Leu Ile Phe Asp  
               
               
                                 1445                1450                1455  
               
               
                   
               
               
                 Ala Ser Ser Ser Trp Gly Pro Gln Met Ser Ala Ser Val His Leu Asp  
               
               
                             1460                1465                1470  
               
               
                   
               
               
                 Ser Lys Lys Lys Gln His Leu Phe Val Lys Glu Val Lys Ile Asp Gly  
               
               
                         1475                1480                1485  
               
               
                   
               
               
                 Gln Phe Arg Val Ser Ser Phe Tyr Ala Lys Gly Thr Tyr Gly Leu Ser  
               
               
                     1490                1495                1500  
               
               
                   
               
               
                 Cys Gln Arg Asp Pro Asn Thr Gly Arg Leu Asn Gly Glu Ser Asn Leu  
               
               
                 1505                1510                1515                1520  
               
               
                   
               
               
                 Arg Phe Asn Ser Ser Tyr Leu Gln Gly Thr Asn Gln Ile Thr Gly Arg  
               
               
                                 1525                1530                1535  
               
               
                   
               
               
                 Tyr Glu Asp Gly Thr Leu Ser Leu Thr Ser Thr Ser Asp Leu Gln Ser  
               
               
                             1540                1545                1550  
               
               
                   
               
               
                 Gly Ile Ile Lys Asn Thr Ala Ser Leu Lys Tyr Glu Asn Tyr Glu Leu  
               
               
                         1555                1560                1565  
               
               
                   
               
               
                 Thr Leu Lys Ser Asp Thr Asn Gly Lys Tyr Lys Asn Phe Ala Thr Ser  
               
               
                     1570                1575                1580  
               
               
                   
               
               
                 Asn Lys Met Asp Met Thr Phe Ser Lys Gln Asn Ala Leu Leu Arg Ser  
               
               
                 1585                1590                1595                1600  
               
               
                   
               
               
                 Glu Tyr Gln Ala Asp Tyr Glu Ser Leu Arg Phe Phe Ser Leu Leu Ser  
               
               
                                 1605                1610                1615  
               
               
                   
               
               
                 Gly Ser Leu Asn Ser His Gly Leu Glu Leu Asn Ala Asp Ile Leu Gly  
               
               
                             1620                1625                1630  
               
               
                   
               
               
                 Thr Asp Lys Ile Asn Ser Gly Ala His Lys Ala Thr Leu Arg Ile Gly  
               
               
                         1635                1640                1645  
               
               
                   
               
               
                 Gln Asp Gly Ile Ser Thr Ser Ala Thr Thr Asn Leu Lys Cys Ser Leu  
               
               
                     1650                1655                1660  
               
               
                   
               
               
                 Leu Val Leu Glu Asn Glu Leu Asn Ala Glu Leu Gly Leu Ser Gly Ala  
               
               
                 1665                1670                1675                1680  
               
               
                   
               
               
                 Ser Met Lys Leu Thr Thr Asn Gly Arg Phe Arg Glu His Asn Ala Lys  
               
               
                                 1685                1690                1695  
               
               
                   
               
               
                 Phe Ser Leu Asp Gly Lys Ala Ala Leu Thr Glu Leu Ser Leu Gly Ser  
               
               
                             1700                1705                1710  
               
               
                   
               
               
                 Ala Tyr Gln Ala Met Ile Leu Gly Val Asp Ser Lys Asn Ile Phe Asn  
               
               
                         1715                1720                1725  
               
               
                   
               
               
                 Phe Lys Val Ser Gln Glu Gly Leu Lys Leu Ser Asn Asp Met Met Gly  
               
               
                     1730                1735                1740  
               
               
                   
               
               
                 Ser Tyr Ala Glu Met Lys Phe Asp His Thr Asn Ser Leu Asn Ile Ala  
               
               
                 1745                1750                1755                1760  
               
               
                   
               
               
                 Gly Leu Ser Leu Asp Phe Ser Ser Lys Leu Asp Asn Ile Tyr Ser Ser  
               
               
                                 1765                1770                1775  
               
               
                   
               
               
                 Asp Lys Phe Tyr Lys Gln Thr Val Asn Leu Gln Leu Gln Pro Tyr Ser  
               
               
                             1780                1785                1790  
               
               
                   
               
               
                 Leu Val Thr Thr Leu Asn Ser Asp Leu Lys Tyr Asn Ala Leu Asp Leu  
               
               
                         1795                1800                1805  
               
               
                   
               
               
                 Thr Asn Asn Gly Lys Leu Arg Leu Glu Pro Leu Lys Leu His Val Ala  
               
               
                     1810                1815                1820  
               
               
                   
               
               
                 Gly Asn Leu Lys Gly Ala Tyr Gln Asn Asn Glu Ile Lys His Ile Tyr  
               
               
                 1825                1830                1835                1840  
               
               
                   
               
               
                 Ala Ile Ser Ser Ala Ala Leu Ser Ala Ser Tyr Lys Ala Asp Thr Val  
               
               
                                 1845                1850                1855  
               
               
                   
               
               
                 Ala Lys Val Gln Gly Val Glu Phe Ser His Arg Leu Asn Thr Asp Ile  
               
               
                             1860                1865                1870  
               
               
                   
               
               
                 Ala Gly Leu Ala Ser Ala Ile Asp Met Ser Thr Asn Tyr Asn Ser Asp  
               
               
                         1875                1880                1885  
               
               
                   
               
               
                 Ser Leu His Phe Ser Asn Val Phe Arg Ser Val Met Ala Pro Phe Thr  
               
               
                     1890                1895                1900  
               
               
                   
               
               
                 Met Thr Ile Asp Ala His Thr Asn Gly Asn Gly Lys Leu Ala Leu Trp  
               
               
                 1905                1910                1915                1920  
               
               
                   
               
               
                 Gly Glu His Thr Gly Gln Leu Tyr Ser Lys Phe Leu Leu Lys Ala Glu  
               
               
                                 1925                1930                1935  
               
               
                   
               
               
                 Pro Leu Ala Phe Thr Phe Ser His Asp Tyr Lys Gly Ser Thr Ser His  
               
               
                             1940                1945                1950  
               
               
                   
               
               
                 His Leu Val Ser Arg Lys Ser Ile Ser Ala Ala Leu Glu His Lys Val  
               
               
                         1955                1960                1965  
               
               
                   
               
               
                 Ser Ala Leu Leu Thr Pro Ala Glu Gln Thr Gly Thr Trp Lys Leu Lys  
               
               
                     1970                1975                1980  
               
               
                   
               
               
                 Thr Gln Phe Asn Asn Asn Glu Tyr Ser Gln Asp Leu Asp Ala Tyr Asn  
               
               
                 1985                1990                1995                2000  
               
               
                   
               
               
                 Thr Lys Asp Lys Ile Gly Val Glu Leu Thr Gly Arg Thr Leu Ala Asp  
               
               
                                 2005                2010                2015  
               
               
                   
               
               
                 Leu Thr Leu Leu Asp Ser Pro Ile Lys Val Pro Leu Leu Leu Ser Glu  
               
               
                             2020                2025                2030  
               
               
                   
               
               
                 Pro Ile Asn Ile Ile Asp Ala Leu Glu Met Arg Asp Ala Val Glu Lys  
               
               
                         2035                2040                2045  
               
               
                   
               
               
                 Pro Gln Glu Phe Thr Ile Val Ala Phe Val Lys Tyr Asp Lys Asn Gln  
               
               
                     2050                2055                2060  
               
               
                   
               
               
                 Asp Val His Ser Ile Asn Leu Pro Phe Phe Glu Thr Leu Gln Glu Tyr  
               
               
                 2065                2070                2075                2080  
               
               
                   
               
               
                 Phe Glu Arg Asn Arg Gln Thr Ile Ile Val Val Val Glu Asn Val Gln  
               
               
                                 2085                2090                2095  
               
               
                   
               
               
                 Arg Asn Leu Lys His Ile Asn Ile Asp Gln Phe Val Arg Lys Tyr Arg  
               
               
                             2100                2105                2110  
               
               
                   
               
               
                 Ala Ala Leu Gly Lys Leu Pro Gln Gln Ala Asn Asp Tyr Leu Asn Ser  
               
               
                         2115                2120                2125  
               
               
                   
               
               
                 Phe Asn Trp Glu Arg Gln Val Ser His Ala Lys Glu Lys Leu Thr Ala  
               
               
                     2130                2135                2140  
               
               
                   
               
               
                 Leu Thr Lys Lys Tyr Arg Ile Thr Glu Asn Asp Ile Gln Ile Ala Leu  
               
               
                 2145                2150                2155                2160  
               
               
                   
               
               
                 Asp Asp Ala Lys Ile Asn Phe Asn Glu Lys Leu Ser Gln Leu Gln Thr  
               
               
                                 2165                2170                2175  
               
               
                   
               
               
                 Tyr Met Ile Gln Phe Asp Gln Tyr Ile Lys Asp Ser Tyr Asp Leu His  
               
               
                             2180                2185                2190  
               
               
                   
               
               
                 Asp Leu Lys Ile Ala Ile Ala Asn Ile Ile Asp Glu Ile Ile Glu Lys  
               
               
                         2195                2200                2205  
               
               
                   
               
               
                 Leu Lys Ser Leu Asp Glu His Tyr His Ile Arg Val Asn Leu Val Lys  
               
               
                     2210                2215                2220  
               
               
                   
               
               
                 Thr Ile His Asp Leu His Leu Phe Ile Glu Asn Ile Asp Phe Asn Lys  
               
               
                 2225                2230                2235                2240  
               
               
                   
               
               
                 Ser Gly Ser Ser Thr Ala Ser Trp Ile Gln Asn Val Asp Thr Lys Tyr  
               
               
                                 2245                2250                2255  
               
               
                   
               
               
                 Gln Ile Arg Ile Gln Ile Gln Glu Lys Leu Gln Gln Leu Lys Arg His  
               
               
                             2260                2265                2270  
               
               
                   
               
               
                 Ile Gln Asn Ile Asp Ile Gln His Leu Ala Gly Lys Leu Lys Gln His  
               
               
                         2275                2280                2285  
               
               
                   
               
               
                 Ile Glu Ala Ile Asp Val Arg Val Leu Leu Asp Gln Leu Gly Thr Thr  
               
               
                     2290                2295                2300  
               
               
                   
               
               
                 Ile Ser Phe Glu Arg Ile Asn Asp Val Leu Glu His Val Lys His Phe  
               
               
                 2305                2310                2315                2320  
               
               
                   
               
               
                 Val Ile Asn Leu Ile Gly Asp Phe Glu Val Ala Glu Lys Ile Asn Ala  
               
               
                                 2325                2330                2335  
               
               
                   
               
               
                 Phe Arg Ala Lys Val His Glu Leu Ile Glu Arg Tyr Glu Val Asp Gln  
               
               
                             2340                2345                2350  
               
               
                   
               
               
                 Gln Ile Gln Val Leu Met Asp Lys Leu Val Glu Leu Thr His Gln Tyr  
               
               
                         2355                2360                2365  
               
               
                   
               
               
                 Lys Leu Lys Glu Thr Ile Gln Lys Leu Ser Asn Val Leu Gln Gln Val  
               
               
                     2370                2375                2380  
               
               
                   
               
               
                 Lys Ile Lys Asp Tyr Phe Glu Lys Leu Val Gly Phe Ile Asp Asp Ala  
               
               
                 2385                2390                2395                2400  
               
               
                   
               
               
                 Val Lys Lys Leu Asn Glu Leu Ser Phe Lys Thr Phe Ile Glu Asp Val  
               
               
                                 2405                2410                2415  
               
               
                   
               
               
                 Asn Lys Phe Leu Asp Met Leu Ile Lys Lys Leu Lys Ser Phe Asp Tyr  
               
               
                             2420                2425                2430  
               
               
                   
               
               
                 His Gln Phe Val Asp Glu Thr Asn Asp Lys Ile Arg Glu Val Thr Gln  
               
               
                         2435                2440                2445  
               
               
                   
               
               
                 Arg Leu Asn Gly Glu Ile Gln Ala Leu Glu Leu Pro Gln Lys Ala Glu  
               
               
                     2450                2455                2460  
               
               
                   
               
               
                 Ala Leu Lys Leu Phe Leu Glu Glu Thr Lys Ala Thr Val Ala Val Tyr  
               
               
                 2465                2470                2475                2480  
               
               
                   
               
               
                 Leu Glu Ser Leu Gln Asp Thr Lys Ile Thr Leu Ile Ile Asn Trp Leu  
               
               
                                 2485                2490                2495  
               
               
                   
               
               
                 Gln Glu Ala Leu Ser Ser Ala Ser Leu Ala His Met Lys Ala Lys Phe  
               
               
                             2500                2505                2510  
               
               
                   
               
               
                 Arg Glu Thr Leu Glu Asp Thr Arg Asp Arg Met Tyr Gln Met Asp Ile  
               
               
                         2515                2520                2525  
               
               
                   
               
               
                 Gln Gln Glu Leu Gln Arg Tyr Leu Ser Leu Val Gly Gln Val Tyr Ser  
               
               
                     2530                2535                2540  
               
               
                   
               
               
                 Thr Leu Val Thr Tyr Ile Ser Asp Trp Trp Thr Leu Ala Ala Lys Asn  
               
               
                 2545                2550                2555                2560  
               
               
                   
               
               
                 Leu Thr Asp Phe Ala Glu Gln Tyr Ser Ile Gln Asp Trp Ala Lys Arg  
               
               
                                 2565                2570                2575  
               
               
                   
               
               
                 Met Lys Ala Leu Val Glu Gln Gly Phe Thr Val Pro Glu Ile Lys Thr  
               
               
                             2580                2585                2590  
               
               
                   
               
               
                 Ile Leu Gly Thr Met Pro Ala Phe Glu Val Ser Leu Gln Ala Leu Gln  
               
               
                         2595                2600                2605  
               
               
                   
               
               
                 Lys Ala Thr Phe Gln Thr Pro Asp Phe Ile Val Pro Leu Thr Asp Leu  
               
               
                     2610                2615                2620  
               
               
                   
               
               
                 Arg Ile Pro Ser Val Gln Ile Asn Phe Lys Asp Leu Lys Asn Ile Lys  
               
               
                 2625                2630                2635                2640  
               
               
                   
               
               
                 Ile Pro Ser Arg Phe Ser Thr Pro Glu Phe Thr Ile Leu Asn Thr Phe  
               
               
                                 2645                2650                2655  
               
               
                   
               
               
                 His Ile Pro Ser Phe Thr Ile Asp Phe Val Glu Met Lys Val Lys Ile  
               
               
                             2660                2665                2670  
               
               
                   
               
               
                 Ile Arg Thr Ile Asp Gln Met Gln Asn Ser Glu Leu Gln Trp Pro Val  
               
               
                         2675                2680                2685  
               
               
                   
               
               
                 Pro Asp Ile Tyr Leu Arg Asp Leu Lys Val Glu Asp Ile Pro Leu Ala  
               
               
                     2690                2695                2700  
               
               
                   
               
               
                 Arg Ile Thr Leu Pro Asp Phe Arg Leu Pro Glu Ile Ala Ile Pro Glu  
               
               
                 2705                2710                2715                2720  
               
               
                   
               
               
                 Phe Ile Ile Pro Thr Leu Asn Leu Asn Asp Phe Gln Val Pro Asp Leu  
               
               
                                 2725                2730                2735  
               
               
                   
               
               
                 His Ile Pro Glu Phe Gln Leu Pro His Ile Ser His Thr Ile Glu Val  
               
               
                             2740                2745                2750  
               
               
                   
               
               
                 Pro Thr Phe Gly Lys Leu Tyr Ser Ile Leu Lys Ile Gln Ser Pro Leu  
               
               
                         2755                2760                2765  
               
               
                   
               
               
                 Phe Thr Leu Asp Ala Asn Ala Asp Ile Gly Asn Gly Thr Thr Ser Ala  
               
               
                     2770                2775                2780  
               
               
                   
               
               
                 Asn Glu Ala Gly Ile Ala Ala Ser Ile Thr Ala Lys Gly Glu Ser Lys  
               
               
                 2785                2790                2795                2800  
               
               
                   
               
               
                 Leu Glu Val Leu Asn Phe Asp Phe Gln Ala Asn Ala Gln Leu Ser Asn  
               
               
                                 2805                2810                2815  
               
               
                   
               
               
                 Pro Lys Ile Asn Pro Leu Ala Leu Lys Glu Ser Val Lys Phe Ser Ser  
               
               
                             2820                2825                2830  
               
               
                   
               
               
                 Lys Tyr Leu Arg Thr Glu His Gly Ser Glu Met Leu Phe Phe Gly Asn  
               
               
                         2835                2840                2845  
               
               
                   
               
               
                 Ala Ile Glu Gly Lys Ser Asn Thr Val Ala Ser Leu His Thr Glu Lys  
               
               
                     2850                2855                2860  
               
               
                   
               
               
                 Asn Thr Leu Glu Leu Ser Asn Gly Val Ile Val Lys Ile Asn Asn Gln  
               
               
                 2865                2870                2875                2880  
               
               
                   
               
               
                 Leu Thr Leu Asp Ser Asn Thr Lys Tyr Phe His Lys Leu Asn Ile Pro  
               
               
                                 2885                2890                2895  
               
               
                   
               
               
                 Lys Leu Asp Phe Ser Ser Gln Ala Asp Leu Arg Asn Glu Ile Lys Thr  
               
               
                             2900                2905                2910  
               
               
                   
               
               
                 Leu Leu Lys Ala Gly His Ile Ala Trp Thr Ser Ser Gly Lys Gly Ser  
               
               
                         2915                2920                2925  
               
               
                   
               
               
                 Trp Lys Trp Ala Cys Pro Arg Phe Ser Asp Glu Gly Thr His Glu Ser  
               
               
                     2930                2935                2940  
               
               
                   
               
               
                 Gln Ile Ser Phe Thr Ile Glu Gly Pro Leu Thr Ser Phe Gly Leu Ser  
               
               
                 2945                2950                2955                2960  
               
               
                   
               
               
                 Asn Lys Ile Asn Ser Lys His Leu Arg Val Asn Gln Asn Leu Val Tyr  
               
               
                                 2965                2970                2975  
               
               
                   
               
               
                 Glu Ser Gly Ser Leu Asn Phe Ser Lys Leu Glu Ile Gln Ser Gln Val  
               
               
                             2980                2985                2990  
               
               
                   
               
               
                 Asp Ser Gln His Val Gly His Ser Val Leu Thr Ala Lys Gly Met Ala  
               
               
                         2995                3000                3005  
               
               
                   
               
               
                 Leu Phe Gly Glu Gly Lys Ala Glu Phe Thr Gly Arg His Asp Ala His  
               
               
                     3010                3015                3020  
               
               
                   
               
               
                 Leu Asn Gly Lys Val Ile Gly Thr Leu Lys Asn Ser Leu Phe Phe Ser  
               
               
                 3025                3030                3035                3040  
               
               
                   
               
               
                 Ala Gln Pro Phe Glu Ile Thr Ala Ser Thr Asn Asn Glu Gly Asn Leu  
               
               
                                 3045                3050                3055  
               
               
                   
               
               
                 Lys Val Arg Phe Pro Leu Arg Leu Thr Gly Lys Ile Asp Phe Leu Asn  
               
               
                             3060                3065                3070  
               
               
                   
               
               
                 Asn Tyr Ala Leu Phe Leu Ser Pro Ser Ala Gln Gln Ala Ser Trp Gln  
               
               
                         3075                3080                3085  
               
               
                   
               
               
                 Val Ser Ala Arg Phe Asn Gln Tyr Lys Tyr Asn Gln Asn Phe Ser Ala  
               
               
                     3090                3095                3100  
               
               
                   
               
               
                 Gly Asn Asn Glu Asn Ile Met Glu Ala His Val Gly Ile Asn Gly Glu  
               
               
                 3105                3110                3115                3120  
               
               
                   
               
               
                 Ala Asn Leu Asp Phe Leu Asn Ile Pro Leu Thr Ile Pro Glu Met Arg  
               
               
                                 3125                3130                3135  
               
               
                   
               
               
                 Leu Pro Tyr Thr Ile Ile Thr Thr Pro Pro Leu Lys Asp Phe Ser Leu  
               
               
                             3140                3145                3150  
               
               
                   
               
               
                 Trp Glu Lys Thr Gly Leu Lys Glu Phe Leu Lys Thr Thr Lys Gln Ser  
               
               
                         3155                3160                3165  
               
               
                   
               
               
                 Phe Asp Leu Ser Val Lys Ala Gln Tyr Lys Lys Asn Lys His Arg His  
               
               
                     3170                3175                3180  
               
               
                   
               
               
                 Ser Ile Thr Asn Pro Leu Ala Val Leu Cys Glu Phe Ile Ser Gln Ser  
               
               
                 3185                3190                3195                3200  
               
               
                   
               
               
                 Ile Lys Ser Phe Asp Arg His Phe Glu Lys Asn Arg Asn Asn Ala Leu  
               
               
                                 3205                3210                3215  
               
               
                   
               
               
                 Asp Phe Val Thr Lys Ser Tyr Asn Glu Thr Lys Ile Lys Phe Asp Lys  
               
               
                             3220                3225                3230  
               
               
                   
               
               
                 Tyr Lys Ala Glu Lys Ser His Asp Glu Leu Pro Arg Thr Phe Gln Ile  
               
               
                         3235                3240                3245  
               
               
                   
               
               
                 Pro Gly Tyr Thr Val Pro Val Val Asn Val Glu Val Ser Pro Phe Thr  
               
               
                     3250                3255                3260  
               
               
                   
               
               
                 Ile Glu Met Ser Ala Phe Gly Tyr Val Phe Pro Lys Ala Val Ser Met  
               
               
                 3265                3270                3275                3280  
               
               
                   
               
               
                 Pro Ser Phe Ser Ile Leu Gly Ser Asp Val Arg Val Pro Ser Tyr Thr  
               
               
                                 3285                3290                3295  
               
               
                   
               
               
                 Leu Ile Leu Pro Ser Leu Glu Leu Pro Val Leu His Val Pro Arg Asn  
               
               
                             3300                3305                3310  
               
               
                   
               
               
                 Leu Lys Leu Ser Leu Pro His Phe Lys Glu Leu Cys Thr Ile Ser His  
               
               
                         3315                3320                3325  
               
               
                   
               
               
                 Ile Phe Ile Pro Ala Met Gly Asn Ile Thr Tyr Asp Phe Ser Phe Lys  
               
               
                     3330                3335                3340  
               
               
                   
               
               
                 Ser Ser Val Ile Thr Leu Asn Thr Asn Ala Glu Leu Phe Asn Gln Ser  
               
               
                 3345                3350                3355                3360  
               
               
                   
               
               
                 Asp Ile Val Ala His Leu Leu Ser Ser Ser Ser Ser Val Ile Asp Ala  
               
               
                                 3365                3370                3375  
               
               
                   
               
               
                 Leu Gln Tyr Lys Leu Glu Gly Thr Thr Arg Leu Thr Arg Lys Arg Gly  
               
               
                             3380                3385                3390  
               
               
                   
               
               
                 Leu Lys Leu Ala Thr Ala Leu Ser Leu Ser Asn Lys Phe Val Glu Gly  
               
               
                         3395                3400                3405  
               
               
                   
               
               
                 Ser His Asn Ser Thr Val Ser Leu Thr Thr Lys Asn Met Glu Val Ser  
               
               
                     3410                3415                3420  
               
               
                   
               
               
                 Val Ala Lys Thr Thr Lys Ala Glu Ile Pro Ile Leu Arg Met Asn Phe  
               
               
                 3425                3430                3435                3440  
               
               
                   
               
               
                 Lys Gln Glu Leu Asn Gly Asn Thr Lys Ser Lys Pro Thr Val Ser Ser  
               
               
                                 3445                3450                3455  
               
               
                   
               
               
                 Ser Met Glu Phe Lys Tyr Asp Phe Asn Ser Ser Met Leu Tyr Ser Thr  
               
               
                             3460                3465                3470  
               
               
                   
               
               
                 Ala Lys Gly Ala Val Asp His Lys Leu Ser Leu Glu Ser Leu Thr Ser  
               
               
                         3475                3480                3485  
               
               
                   
               
               
                 Tyr Phe Ser Ile Glu Ser Ser Thr Lys Gly Asp Val Lys Gly Ser Val  
               
               
                     3490                3495                3500  
               
               
                   
               
               
                 Leu Ser Arg Glu Tyr Ser Gly Thr Ile Ala Ser Glu Ala Asn Thr Tyr  
               
               
                 3505                3510                3515                3520  
               
               
                   
               
               
                 Leu Asn Ser Lys Ser Thr Arg Ser Ser Val Lys Leu Gln Gly Thr Ser  
               
               
                                 3525                3530                3535  
               
               
                   
               
               
                 Lys Ile Asp Asp Ile Trp Asn Leu Glu Val Lys Glu Asn Phe Ala Gly  
               
               
                             3540                3545                3550  
               
               
                   
               
               
                 Glu Ala Thr Leu Gln Arg Ile Tyr Ser Leu Trp Glu His Ser Thr Lys  
               
               
                         3555                3560                3565  
               
               
                   
               
               
                 Asn His Leu Gln Leu Glu Gly Leu Phe Phe Thr Asn Gly Glu His Thr  
               
               
                     3570                3575                3580  
               
               
                   
               
               
                 Ser Lys Ala Thr Leu Glu Leu Ser Pro Trp Gln Met Ser Ala Leu Val  
               
               
                 3585                3590                3595                3600  
               
               
                   
               
               
                 Gln Val His Ala Ser Gln Pro Ser Ser Phe His Asp Phe Pro Asp Leu  
               
               
                                 3605                3610                3615  
               
               
                   
               
               
                 Gly Gln Glu Val Ala Leu Asn Ala Asn Thr Lys Asn Gln Lys Ile Arg  
               
               
                             3620                3625                3630  
               
               
                   
               
               
                 Trp Lys Asn Glu Val Arg Ile His Ser Gly Ser Phe Gln Ser Gln Val  
               
               
                         3635                3640                3645  
               
               
                   
               
               
                 Glu Leu Ser Asn Asp Gln Glu Lys Ala His Leu Asp Ile Ala Gly Ser  
               
               
                     3650                3655                3660  
               
               
                   
               
               
                 Leu Glu Gly His Leu Arg Phe Leu Lys Asn Ile Ile Leu Pro Val Tyr  
               
               
                 3665                3670                3675                3680  
               
               
                   
               
               
                 Asp Lys Ser Leu Trp Asp Phe Leu Lys Leu Asp Val Thr Thr Ser Ile  
               
               
                                 3685                3690                3695  
               
               
                   
               
               
                 Gly Arg Arg Gln His Leu Arg Val Ser Thr Ala Phe Val Tyr Thr Lys  
               
               
                             3700                3705                3710  
               
               
                   
               
               
                 Asn Pro Asn Gly Tyr Ser Phe Ser Ile Pro Val Lys Val Leu Ala Asp  
               
               
                         3715                3720                3725  
               
               
                   
               
               
                 Lys Phe Ile Thr Pro Gly Leu Lys Leu Asn Asp Leu Asn Ser Val Leu  
               
               
                     3730                3735                3740  
               
               
                   
               
               
                 Val Met Pro Thr Phe His Val Pro Phe Thr Asp Leu Gln Val Pro Ser  
               
               
                 3745                3750                3755                3760  
               
               
                   
               
               
                 Cys Lys Leu Asp Phe Arg Glu Ile Gln Ile Tyr Lys Lys Leu Arg Thr  
               
               
                                 3765                3770                3775  
               
               
                   
               
               
                 Ser Ser Phe Ala Leu Asn Leu Pro Thr Leu Pro Glu Val Lys Phe Pro  
               
               
                             3780                3785                3790  
               
               
                   
               
               
                 Glu Val Asp Val Leu Thr Lys Tyr Ser Gln Pro Glu Asp Ser Leu Ile  
               
               
                         3795                3800                3805  
               
               
                   
               
               
                 Pro Phe Phe Glu Ile Thr Val Pro Glu Ser Gln Leu Thr Val Ser Gln  
               
               
                     3810                3815                3820  
               
               
                   
               
               
                 Phe Thr Leu Pro Lys Ser Val Ser Asp Gly Ile Ala Ala Leu Asp Leu  
               
               
                 3825                3830                3835                3840  
               
               
                   
               
               
                 Asn Ala Val Ala Asn Lys Ile Ala Asp Phe Glu Leu Pro Thr Ile Ile  
               
               
                                 3845                3850                3855  
               
               
                   
               
               
                 Val Pro Glu Gln Thr Ile Glu Ile Pro Ser Ile Lys Phe Ser Val Pro  
               
               
                             3860                3865                3870  
               
               
                   
               
               
                 Ala Gly Ile Val Ile Pro Ser Phe Gln Ala Leu Thr Ala Arg Phe Glu  
               
               
                         3875                3880                3885  
               
               
                   
               
               
                 Val Asp Ser Pro Val Tyr Asn Ala Thr Trp Ser Ala Ser Leu Lys Asn  
               
               
                     3890                3895                3900  
               
               
                   
               
               
                 Lys Ala Asp Tyr Val Glu Thr Val Leu Asp Ser Thr Cys Ser Ser Thr  
               
               
                 3905                3910                3915                3920  
               
               
                   
               
               
                 Val Gln Phe Leu Glu Tyr Glu Leu Asn Val Leu Gly Thr His Lys Ile  
               
               
                                 3925                3930                3935  
               
               
                   
               
               
                 Glu Asp Gly Thr Leu Ala Ser Lys Thr Lys Gly Thr Leu Ala His Arg  
               
               
                             3940                3945                3950  
               
               
                   
               
               
                 Asp Phe Ser Ala Glu Tyr Glu Glu Asp Gly Lys Phe Glu Gly Leu Gln  
               
               
                         3955                3960                3965  
               
               
                   
               
               
                 Glu Trp Glu Gly Lys Ala His Leu Asn Ile Lys Ser Pro Ala Phe Thr  
               
               
                     3970                3975                3980  
               
               
                   
               
               
                 Asp Leu His Leu Arg Tyr Gln Lys Asp Lys Lys Gly Ile Ser Thr Ser  
               
               
                 3985                3990                3995                4000  
               
               
                   
               
               
                 Ala Ala Ser Pro Ala Val Gly Thr Val Gly Met Asp Met Asp Glu Asp  
               
               
                                 4005                4010                4015  
               
               
                   
               
               
                 Asp Asp Phe Ser Lys Trp Asn Phe Tyr Tyr Ser Pro Gln Ser Ser Pro  
               
               
                             4020                4025                4030  
               
               
                   
               
               
                 Asp Lys Lys Leu Thr Ile Phe Lys Thr Glu Leu Arg Val Arg Glu Ser  
               
               
                         4035                4040                4045  
               
               
                   
               
               
                 Asp Glu Glu Thr Gln Ile Lys Val Asn Trp Glu Glu Glu Ala Ala Ser  
               
               
                     4050                4055                4060  
               
               
                   
               
               
                 Gly Leu Leu Thr Ser Leu Lys Asp Asn Val Pro Lys Ala Thr Gly Val  
               
               
                 4065                4070                4075                4080  
               
               
                   
               
               
                 Leu Tyr Asp Tyr Val Asn Lys Tyr His Trp Glu His Thr Gly Leu Thr  
               
               
                                 4085                4090                4095  
               
               
                   
               
               
                 Leu Arg Glu Val Ser Ser Lys Leu Arg Arg Asn Leu Gln Asn Asn Ala  
               
               
                             4100                4105                4110  
               
               
                   
               
               
                 Glu Trp Val Tyr Gln Gly Ala Ile Arg Gln Ile Asp Asp Ile Asp Val  
               
               
                         4115                4120                4125  
               
               
                   
               
               
                 Arg Phe Gln Lys Ala Ala Ser Gly Thr Thr Gly Thr Tyr Gln Glu Trp  
               
               
                     4130                4135                4140  
               
               
                   
               
               
                 Lys Asp Lys Ala Gln Asn Leu Tyr Gln Glu Leu Leu Thr Gln Glu Gly  
               
               
                 4145                4150                4155                4160  
               
               
                   
               
               
                 Gln Ala Ser Phe Gln Gly Leu Lys Asp Asn Val Phe Asp Gly Leu Val  
               
               
                                 4165                4170                4175  
               
               
                   
               
               
                 Arg Val Thr Gln Lys Phe His Met Lys Val Lys His Leu Ile Asp Ser  
               
               
                             4180                4185                4190  
               
               
                   
               
               
                 Leu Ile Asp Phe Leu Asn Phe Pro Arg Phe Gln Phe Pro Gly Lys Pro  
               
               
                         4195                4200                4205  
               
               
                   
               
               
                 Gly Ile Tyr Thr Arg Glu Glu Leu Cys Thr Met Phe Ile Arg Glu Val  
               
               
                     4210                4215                4220  
               
               
                   
               
               
                 Gly Thr Val Leu Ser Gln Val Tyr Ser Lys Val His Asn Gly Ser Glu  
               
               
                 4225                4230                4235                4240  
               
               
                   
               
               
                 Ile Leu Phe Ser Tyr Phe Gln Asp Leu Val Ile Thr Leu Pro Phe Glu  
               
               
                                 4245                4250                4255  
               
               
                   
               
               
                 Leu Arg Lys His Lys Leu Ile Asp Val Ile Ser Met Tyr Arg Glu Leu  
               
               
                             4260                4265                4270  
               
               
                   
               
               
                 Leu Lys Asp Leu Ser Lys Glu Ala Gln Glu Val Phe Lys Ala Ile Gln  
               
               
                         4275                4280                4285  
               
               
                   
               
               
                 Ser Leu Lys Thr Thr Glu Val Leu Arg Asn Leu Gln Asp Leu Leu Gln  
               
               
                     4290                4295                4300  
               
               
                   
               
               
                 Phe Ile Phe Gln Leu Ile Glu Asp Asn Ile Lys Gln Leu Lys Glu Met  
               
               
                 4305                4310                4315                4320  
               
               
                   
               
               
                 Lys Phe Thr Tyr Leu Ile Asn Tyr Ile Gln Asp Glu Ile Asn Thr Ile  
               
               
                                 4325                4330                4335  
               
               
                   
               
               
                 Phe Asn Asp Tyr Ile Pro Tyr Val Phe Lys Leu Leu Lys Glu Asn Leu  
               
               
                             4340                4345                4350  
               
               
                   
               
               
                 Cys Leu Asn Leu His Lys Phe Asn Glu Phe Ile Gln Asn Glu Leu Gln  
               
               
                         4355                4360                4365  
               
               
                   
               
               
                 Glu Ala Ser Gln Glu Leu Gln Gln Ile His Gln Tyr Ile Met Ala Leu  
               
               
                     4370                4375                4380  
               
               
                   
               
               
                 Arg Glu Glu Tyr Phe Asp Pro Ser Ile Val Gly Trp Thr Val Lys Tyr  
               
               
                 4385                4390                4395                4400  
               
               
                   
               
               
                 Tyr Glu Leu Glu Glu Lys Ile Val Ser Leu Ile Lys Asn Leu Leu Val  
               
               
                                 4405                4410                4415  
               
               
                   
               
               
                 Ala Leu Lys Asp Phe His Ser Glu Tyr Ile Val Ser Ala Ser Asn Phe  
               
               
                             4420                4425                4430  
               
               
                   
               
               
                 Thr Ser Gln Leu Ser Ser Gln Val Glu Gln Phe Leu His Arg Asn Ile  
               
               
                         4435                4440                4445  
               
               
                   
               
               
                 Gln Glu Tyr Leu Ser Ile Leu Thr Asp Pro Asp Gly Lys Gly Lys Glu  
               
               
                     4450                4455                4460  
               
               
                   
               
               
                 Lys Ile Ala Glu Leu Ser Ala Thr Ala Gln Glu Ile Ile Lys Ser Gln  
               
               
                 4465                4470                4475                4480  
               
               
                   
               
               
                 Ala Ile Ala Thr Lys Lys Ile Ile Ser Asp Tyr His Gln Gln Phe Arg  
               
               
                                 4485                4490                4495  
               
               
                   
               
               
                 Tyr Lys Leu Gln Asp Phe Ser Asp Gln Leu Ser Asp Tyr Tyr Glu Lys  
               
               
                             4500                4505                4510  
               
               
                   
               
               
                 Phe Ile Ala Glu Ser Lys Arg Leu Ile Asp Leu Ser Ile Gln Asn Tyr  
               
               
                         4515                4520                4525  
               
               
                   
               
               
                 His Thr Phe Leu Ile Tyr Ile Thr Glu Leu Leu Lys Lys Leu Gln Ser  
               
               
                     4530                4535                4540  
               
               
                   
               
               
                 Thr Thr Val Met Asn Pro Tyr Met Lys Leu Ala Pro Gly Glu Leu Thr  
               
               
                 4545                4550                4555                4560  
               
               
                   
               
               
                 Ile Ile Leu  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 33  
               
               
                 &lt;211&gt; LENGTH: 2196  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (13)...(1983)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding  
               
               
                       5,10-methylenetetrahydofolate reductase (MTHFR)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 33  
               
               
                   
               
               
                 aattccggag cc atg gtg aac gaa gcc aga gga aac agc agc ctc aac ccc     51  
               
               
                               Met Val Asn Glu Ala Arg Gly Asn Ser Ser Leu Asn Pro  
               
               
                                1               5                   10  
               
               
                   
               
               
                 tgc ttg gag ggc agt gcc agc agt ggc agt gag agc tcc aaa gat agt       99  
               
               
                 Cys Leu Glu Gly Ser Ala Ser Ser Gly Ser Glu Ser Ser Lys Asp Ser  
               
               
                      15                  20                  25  
               
               
                   
               
               
                 tcg aga tgt tcc acc ccg ggc ctg gac cct gag cgg cat gag aga ctc      147  
               
               
                 Ser Arg Cys Ser Thr Pro Gly Leu Asp Pro Glu Arg His Glu Arg Leu  
               
               
                  30                  35                  40                  45  
               
               
                   
               
               
                 cgg gag aag atg agg cgg cga ttg gaa tct ggt gac aag tgg ttc tcc      195  
               
               
                 Arg Glu Lys Met Arg Arg Arg Leu Glu Ser Gly Asp Lys Trp Phe Ser  
               
               
                                  50                  55                  60  
               
               
                   
               
               
                 ctg gaa ttc ttc cct cct cga act gct gag gga gct gtc aat ctc atc      243  
               
               
                 Leu Glu Phe Phe Pro Pro Arg Thr Ala Glu Gly Ala Val Asn Leu Ile  
               
               
                              65                  70                  75  
               
               
                   
               
               
                 tca agg ttt gac cgg atg gca gca ggt ggc ccc ctc tac ata gac gtg      291  
               
               
                 Ser Arg Phe Asp Arg Met Ala Ala Gly Gly Pro Leu Tyr Ile Asp Val  
               
               
                          80                  85                  90  
               
               
                   
               
               
                 acc tgg cac cca gca ggt gac cct ggc tca gac aag gag acc tcc tcc      339  
               
               
                 Thr Trp His Pro Ala Gly Asp Pro Gly Ser Asp Lys Glu Thr Ser Ser  
               
               
                      95                 100                 105  
               
               
                   
               
               
                 atg atg atc gcc agc acc gcc gtg aac tac tgt ggc ctg gag acc atc      387  
               
               
                 Met Met Ile Ala Ser Thr Ala Val Asn Tyr Cys Gly Leu Glu Thr Ile  
               
               
                 110                 115                 120                 125  
               
               
                   
               
               
                 ctg cac atg acc tgc tgc cgt cag cgc ctg gag gag atc acg ggc cat      435  
               
               
                 Leu His Met Thr Cys Cys Arg Gln Arg Leu Glu Glu Ile Thr Gly His  
               
               
                                 130                 135                 140  
               
               
                   
               
               
                 ctg cac aaa gct aag cag ctg ggc ctg aag aac atc atg gcg ctg cgg      483  
               
               
                 Leu His Lys Ala Lys Gln Leu Gly Leu Lys Asn Ile Met Ala Leu Arg  
               
               
                             145                 150                 155  
               
               
                   
               
               
                 gga gac cca ata ggt gac cag tgg gaa gag gag gag gga ggc ttc aac      531  
               
               
                 Gly Asp Pro Ile Gly Asp Gln Trp Glu Glu Glu Glu Gly Gly Phe Asn  
               
               
                         160                 165                 170  
               
               
                   
               
               
                 tac gca gtg gac ctg gtg aag cac atc cga agt gag ttt ggt gac tac      579  
               
               
                 Tyr Ala Val Asp Leu Val Lys His Ile Arg Ser Glu Phe Gly Asp Tyr  
               
               
                     175                 180                 185  
               
               
                   
               
               
                 ttt gac atc tgt gtg gca ggt tac ccc aaa ggc cac ccc gaa gca ggg      627  
               
               
                 Phe Asp Ile Cys Val Ala Gly Tyr Pro Lys Gly His Pro Glu Ala Gly  
               
               
                 190                 195                 200                 205  
               
               
                   
               
               
                 agc ttt gag gct gac ctg aag cac ttg aag gag aag gtg tct gcg gga      675  
               
               
                 Ser Phe Glu Ala Asp Leu Lys His Leu Lys Glu Lys Val Ser Ala Gly  
               
               
                                 210                 215                 220  
               
               
                   
               
               
                 gcc gat ttc atc atc acg cag ctt ttc ttt gag gct gac aca ttc ttc      723  
               
               
                 Ala Asp Phe Ile Ile Thr Gln Leu Phe Phe Glu Ala Asp Thr Phe Phe  
               
               
                             225                 230                 235  
               
               
                   
               
               
                 cgc ttt gtg aag gca tgc acc gac atg ggc atc act tgc ccc atc gtc      771  
               
               
                 Arg Phe Val Lys Ala Cys Thr Asp Met Gly Ile Thr Cys Pro Ile Val  
               
               
                         240                 245                 250  
               
               
                   
               
               
                 ccc ggg atc ttt ccc atc cag ggc tac cac tcc ctt cgg cag ctt gtg      819  
               
               
                 Pro Gly Ile Phe Pro Ile Gln Gly Tyr His Ser Leu Arg Gln Leu Val  
               
               
                     255                 260                 265  
               
               
                   
               
               
                 aag ctg tcc aag ctg gag gtg cca cag gag atc aag gac gtg att gag      867  
               
               
                 Lys Leu Ser Lys Leu Glu Val Pro Gln Glu Ile Lys Asp Val Ile Glu  
               
               
                 270                 275                 280                 285  
               
               
                   
               
               
                 cca atc aaa gac aac gat gct gcc atc cgc aac tat ggc atc gag ctg      915  
               
               
                 Pro Ile Lys Asp Asn Asp Ala Ala Ile Arg Asn Tyr Gly Ile Glu Leu  
               
               
                                 290                 295                 300  
               
               
                   
               
               
                 gcc gtg agc ctg tgc cag gag ctt ctg gcc agt ggc ttg gtg cca ggc      963  
               
               
                 Ala Val Ser Leu Cys Gln Glu Leu Leu Ala Ser Gly Leu Val Pro Gly  
               
               
                             305                 310                 315  
               
               
                   
               
               
                 ctc cac ttc tac acc ctc aac cgc gag atg gct acc aca gag gtg ctg     1011  
               
               
                 Leu His Phe Tyr Thr Leu Asn Arg Glu Met Ala Thr Thr Glu Val Leu  
               
               
                         320                 325                 330  
               
               
                   
               
               
                 aag cgc ctg ggg atg tgg act gag gac ccc agg cgt ccc cta ccc tgg     1059  
               
               
                 Lys Arg Leu Gly Met Trp Thr Glu Asp Pro Arg Arg Pro Leu Pro Trp  
               
               
                     335                 340                 345  
               
               
                   
               
               
                 gct ctc agt gcc cac ccc aag cgc cga gag gaa gat gta cgt ccc atc     1107  
               
               
                 Ala Leu Ser Ala His Pro Lys Arg Arg Glu Glu Asp Val Arg Pro Ile  
               
               
                 350                 355                 360                 365  
               
               
                   
               
               
                 ttc tgg gcc tcc aga cca aag agt tac atc tac cgt acc cag gag tgg     1155  
               
               
                 Phe Trp Ala Ser Arg Pro Lys Ser Tyr Ile Tyr Arg Thr Gln Glu Trp  
               
               
                                 370                 375                 380  
               
               
                   
               
               
                 gac gag ttc cct aac ggc cgc tgg ggc aat tcc tct tcc cct gcc ttt     1203  
               
               
                 Asp Glu Phe Pro Asn Gly Arg Trp Gly Asn Ser Ser Ser Pro Ala Phe  
               
               
                             385                 390                 395  
               
               
                   
               
               
                 ggg gag ctg aag gac tac tac ctc ttc tac ctg aag agc aag tcc ccc     1251  
               
               
                 Gly Glu Leu Lys Asp Tyr Tyr Leu Phe Tyr Leu Lys Ser Lys Ser Pro  
               
               
                         400                 405                 410  
               
               
                   
               
               
                 aag gag gag ctg ctg aag atg tgg ggg gag gag ctg acc agt gaa gca     1299  
               
               
                 Lys Glu Glu Leu Leu Lys Met Trp Gly Glu Glu Leu Thr Ser Glu Ala  
               
               
                     415                 420                 425  
               
               
                   
               
               
                 agt gtc ttt gaa gtc ttt gtt ctt tac ctc tcg gga gaa cca aac cgg     1347  
               
               
                 Ser Val Phe Glu Val Phe Val Leu Tyr Leu Ser Gly Glu Pro Asn Arg  
               
               
                 430                 435                 440                 445  
               
               
                   
               
               
                 aat ggt cac aaa gtg act tgc ctg ccc tgg aac gat gag ccc ctg gcg     1395  
               
               
                 Asn Gly His Lys Val Thr Cys Leu Pro Trp Asn Asp Glu Pro Leu Ala  
               
               
                                 450                 455                 460  
               
               
                   
               
               
                 gct gag acc agc ctg ctg aag gag gag ctg ctg cgg gtg aac cgc cag     1443  
               
               
                 Ala Glu Thr Ser Leu Leu Lys Glu Glu Leu Leu Arg Val Asn Arg Gln  
               
               
                             465                 470                 475  
               
               
                   
               
               
                 ggc atc ctc acc atc aac tca cag ccc aac atc aac ggg aag ccg tcc     1491  
               
               
                 Gly Ile Leu Thr Ile Asn Ser Gln Pro Asn Ile Asn Gly Lys Pro Ser  
               
               
                         480                 485                 490  
               
               
                   
               
               
                 tcc gac ccc atc gtg ggc tgg ggc ccc agc ggg ggc tat gtc ttc cag     1539  
               
               
                 Ser Asp Pro Ile Val Gly Trp Gly Pro Ser Gly Gly Tyr Val Phe Gln  
               
               
                     495                 500                 505  
               
               
                   
               
               
                 aag gcc tac tta gag ttt ttc act tcc cgc gag aca gcg gaa gca ctt     1587  
               
               
                 Lys Ala Tyr Leu Glu Phe Phe Thr Ser Arg Glu Thr Ala Glu Ala Leu  
               
               
                 510                 515                 520                 525  
               
               
                   
               
               
                 ctg caa gtg ctg aag aag tac gag ctc cgg gtt aat tac cac ctt gtc     1635  
               
               
                 Leu Gln Val Leu Lys Lys Tyr Glu Leu Arg Val Asn Tyr His Leu Val  
               
               
                                 530                 535                 540  
               
               
                   
               
               
                 aat gtg aag ggt gaa aac atc acc aat gcc cct gaa ctg cag ccg aat     1683  
               
               
                 Asn Val Lys Gly Glu Asn Ile Thr Asn Ala Pro Glu Leu Gln Pro Asn  
               
               
                             545                 550                 555  
               
               
                   
               
               
                 gct gtc act tgg ggc atc ttc cct ggg cga gag atc atc cag ccc acc     1731  
               
               
                 Ala Val Thr Trp Gly Ile Phe Pro Gly Arg Glu Ile Ile Gln Pro Thr  
               
               
                         560                 565                 570  
               
               
                   
               
               
                 gta gtg gat ccc gtc agc ttc atg ttc tgg aag gac gag gcc ttt gcc     1779  
               
               
                 Val Val Asp Pro Val Ser Phe Met Phe Trp Lys Asp Glu Ala Phe Ala  
               
               
                     575                 580                 585  
               
               
                   
               
               
                 ctg tgg att gag cgg tgg gga aag ctg tat gag gag gag tcc ccg tcc     1827  
               
               
                 Leu Trp Ile Glu Arg Trp Gly Lys Leu Tyr Glu Glu Glu Ser Pro Ser  
               
               
                 590                 595                 600                 605  
               
               
                   
               
               
                 cgc acc atc atc cag tac atc cac gac aac tac ttc ctg gtc aac ctg     1875  
               
               
                 Arg Thr Ile Ile Gln Tyr Ile His Asp Asn Tyr Phe Leu Val Asn Leu  
               
               
                                 610                 615                 620  
               
               
                   
               
               
                 gtg gac aat gac ttc cca ctg gac aac tgc ctc tgg cag gtg gtg gaa     1923  
               
               
                 Val Asp Asn Asp Phe Pro Leu Asp Asn Cys Leu Trp Gln Val Val Glu  
               
               
                             625                 630                 635  
               
               
                   
               
               
                 gac aca ttg gag ctt ctc aac agg ccc acc cag aat gcg aga gaa acg     1971  
               
               
                 Asp Thr Leu Glu Leu Leu Asn Arg Pro Thr Gln Asn Ala Arg Glu Thr  
               
               
                         640                 645                 650  
               
               
                   
               
               
                 gag gct cca tga ccctgcgtcc tgacgccctg cgttggagcc actcctgtcc         2023  
               
               
                 Glu Ala Pro  *  
               
               
                     655  
               
               
                   
               
               
                 cgccttcctc ctccacagtg ctgcttctct tgggaactcc actctccttc gtgtctctcc   2083  
               
               
                   
               
               
                 caccccggcc tccactcccc cacctgacaa tggcagctag actggagtga ggcttccagg   2143  
               
               
                   
               
               
                 ctcttcctgg acctgagtcg gccccacatg ggaacctagt actctctgct cta          2196  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 34  
               
               
                 &lt;211&gt; LENGTH: 656  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 34  
               
               
                   
               
               
                 Met Val Asn Glu Ala Arg Gly Asn Ser Ser Leu Asn Pro Cys Leu Glu  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gly Ser Ala Ser Ser Gly Ser Glu Ser Ser Lys Asp Ser Ser Arg Cys  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Ser Thr Pro Gly Leu Asp Pro Glu Arg His Glu Arg Leu Arg Glu Lys  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Met Arg Arg Arg Leu Glu Ser Gly Asp Lys Trp Phe Ser Leu Glu Phe  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Phe Pro Pro Arg Thr Ala Glu Gly Ala Val Asn Leu Ile Ser Arg Phe  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Asp Arg Met Ala Ala Gly Gly Pro Leu Tyr Ile Asp Val Thr Trp His  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Pro Ala Gly Asp Pro Gly Ser Asp Lys Glu Thr Ser Ser Met Met Ile  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ala Ser Thr Ala Val Asn Tyr Cys Gly Leu Glu Thr Ile Leu His Met  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Thr Cys Cys Arg Gln Arg Leu Glu Glu Ile Thr Gly His Leu His Lys  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ala Lys Gln Leu Gly Leu Lys Asn Ile Met Ala Leu Arg Gly Asp Pro  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ile Gly Asp Gln Trp Glu Glu Glu Glu Gly Gly Phe Asn Tyr Ala Val  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Asp Leu Val Lys His Ile Arg Ser Glu Phe Gly Asp Tyr Phe Asp Ile  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Cys Val Ala Gly Tyr Pro Lys Gly His Pro Glu Ala Gly Ser Phe Glu  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Asp Leu Lys His Leu Lys Glu Lys Val Ser Ala Gly Ala Asp Phe  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ile Ile Thr Gln Leu Phe Phe Glu Ala Asp Thr Phe Phe Arg Phe Val  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Lys Ala Cys Thr Asp Met Gly Ile Thr Cys Pro Ile Val Pro Gly Ile  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Phe Pro Ile Gln Gly Tyr His Ser Leu Arg Gln Leu Val Lys Leu Ser  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Lys Leu Glu Val Pro Gln Glu Ile Lys Asp Val Ile Glu Pro Ile Lys  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Asp Asn Asp Ala Ala Ile Arg Asn Tyr Gly Ile Glu Leu Ala Val Ser  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Leu Cys Gln Glu Leu Leu Ala Ser Gly Leu Val Pro Gly Leu His Phe  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Tyr Thr Leu Asn Arg Glu Met Ala Thr Thr Glu Val Leu Lys Arg Leu  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Gly Met Trp Thr Glu Asp Pro Arg Arg Pro Leu Pro Trp Ala Leu Ser  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ala His Pro Lys Arg Arg Glu Glu Asp Val Arg Pro Ile Phe Trp Ala  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Ser Arg Pro Lys Ser Tyr Ile Tyr Arg Thr Gln Glu Trp Asp Glu Phe  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Pro Asn Gly Arg Trp Gly Asn Ser Ser Ser Pro Ala Phe Gly Glu Leu  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Lys Asp Tyr Tyr Leu Phe Tyr Leu Lys Ser Lys Ser Pro Lys Glu Glu  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Leu Leu Lys Met Trp Gly Glu Glu Leu Thr Ser Glu Ala Ser Val Phe  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Glu Val Phe Val Leu Tyr Leu Ser Gly Glu Pro Asn Arg Asn Gly His  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Lys Val Thr Cys Leu Pro Trp Asn Asp Glu Pro Leu Ala Ala Glu Thr  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Ser Leu Leu Lys Glu Glu Leu Leu Arg Val Asn Arg Gln Gly Ile Leu  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Thr Ile Asn Ser Gln Pro Asn Ile Asn Gly Lys Pro Ser Ser Asp Pro  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Ile Val Gly Trp Gly Pro Ser Gly Gly Tyr Val Phe Gln Lys Ala Tyr  
               
               
                             500                 505                 510  
               
               
                   
               
               
                 Leu Glu Phe Phe Thr Ser Arg Glu Thr Ala Glu Ala Leu Leu Gln Val  
               
               
                         515                 520                 525  
               
               
                   
               
               
                 Leu Lys Lys Tyr Glu Leu Arg Val Asn Tyr His Leu Val Asn Val Lys  
               
               
                     530                 535                 540  
               
               
                   
               
               
                 Gly Glu Asn Ile Thr Asn Ala Pro Glu Leu Gln Pro Asn Ala Val Thr  
               
               
                 545                 550                 555                 560  
               
               
                   
               
               
                 Trp Gly Ile Phe Pro Gly Arg Glu Ile Ile Gln Pro Thr Val Val Asp  
               
               
                                 565                 570                 575  
               
               
                   
               
               
                 Pro Val Ser Phe Met Phe Trp Lys Asp Glu Ala Phe Ala Leu Trp Ile  
               
               
                             580                 585                 590  
               
               
                   
               
               
                 Glu Arg Trp Gly Lys Leu Tyr Glu Glu Glu Ser Pro Ser Arg Thr Ile  
               
               
                         595                 600                 605  
               
               
                   
               
               
                 Ile Gln Tyr Ile His Asp Asn Tyr Phe Leu Val Asn Leu Val Asp Asn  
               
               
                     610                 615                 620  
               
               
                   
               
               
                 Asp Phe Pro Leu Asp Asn Cys Leu Trp Gln Val Val Glu Asp Thr Leu  
               
               
                 625                 630                 635                 640  
               
               
                   
               
               
                 Glu Leu Leu Asn Arg Pro Thr Gln Asn Ala Arg Glu Thr Glu Ala Pro  
               
               
                                 645                 650                 655  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 35  
               
               
                 &lt;211&gt; LENGTH: 3834  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (117)...(1949)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding selectin E (SELE)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 35  
               
               
                   
               
               
                 cctgagacag aggcagcagt gatacccacc tgagagatcc tgtgtttgaa caactgcttc     60  
               
               
                   
               
               
                 ccaaaacgga aagtatttca agcctaaacc tttgggtgaa aagaactctt gaagtc atg    119  
               
               
                                                                               Met  
               
               
                                                                                1  
               
               
                   
               
               
                 att gct tca cag ttt ctc tca gct ctc act ttg gtg ctt ctc att aaa      167  
               
               
                 Ile Ala Ser Gln Phe Leu Ser Ala Leu Thr Leu Val Leu Leu Ile Lys  
               
               
                              5                   10                  15  
               
               
                   
               
               
                 gag agt gga gcc tgg tct tac aac acc tcc acg gaa gct atg act tat      215  
               
               
                 Glu Ser Gly Ala Trp Ser Tyr Asn Thr Ser Thr Glu Ala Met Thr Tyr  
               
               
                          20                  25                  30  
               
               
                   
               
               
                 gat gag gcc agt gct tat tgt cag caa agg tac aca cac ctg gtt gca      263  
               
               
                 Asp Glu Ala Ser Ala Tyr Cys Gln Gln Arg Tyr Thr His Leu Val Ala  
               
               
                      35                  40                  45  
               
               
                   
               
               
                 att caa aac aaa gaa gag att gag tac cta aac tcc ata ttg agc tat      311  
               
               
                 Ile Gln Asn Lys Glu Glu Ile Glu Tyr Leu Asn Ser Ile Leu Ser Tyr  
               
               
                  50                  55                  60                  65  
               
               
                   
               
               
                 tca cca agt tat tac tgg att gga atc aga aaa gtc aac aat gtg tgg      359  
               
               
                 Ser Pro Ser Tyr Tyr Trp Ile Gly Ile Arg Lys Val Asn Asn Val Trp  
               
               
                                  70                  75                  80  
               
               
                   
               
               
                 gtc tgg gta gga acc cag aaa cct ctg aca gaa gaa gcc aag aac tgg      407  
               
               
                 Val Trp Val Gly Thr Gln Lys Pro Leu Thr Glu Glu Ala Lys Asn Trp  
               
               
                              85                  90                  95  
               
               
                   
               
               
                 gct cca ggt gaa ccc aac aat agg caa aaa gat gag gac tgc gtg gag      455  
               
               
                 Ala Pro Gly Glu Pro Asn Asn Arg Gln Lys Asp Glu Asp Cys Val Glu  
               
               
                         100                 105                 110  
               
               
                   
               
               
                 atc tac atc aag aga gaa aaa gat gtg ggc atg tgg aat gat gag agg      503  
               
               
                 Ile Tyr Ile Lys Arg Glu Lys Asp Val Gly Met Trp Asn Asp Glu Arg  
               
               
                     115                 120                 125  
               
               
                   
               
               
                 tgc agc aag aag aag ctt gcc cta tgc tac aca gct gcc tgt acc aat      551  
               
               
                 Cys Ser Lys Lys Lys Leu Ala Leu Cys Tyr Thr Ala Ala Cys Thr Asn  
               
               
                 130                 135                 140                 145  
               
               
                   
               
               
                 aca tcc tgc agt ggc cac ggt gaa tgt gta gag acc atc aat aat tac      599  
               
               
                 Thr Ser Cys Ser Gly His Gly Glu Cys Val Glu Thr Ile Asn Asn Tyr  
               
               
                                 150                 155                 160  
               
               
                   
               
               
                 act tgc aag tgt gac cct ggc ttc agt gga ctc aag tgt gag caa att      647  
               
               
                 Thr Cys Lys Cys Asp Pro Gly Phe Ser Gly Leu Lys Cys Glu Gln Ile  
               
               
                             165                 170                 175  
               
               
                   
               
               
                 gtg aac tgt aca gcc ctg gaa tcc cct gag cat gga agc ctg gtt tgc      695  
               
               
                 Val Asn Cys Thr Ala Leu Glu Ser Pro Glu His Gly Ser Leu Val Cys  
               
               
                         180                 185                 190  
               
               
                   
               
               
                 agt cac cca ctg gga aac ttc agc tac aat tct tcc tgc tct atc agc      743  
               
               
                 Ser His Pro Leu Gly Asn Phe Ser Tyr Asn Ser Ser Cys Ser Ile Ser  
               
               
                     195                 200                 205  
               
               
                   
               
               
                 tgt gat agg ggt tac ctg cca agc agc atg gag acc atg cag tgt atg      791  
               
               
                 Cys Asp Arg Gly Tyr Leu Pro Ser Ser Met Glu Thr Met Gln Cys Met  
               
               
                 210                 215                 220                 225  
               
               
                   
               
               
                 tcc tct gga gaa tgg agt gct cct att cca gcc tgc aat gtg gtt gag      839  
               
               
                 Ser Ser Gly Glu Trp Ser Ala Pro Ile Pro Ala Cys Asn Val Val Glu  
               
               
                                 230                 235                 240  
               
               
                   
               
               
                 tgt gat gct gtg aca aat cca gcc aat ggg ttc gtg gaa tgt ttc caa      887  
               
               
                 Cys Asp Ala Val Thr Asn Pro Ala Asn Gly Phe Val Glu Cys Phe Gln  
               
               
                             245                 250                 255  
               
               
                   
               
               
                 aac cct gga agc ttc cca tgg aac aca acc tgt aca ttt gac tgt gaa      935  
               
               
                 Asn Pro Gly Ser Phe Pro Trp Asn Thr Thr Cys Thr Phe Asp Cys Glu  
               
               
                         260                 265                 270  
               
               
                   
               
               
                 gaa gga ttt gaa cta atg gga gcc cag agc ctt cag tgt acc tca tct      983  
               
               
                 Glu Gly Phe Glu Leu Met Gly Ala Gln Ser Leu Gln Cys Thr Ser Ser  
               
               
                     275                 280                 285  
               
               
                   
               
               
                 ggg aat tgg gac aac gag aag cca acg tgt aaa gct gtg aca tgc agg     1031  
               
               
                 Gly Asn Trp Asp Asn Glu Lys Pro Thr Cys Lys Ala Val Thr Cys Arg  
               
               
                 290                 295                 300                 305  
               
               
                   
               
               
                 gcc gtc cgc cag cct cag aat ggc tct gtg agg tgc agc cat tcc cct     1079  
               
               
                 Ala Val Arg Gln Pro Gln Asn Gly Ser Val Arg Cys Ser His Ser Pro  
               
               
                                 310                 315                 320  
               
               
                   
               
               
                 gct gga gag ttc acc ttc aaa tca tcc tgc aac ttc acc tgt gag gaa     1127  
               
               
                 Ala Gly Glu Phe Thr Phe Lys Ser Ser Cys Asn Phe Thr Cys Glu Glu  
               
               
                             325                 330                 335  
               
               
                   
               
               
                 ggc ttc atg ttg cag gga cca gcc cag gtt gaa tgc acc act caa ggg     1175  
               
               
                 Gly Phe Met Leu Gln Gly Pro Ala Gln Val Glu Cys Thr Thr Gln Gly  
               
               
                         340                 345                 350  
               
               
                   
               
               
                 cag tgg aca cag caa atc cca gtt tgt gaa gct ttc cag tgc aca gcc     1223  
               
               
                 Gln Trp Thr Gln Gln Ile Pro Val Cys Glu Ala Phe Gln Cys Thr Ala  
               
               
                     355                 360                 365  
               
               
                   
               
               
                 ttg tcc aac ccc gag cga ggc tac atg aat tgt ctt cct agt gct tct     1271  
               
               
                 Leu Ser Asn Pro Glu Arg Gly Tyr Met Asn Cys Leu Pro Ser Ala Ser  
               
               
                 370                 375                 380                 385  
               
               
                   
               
               
                 ggc agt ttc cgt tat ggg tcc agc tgt gag ttc tcc tgt gag cag ggt     1319  
               
               
                 Gly Ser Phe Arg Tyr Gly Ser Ser Cys Glu Phe Ser Cys Glu Gln Gly  
               
               
                                 390                 395                 400  
               
               
                   
               
               
                 ttt gtg ttg aag gga tcc aaa agg ctc caa tgt ggc ccc aca ggg gag     1367  
               
               
                 Phe Val Leu Lys Gly Ser Lys Arg Leu Gln Cys Gly Pro Thr Gly Glu  
               
               
                             405                 410                 415  
               
               
                   
               
               
                 tgg gac aac gag aag ccc aca tgt gaa gct gtg aga tgc gat gct gtc     1415  
               
               
                 Trp Asp Asn Glu Lys Pro Thr Cys Glu Ala Val Arg Cys Asp Ala Val  
               
               
                         420                 425                 430  
               
               
                   
               
               
                 cac cag ccc ccg aag ggt ttg gtg agg tgt gct cat tcc cct att gga     1463  
               
               
                 His Gln Pro Pro Lys Gly Leu Val Arg Cys Ala His Ser Pro Ile Gly  
               
               
                     435                 440                 445  
               
               
                   
               
               
                 gaa ttc acc tac aag tcc tct tgt gcc ttc agc tgt gag gag gga ttt     1511  
               
               
                 Glu Phe Thr Tyr Lys Ser Ser Cys Ala Phe Ser Cys Glu Glu Gly Phe  
               
               
                 450                 455                 460                 465  
               
               
                   
               
               
                 gaa tta tat gga tca act caa ctt gag tgc aca tct cag gga caa tgg     1559  
               
               
                 Glu Leu Tyr Gly Ser Thr Gln Leu Glu Cys Thr Ser Gln Gly Gln Trp  
               
               
                                 470                 475                 480  
               
               
                   
               
               
                 aca gaa gag gtt cct tcc tgc caa gtg gta aaa tgt tca agc ctg gca     1607  
               
               
                 Thr Glu Glu Val Pro Ser Cys Gln Val Val Lys Cys Ser Ser Leu Ala  
               
               
                             485                 490                 495  
               
               
                   
               
               
                 gtt ccg gga aag atc aac atg agc tgc agt ggg gag ccc gtg ttt ggc     1655  
               
               
                 Val Pro Gly Lys Ile Asn Met Ser Cys Ser Gly Glu Pro Val Phe Gly  
               
               
                         500                 505                 510  
               
               
                   
               
               
                 act gtg tgc aag ttc gcc tgt cct gaa gga tgg acg ctc aat ggc tct     1703  
               
               
                 Thr Val Cys Lys Phe Ala Cys Pro Glu Gly Trp Thr Leu Asn Gly Ser  
               
               
                     515                 520                 525  
               
               
                   
               
               
                 gca gct cgg aca tgt gga gcc aca gga cac tgg tct ggc ctg cta cct     1751  
               
               
                 Ala Ala Arg Thr Cys Gly Ala Thr Gly His Trp Ser Gly Leu Leu Pro  
               
               
                 530                 535                 540                 545  
               
               
                   
               
               
                 acc tgt gaa gct ccc act gag tcc aac att ccc ttg gta gct gga ctt     1799  
               
               
                 Thr Cys Glu Ala Pro Thr Glu Ser Asn Ile Pro Leu Val Ala Gly Leu  
               
               
                                 550                 555                 560  
               
               
                   
               
               
                 tct gct gct gga ctc tcc ctc ctg aca tta gca cca ttt ctc ctc tgg     1847  
               
               
                 Ser Ala Ala Gly Leu Ser Leu Leu Thr Leu Ala Pro Phe Leu Leu Trp  
               
               
                             565                 570                 575  
               
               
                   
               
               
                 ctt cgg aaa tgc tta cgg aaa gca aag aaa ttt gtt cct gcc agc agc     1895  
               
               
                 Leu Arg Lys Cys Leu Arg Lys Ala Lys Lys Phe Val Pro Ala Ser Ser  
               
               
                         580                 585                 590  
               
               
                   
               
               
                 tgc caa agc ctt gaa tca gac gga agc tac caa aag cct tct tac atc     1943  
               
               
                 Cys Gln Ser Leu Glu Ser Asp Gly Ser Tyr Gln Lys Pro Ser Tyr Ile  
               
               
                     595                 600                 605  
               
               
                   
               
               
                 ctt taa gttcaaaaga atcagaaaca ggtgcatctg gggaactaga gggatacact      1999  
               
               
                 Leu  *  
               
               
                 610  
               
               
                   
               
               
                 gaagttaaca gagacagata actctcctcg ggtctctggc ccttcttgcc tactatgcca   2059  
               
               
                   
               
               
                 gatgccttta tggctgaaac cgcaacaccc atcaccactt caatagatca aagtccagca   2119  
               
               
                   
               
               
                 ggcaaggacg gccttcaact gaaaagactc agtgttccct ttcctactct caggatcaag   2179  
               
               
                   
               
               
                 aaagtgttgg ctaatgaagg gaaaggatat tttcttccaa gcaaaggtga agagaccaag   2239  
               
               
                   
               
               
                 actctgaaat ctcagaattc cttttctaac tctcccttgc tcgctgtaaa atcttggcac   2299  
               
               
                   
               
               
                 agaaacacaa tattttgtgg ctttctttct tttgcccttc acagtgtttc gacagctgat   2359  
               
               
                   
               
               
                 tacacagttg ctgtcataag aatgaataat aattatccag agtttagagg aaaaaaatga   2419  
               
               
                   
               
               
                 ctaaaaatat tataacttaa aaaaatgaca gatgttgaat gcccacaggc aaatgcatgg   2479  
               
               
                   
               
               
                 agggttgtta atggtgcaaa tcctactgaa tgctctgtgc gagggttact atgcacaatt   2539  
               
               
                   
               
               
                 taatcacttt catccctatg ggattcagtg cttcttaaag agttcttaag gattgtgata   2599  
               
               
                   
               
               
                 tttttacttg cattgaatat attataatct tccatacttc ttcattcaat acaagtgtgg   2659  
               
               
                   
               
               
                 tagggactta aaaaacttgt aaatgctgtc aactatgata tggtaaaagt tacttattct   2719  
               
               
                   
               
               
                 agattacccc ctcattgttt attaacaaat tatgttacat ctgttttaaa tttatttcaa   2779  
               
               
                   
               
               
                 aaagggaaac tattgtcccc tagcaaggca tgatgttaac cagaataaag ttctgagtgt   2839  
               
               
                   
               
               
                 ttttactaca gttgtttttt gaaaacatgg tagaattgga gagtaaaaac tgaatggaag   2899  
               
               
                   
               
               
                 gtttgtatat tgtcagatat tttttcagaa atatgtggtt tccacgatga aaaacttcca   2959  
               
               
                   
               
               
                 tgaggccaaa cgttttgaac taataaaagc ataaatgcaa acacacaaag gtataatttt   3019  
               
               
                   
               
               
                 atgaatgtct ttgttggaaa agaatacaga aagatggatg tgctttgcat tcctacaaag   3079  
               
               
                   
               
               
                 atgtttgtca gatgtgatat gtaaacataa ttcttgtata ttatggaaga ttttaaattc   3139  
               
               
                   
               
               
                 acaatagaaa ctcaccatgt aaaagagtca tctggtagat ttttaacgaa tgaagatgtc   3199  
               
               
                   
               
               
                 taatagttat tccctatttg ttttcttctg tatgttaggg tgctctggaa gagaggaatg   3259  
               
               
                   
               
               
                 cctgtgtgag caagcattta tgtttattta taagcagatt taacaattcc aaaggaatct   3319  
               
               
                   
               
               
                 ccagttttca gttgatcact ggcaatgaaa aattctcagt cagtaattgc caaagctgct   3379  
               
               
                   
               
               
                 ctagccttga ggagtgtgag aatcaaaact ctcctacact tccattaact tagcatgtgt   3439  
               
               
                   
               
               
                 tgaaaaaaaa agtttcagag aagttctggc tgaacactgg caacgacaaa gccaacagtc   3499  
               
               
                   
               
               
                 aaaacagaga tgtgataagg atcagaacag cagaggttct tttaaagggg cagaaaaact   3559  
               
               
                   
               
               
                 ctgggaaata agagagaaca actactgtga tcaggctatg tatggaatac agtgttattt   3619  
               
               
                   
               
               
                 tctttgaaat tgtttaagtg ttgtaaatat ttatgtaaac tgcattagaa attagctgtg   3679  
               
               
                   
               
               
                 tgaaatacca gtgtggtttg tgtttgagtt ttattgagaa ttttaaatta taacttaaaa   3739  
               
               
                   
               
               
                 tattttataa tttttaaagt atatatttat ttaagcttat gtcagaccta tttgacataa   3799  
               
               
                   
               
               
                 cactataaag gttgacaata aatgtgctta tgttt                              3834  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 36  
               
               
                 &lt;211&gt; LENGTH: 610  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 36  
               
               
                   
               
               
                 Met Ile Ala Ser Gln Phe Leu Ser Ala Leu Thr Leu Val Leu Leu Ile  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Lys Glu Ser Gly Ala Trp Ser Tyr Asn Thr Ser Thr Glu Ala Met Thr  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Tyr Asp Glu Ala Ser Ala Tyr Cys Gln Gln Arg Tyr Thr His Leu Val  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ala Ile Gln Asn Lys Glu Glu Ile Glu Tyr Leu Asn Ser Ile Leu Ser  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Tyr Ser Pro Ser Tyr Tyr Trp Ile Gly Ile Arg Lys Val Asn Asn Val  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Trp Val Trp Val Gly Thr Gln Lys Pro Leu Thr Glu Glu Ala Lys Asn  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Trp Ala Pro Gly Glu Pro Asn Asn Arg Gln Lys Asp Glu Asp Cys Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Glu Ile Tyr Ile Lys Arg Glu Lys Asp Val Gly Met Trp Asn Asp Glu  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Cys Ser Lys Lys Lys Leu Ala Leu Cys Tyr Thr Ala Ala Cys Thr  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Asn Thr Ser Cys Ser Gly His Gly Glu Cys Val Glu Thr Ile Asn Asn  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Tyr Thr Cys Lys Cys Asp Pro Gly Phe Ser Gly Leu Lys Cys Glu Gln  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Ile Val Asn Cys Thr Ala Leu Glu Ser Pro Glu His Gly Ser Leu Val  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Cys Ser His Pro Leu Gly Asn Phe Ser Tyr Asn Ser Ser Cys Ser Ile  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ser Cys Asp Arg Gly Tyr Leu Pro Ser Ser Met Glu Thr Met Gln Cys  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Met Ser Ser Gly Glu Trp Ser Ala Pro Ile Pro Ala Cys Asn Val Val  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Glu Cys Asp Ala Val Thr Asn Pro Ala Asn Gly Phe Val Glu Cys Phe  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Gln Asn Pro Gly Ser Phe Pro Trp Asn Thr Thr Cys Thr Phe Asp Cys  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Glu Glu Gly Phe Glu Leu Met Gly Ala Gln Ser Leu Gln Cys Thr Ser  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Ser Gly Asn Trp Asp Asn Glu Lys Pro Thr Cys Lys Ala Val Thr Cys  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Arg Ala Val Arg Gln Pro Gln Asn Gly Ser Val Arg Cys Ser His Ser  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Pro Ala Gly Glu Phe Thr Phe Lys Ser Ser Cys Asn Phe Thr Cys Glu  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Glu Gly Phe Met Leu Gln Gly Pro Ala Gln Val Glu Cys Thr Thr Gln  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Gly Gln Trp Thr Gln Gln Ile Pro Val Cys Glu Ala Phe Gln Cys Thr  
               
               
                         355                 360                 365  
               
               
                   
               
               
                 Ala Leu Ser Asn Pro Glu Arg Gly Tyr Met Asn Cys Leu Pro Ser Ala  
               
               
                     370                 375                 380  
               
               
                   
               
               
                 Ser Gly Ser Phe Arg Tyr Gly Ser Ser Cys Glu Phe Ser Cys Glu Gln  
               
               
                 385                 390                 395                 400  
               
               
                   
               
               
                 Gly Phe Val Leu Lys Gly Ser Lys Arg Leu Gln Cys Gly Pro Thr Gly  
               
               
                                 405                 410                 415  
               
               
                   
               
               
                 Glu Trp Asp Asn Glu Lys Pro Thr Cys Glu Ala Val Arg Cys Asp Ala  
               
               
                             420                 425                 430  
               
               
                   
               
               
                 Val His Gln Pro Pro Lys Gly Leu Val Arg Cys Ala His Ser Pro Ile  
               
               
                         435                 440                 445  
               
               
                   
               
               
                 Gly Glu Phe Thr Tyr Lys Ser Ser Cys Ala Phe Ser Cys Glu Glu Gly  
               
               
                     450                 455                 460  
               
               
                   
               
               
                 Phe Glu Leu Tyr Gly Ser Thr Gln Leu Glu Cys Thr Ser Gln Gly Gln  
               
               
                 465                 470                 475                 480  
               
               
                   
               
               
                 Trp Thr Glu Glu Val Pro Ser Cys Gln Val Val Lys Cys Ser Ser Leu  
               
               
                                 485                 490                 495  
               
               
                   
               
               
                 Ala Val Pro Gly Lys Ile Asn Met Ser Cys Ser Gly Glu Pro Val Phe  
               
               
                             500                 505                 510  
               
               
                   
               
               
                 Gly Thr Val Cys Lys Phe Ala Cys Pro Glu Gly Trp Thr Leu Asn Gly  
               
               
                         515                 520                 525  
               
               
                   
               
               
                 Ser Ala Ala Arg Thr Cys Gly Ala Thr Gly His Trp Ser Gly Leu Leu  
               
               
                     530                 535                 540  
               
               
                   
               
               
                 Pro Thr Cys Glu Ala Pro Thr Glu Ser Asn Ile Pro Leu Val Ala Gly  
               
               
                 545                 550                 555                 560  
               
               
                   
               
               
                 Leu Ser Ala Ala Gly Leu Ser Leu Leu Thr Leu Ala Pro Phe Leu Leu  
               
               
                                 565                 570                 575  
               
               
                   
               
               
                 Trp Leu Arg Lys Cys Leu Arg Lys Ala Lys Lys Phe Val Pro Ala Ser  
               
               
                             580                 585                 590  
               
               
                   
               
               
                 Ser Cys Gln Ser Leu Glu Ser Asp Gly Ser Tyr Gln Lys Pro Ser Tyr  
               
               
                         595                 600                 605  
               
               
                   
               
               
                 Ile Leu  
               
               
                     610  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 37  
               
               
                 &lt;211&gt; LENGTH: 1922  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (406)...(1428)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding nucleotide binding  
               
               
                       protein (G Protein), beta polypeptide 3 (GNB3)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 37  
               
               
                   
               
               
                 ccacaatagg ggcagacctg tccatccttc tctgtgggtc ccctgtacct ttctccccca     60  
               
               
                   
               
               
                 acaggatcag acccagaggc agctggttgg ggtttgtcga gaagaaggat tatccagatc    120  
               
               
                   
               
               
                 agtcctttct aatctcagct cctgcctgta ccctcccata ctcaccaaac cctcttcccc    180  
               
               
                   
               
               
                 accaccctga gctgaggagc acagtttgag gcccccccaa ccccccgccg gtcggggcca    240  
               
               
                   
               
               
                 ggccaggcca ggccagctcc tctggcagca gagcctgggc aggtgacggg cgggcgcggg    300  
               
               
                   
               
               
                 cgtcgcagct gagggagtaa ggaggctccc aggaaccgga gctggaaacc cggccgaggt    360  
               
               
                   
               
               
                 ccagccagag cccaagagcc agagtgaccc ctcgacctgt cagcc atg ggg gag atg    417  
               
               
                                                                   Met Gly Glu Met  
               
               
                                                                    1  
               
               
                   
               
               
                 gag caa ctg cgt cag gaa gcg gag cag ctc aag aag cag att gca gat      465  
               
               
                 Glu Gln Leu Arg Gln Glu Ala Glu Gln Leu Lys Lys Gln Ile Ala Asp  
               
               
                  5                   10                  15                  20  
               
               
                   
               
               
                 gcc agg aaa gcc tgt gct gac gtt act ctg gca gag ctg gtg tct ggc      513  
               
               
                 Ala Arg Lys Ala Cys Ala Asp Val Thr Leu Ala Glu Leu Val Ser Gly  
               
               
                                  25                  30                  35  
               
               
                   
               
               
                 cta gag gtg gtg gga cga gtc cag atg cgg acg cgg cgg acg tta agg      561  
               
               
                 Leu Glu Val Val Gly Arg Val Gln Met Arg Thr Arg Arg Thr Leu Arg  
               
               
                              40                  45                  50  
               
               
                   
               
               
                 gga cac ctg gcc aag att tac gcc atg cac tgg gcc act gat tct aag      609  
               
               
                 Gly His Leu Ala Lys Ile Tyr Ala Met His Trp Ala Thr Asp Ser Lys  
               
               
                          55                  60                  65  
               
               
                   
               
               
                 ctg ctg gta agt gcc tcg caa gat ggg aag ctg atc gtg tgg gac agc      657  
               
               
                 Leu Leu Val Ser Ala Ser Gln Asp Gly Lys Leu Ile Val Trp Asp Ser  
               
               
                      70                  75                  80  
               
               
                   
               
               
                 tac acc acc aac aag gtg cac gcc atc cca ctg cgc tcc tcc tgg gtc      705  
               
               
                 Tyr Thr Thr Asn Lys Val His Ala Ile Pro Leu Arg Ser Ser Trp Val  
               
               
                  85                  90                  95                 100  
               
               
                   
               
               
                 atg acc tgt gcc tat gcc cca tca ggg aac ttt gtg gca tgt ggg ggg      753  
               
               
                 Met Thr Cys Ala Tyr Ala Pro Ser Gly Asn Phe Val Ala Cys Gly Gly  
               
               
                                 105                 110                 115  
               
               
                   
               
               
                 ctg gac aac atg tgt tcc atc tac aac ctc aaa tcc cgt gag ggc aat      801  
               
               
                 Leu Asp Asn Met Cys Ser Ile Tyr Asn Leu Lys Ser Arg Glu Gly Asn  
               
               
                             120                 125                 130  
               
               
                   
               
               
                 gtc aag gtc agc cgg gag ctt tct gct cac aca ggt tat ctc tcc tgc      849  
               
               
                 Val Lys Val Ser Arg Glu Leu Ser Ala His Thr Gly Tyr Leu Ser Cys  
               
               
                         135                 140                 145  
               
               
                   
               
               
                 tgc cgc ttc ctg gat gac aac aat att gtg acc agc tcg ggg gac acc      897  
               
               
                 Cys Arg Phe Leu Asp Asp Asn Asn Ile Val Thr Ser Ser Gly Asp Thr  
               
               
                     150                 155                 160  
               
               
                   
               
               
                 acg tgt gcc ttg tgg gac att gag act ggg cag cag aag act gta ttt      945  
               
               
                 Thr Cys Ala Leu Trp Asp Ile Glu Thr Gly Gln Gln Lys Thr Val Phe  
               
               
                 165                 170                 175                 180  
               
               
                   
               
               
                 gtg gga cac acg ggt gac tgc atg agc ctg gct gtg tct cct gac ttc      993  
               
               
                 Val Gly His Thr Gly Asp Cys Met Ser Leu Ala Val Ser Pro Asp Phe  
               
               
                                 185                 190                 195  
               
               
                   
               
               
                 aat ctc ttc att tcg ggg gcc tgt gat gcc agt gcc aag ctc tgg gat     1041  
               
               
                 Asn Leu Phe Ile Ser Gly Ala Cys Asp Ala Ser Ala Lys Leu Trp Asp  
               
               
                             200                 205                 210  
               
               
                   
               
               
                 gtg cga gag ggg acc tgc cgt cag act ttc act ggc cac gag tcg gac     1089  
               
               
                 Val Arg Glu Gly Thr Cys Arg Gln Thr Phe Thr Gly His Glu Ser Asp  
               
               
                         215                 220                 225  
               
               
                   
               
               
                 atc aac gcc atc tgt ttc ttc ccc aat gga gag gcc atc tgc acg ggc     1137  
               
               
                 Ile Asn Ala Ile Cys Phe Phe Pro Asn Gly Glu Ala Ile Cys Thr Gly  
               
               
                     230                 235                 240  
               
               
                   
               
               
                 tcg gat gac gct tcc tgc cgc ttg ttt gac ctg cgg gca gac cag gag     1185  
               
               
                 Ser Asp Asp Ala Ser Cys Arg Leu Phe Asp Leu Arg Ala Asp Gln Glu  
               
               
                 245                 250                 255                 260  
               
               
                   
               
               
                 ctg atc tgc ttc tcc cac gag agc atc atc tgc ggc atc acg tcc gtg     1233  
               
               
                 Leu Ile Cys Phe Ser His Glu Ser Ile Ile Cys Gly Ile Thr Ser Val  
               
               
                                 265                 270                 275  
               
               
                   
               
               
                 gcc ttc tcc ctc agt ggc cgc cta cta ttc gct ggc tac gac gac ttc     1281  
               
               
                 Ala Phe Ser Leu Ser Gly Arg Leu Leu Phe Ala Gly Tyr Asp Asp Phe  
               
               
                             280                 285                 290  
               
               
                   
               
               
                 aac tgc aat gtc tgg gac tcc atg aag tct gag cgt gtg ggc atc ctc     1329  
               
               
                 Asn Cys Asn Val Trp Asp Ser Met Lys Ser Glu Arg Val Gly Ile Leu  
               
               
                         295                 300                 305  
               
               
                   
               
               
                 tct ggc cac gat aac agg gtg agc tgc ctg gga gtc aca gct gac ggg     1377  
               
               
                 Ser Gly His Asp Asn Arg Val Ser Cys Leu Gly Val Thr Ala Asp Gly  
               
               
                     310                 315                 320  
               
               
                   
               
               
                 atg gct gtg gcc aca ggt tcc tgg gac agc ttc ctc aaa atc tgg aac     1425  
               
               
                 Met Ala Val Ala Thr Gly Ser Trp Asp Ser Phe Leu Lys Ile Trp Asn  
               
               
                 325                 330                 335                 340  
               
               
                   
               
               
                 tga ggaggctgga gaaagggaag tggaaggcag tgaacacact cagcagcccc          1478  
               
               
                   
               
               
                 ctgcccgacc ccatctcatt caggtgttct cttctatatt ccgggtgcca ttcccactaa   1538  
               
               
                   
               
               
                 gctttctcct ttgagggcag tggggagcat gggactgtgc ctttgggagg cagcatcagg   1598  
               
               
                   
               
               
                 gacacagggg caaagaactg ccccatctcc tcccatggcc ttccctcccc acagtcctca   1658  
               
               
                   
               
               
                 cagcctctcc cttaatgagc aaggacaacc tgcccctccc cagccctttg caggcccagc   1718  
               
               
                   
               
               
                 agacttgagt ctgaggcccc aggccctagg attcctcccc cagagccact acctttgtcc   1778  
               
               
                   
               
               
                 aggcctgggt ggtatagggc gtttggccct gtgactatgg ctctggcacc actagggtcc   1838  
               
               
                   
               
               
                 tggccctctt cttattcatg ctttctcctt tttctacctt tttttctctc ctaagacacc   1898  
               
               
                   
               
               
                 tgcaataaag tgtagcaccc tggt                                          1922  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 38  
               
               
                 &lt;211&gt; LENGTH: 340  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 38  
               
               
                   
               
               
                 Met Gly Glu Met Glu Gln Leu Arg Gln Glu Ala Glu Gln Leu Lys Lys  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gln Ile Ala Asp Ala Arg Lys Ala Cys Ala Asp Val Thr Leu Ala Glu  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Leu Val Ser Gly Leu Glu Val Val Gly Arg Val Gln Met Arg Thr Arg  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Arg Thr Leu Arg Gly His Leu Ala Lys Ile Tyr Ala Met His Trp Ala  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Thr Asp Ser Lys Leu Leu Val Ser Ala Ser Gln Asp Gly Lys Leu Ile  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Val Trp Asp Ser Tyr Thr Thr Asn Lys Val His Ala Ile Pro Leu Arg  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Ser Ser Trp Val Met Thr Cys Ala Tyr Ala Pro Ser Gly Asn Phe Val  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Ala Cys Gly Gly Leu Asp Asn Met Cys Ser Ile Tyr Asn Leu Lys Ser  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Arg Glu Gly Asn Val Lys Val Ser Arg Glu Leu Ser Ala His Thr Gly  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Tyr Leu Ser Cys Cys Arg Phe Leu Asp Asp Asn Asn Ile Val Thr Ser  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ser Gly Asp Thr Thr Cys Ala Leu Trp Asp Ile Glu Thr Gly Gln Gln  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Lys Thr Val Phe Val Gly His Thr Gly Asp Cys Met Ser Leu Ala Val  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Ser Pro Asp Phe Asn Leu Phe Ile Ser Gly Ala Cys Asp Ala Ser Ala  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Lys Leu Trp Asp Val Arg Glu Gly Thr Cys Arg Gln Thr Phe Thr Gly  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 His Glu Ser Asp Ile Asn Ala Ile Cys Phe Phe Pro Asn Gly Glu Ala  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Ile Cys Thr Gly Ser Asp Asp Ala Ser Cys Arg Leu Phe Asp Leu Arg  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Ala Asp Gln Glu Leu Ile Cys Phe Ser His Glu Ser Ile Ile Cys Gly  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 Ile Thr Ser Val Ala Phe Ser Leu Ser Gly Arg Leu Leu Phe Ala Gly  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Tyr Asp Asp Phe Asn Cys Asn Val Trp Asp Ser Met Lys Ser Glu Arg  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Val Gly Ile Leu Ser Gly His Asp Asn Arg Val Ser Cys Leu Gly Val  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Thr Ala Asp Gly Met Ala Val Ala Thr Gly Ser Trp Asp Ser Phe Leu  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Lys Ile Trp Asn  
               
               
                             340  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 39  
               
               
                 &lt;211&gt; LENGTH: 2443  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;221&gt; NAME/KEY: CDS  
               
               
                 &lt;222&gt; LOCATION: (162)...(1253)  
               
               
                 &lt;223&gt; OTHER INFORMATION: Nucleotide sequence encoding angiotensin  
               
               
                       receptor 2  (AGTR2)  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 39  
               
               
                   
               
               
                 acgtcccagc gtctgagaga acgagtaagc aagaattcaa agcattctgc agcctgaatt     60  
               
               
                   
               
               
                 ttgaaggagt gtgtttaggc actaagcaag ctgatttatg ataactgctt taaacttcaa    120  
               
               
                   
               
               
                 caaccaaagg cataagaact aggagctgct gacatttcaa t atg aag ggc aac tcc    176  
               
               
                                                               Met Lys Gly Asn Ser  
               
               
                                                                1               5  
               
               
                   
               
               
                 acc ctt gcc act act agc aaa aac att acc agc ggt ctt cac ttc ggg      224  
               
               
                 Thr Leu Ala Thr Thr Ser Lys Asn Ile Thr Ser Gly Leu His Phe Gly  
               
               
                                  10                  15                  20  
               
               
                   
               
               
                 ctt gtg aac atc tct ggc aac aat gag tct acc ttg aac tgt tca cag      272  
               
               
                 Leu Val Asn Ile Ser Gly Asn Asn Glu Ser Thr Leu Asn Cys Ser Gln  
               
               
                              25                  30                  35  
               
               
                   
               
               
                 aaa cca tca gat aag cat tta gat gca att cct att ctt tac tac att      320  
               
               
                 Lys Pro Ser Asp Lys His Leu Asp Ala Ile Pro Ile Leu Tyr Tyr Ile  
               
               
                          40                  45                  50  
               
               
                   
               
               
                 ata ttt gta att gga ttt ctg gtc aat att gtc gtg gtt aca ctg ttt      368  
               
               
                 Ile Phe Val Ile Gly Phe Leu Val Asn Ile Val Val Val Thr Leu Phe  
               
               
                      55                  60                  65  
               
               
                   
               
               
                 tgt tgt caa aag ggt cct aaa aag gtt tct agc ata tac atc ttc aac      416  
               
               
                 Cys Cys Gln Lys Gly Pro Lys Lys Val Ser Ser Ile Tyr Ile Phe Asn  
               
               
                  70                  75                  80                  85  
               
               
                   
               
               
                 ctc gct gtg gct gat tta ctc ctt ttg gct act ctt cct cta tgg gca      464  
               
               
                 Leu Ala Val Ala Asp Leu Leu Leu Leu Ala Thr Leu Pro Leu Trp Ala  
               
               
                                  90                  95                 100  
               
               
                   
               
               
                 acc tat tat tct tat aga tat gac tgg ctc ttt gga cct gtg atg tgc      512  
               
               
                 Thr Tyr Tyr Ser Tyr Arg Tyr Asp Trp Leu Phe Gly Pro Val Met Cys  
               
               
                             105                 110                 115  
               
               
                   
               
               
                 aaa gtt ttt ggt tct ttt ctt acc ctg aac atg ttt gca agc att ttt      560  
               
               
                 Lys Val Phe Gly Ser Phe Leu Thr Leu Asn Met Phe Ala Ser Ile Phe  
               
               
                         120                 125                 130  
               
               
                   
               
               
                 ttt atc acc tgc atg agt gtt gat agg tac caa tct gtc atc tac ccc      608  
               
               
                 Phe Ile Thr Cys Met Ser Val Asp Arg Tyr Gln Ser Val Ile Tyr Pro  
               
               
                     135                 140                 145  
               
               
                   
               
               
                 ttt ctg tct caa aga aga aat ccc tgg caa gca tct tat ata gtt ccc      656  
               
               
                 Phe Leu Ser Gln Arg Arg Asn Pro Trp Gln Ala Ser Tyr Ile Val Pro  
               
               
                 150                 155                 160                 165  
               
               
                   
               
               
                 ctt gtt tgg tgt atg gcc tgt ttg tcc tca ttg cca aca ttt tat ttt      704  
               
               
                 Leu Val Trp Cys Met Ala Cys Leu Ser Ser Leu Pro Thr Phe Tyr Phe  
               
               
                                 170                 175                 180  
               
               
                   
               
               
                 cga gac gtc aga acc att gaa tac tta gga gtg aat gct tgc att atg      752  
               
               
                 Arg Asp Val Arg Thr Ile Glu Tyr Leu Gly Val Asn Ala Cys Ile Met  
               
               
                             185                 190                 195  
               
               
                   
               
               
                 gct ttc cca cct gag aaa tat gcc caa tgg tca gct ggg att gcc tta      800  
               
               
                 Ala Phe Pro Pro Glu Lys Tyr Ala Gln Trp Ser Ala Gly Ile Ala Leu  
               
               
                         200                 205                 210  
               
               
                   
               
               
                 atg aaa aat atc ctt ggt ttt att atc cct tta ata ttc ata gca aca      848  
               
               
                 Met Lys Asn Ile Leu Gly Phe Ile Ile Pro Leu Ile Phe Ile Ala Thr  
               
               
                     215                 220                 225  
               
               
                   
               
               
                 tgc tat ttt gga att aga aaa cac tta ctg aag acg aat agc tat ggg      896  
               
               
                 Cys Tyr Phe Gly Ile Arg Lys His Leu Leu Lys Thr Asn Ser Tyr Gly  
               
               
                 230                 235                 240                 245  
               
               
                   
               
               
                 aag aac agg ata acc cgt gac caa gtc ctg aag atg gca gct gct gtt      944  
               
               
                 Lys Asn Arg Ile Thr Arg Asp Gln Val Leu Lys Met Ala Ala Ala Val  
               
               
                                 250                 255                 260  
               
               
                   
               
               
                 gtt ctg gcc ttc atc att tgg tgc ctt ccc ttc cat gtt ctg acc ttc      992  
               
               
                 Val Leu Ala Phe Ile Ile Trp Cys Leu Pro Phe His Val Leu Thr Phe  
               
               
                             265                 270                 275  
               
               
                   
               
               
                 ctg gat gct ctg gcc tgg atg ggt gtc att aat agc tgc gaa gtt ata     1040  
               
               
                 Leu Asp Ala Leu Ala Trp Met Gly Val Ile Asn Ser Cys Glu Val Ile  
               
               
                         280                 285                 290  
               
               
                   
               
               
                 gca gtc att gac ctg gca ctt cct ttt gcc atc ctc ttg gga ttc acc     1088  
               
               
                 Ala Val Ile Asp Leu Ala Leu Pro Phe Ala Ile Leu Leu Gly Phe Thr  
               
               
                     295                 300                 305  
               
               
                   
               
               
                 aac agc tgc gtt aat ccg ttt ctg tat tgt ttt gtt gga aac cgg ttc     1136  
               
               
                 Asn Ser Cys Val Asn Pro Phe Leu Tyr Cys Phe Val Gly Asn Arg Phe  
               
               
                 310                 315                 320                 325  
               
               
                   
               
               
                 caa cag aag ctc cgc agt gtg ttt agg gtt cca att act tgg ctc caa     1184  
               
               
                 Gln Gln Lys Leu Arg Ser Val Phe Arg Val Pro Ile Thr Trp Leu Gln  
               
               
                                 330                 335                 340  
               
               
                   
               
               
                 ggg aaa aga gag agt atg tct tgc cgg aaa agc agt tct ctt aga gaa     1232  
               
               
                 Gly Lys Arg Glu Ser Met Ser Cys Arg Lys Ser Ser Ser Leu Arg Glu  
               
               
                             345                 350                 355  
               
               
                   
               
               
                 atg gag acc ttt gtg tct taa acggagagca aaatgcatgt aatcaacatg        1283  
               
               
                 Met Glu Thr Phe Val Ser  *  
               
               
                         360  
               
               
                   
               
               
                 gctacttgct ttgaggctca ccagaattat ttttaagtgg ttttaataaa ataataaaat   1343  
               
               
                   
               
               
                 ttcccctaat cttttctgaa tcttctgaaa ccaaatgtaa ctatgtttat cgtccagtga   1403  
               
               
                   
               
               
                 ctttcaggaa tgcccattgt tttctgatat gtttgtacaa gatttcattg gtgagacata   1463  
               
               
                   
               
               
                 tttacaacct agaagtaact ggtgatatat ctcaaattgt aattaataat agattgtgaa   1523  
               
               
                   
               
               
                 taatgatttg gggattcaga tttctctttg aaacatgctt gtgtttctta gtggggtttt   1583  
               
               
                   
               
               
                 atatccattt ttatcaggat ttcctcttga accagaacca gtctttcaac tcattgcatc   1643  
               
               
                   
               
               
                 atttacaaga caacattgta agagagatga gcacttctaa gttgagtata ttataataga   1703  
               
               
                   
               
               
                 ttagtactgg attattcagg ctttaggcat atgcttcttt aaaaacgcta taaattatat   1763  
               
               
                   
               
               
                 tcctcttgca tttcacttga gtggaggttt atagttaatc tataactaca tattgaatag   1823  
               
               
                   
               
               
                 ggctaggaat atagattaaa tcatactcct atgctttagc ttatttttac agttatagaa   1883  
               
               
                   
               
               
                 agcaagatgt actataacat agaattgcaa tctataatat ttgtgtgttc actaaactct   1943  
               
               
                   
               
               
                 gaataagcac tttttaaaaa actttctact cattttaatg attgtttaaa ggtttctatt   2003  
               
               
                   
               
               
                 ttctctgata cttttttgaa atcagtaaac actgtgtatt gttgtaaaat gtaaaggtca   2063  
               
               
                   
               
               
                 cttttcacat ccttgacttt ttagatgtgc tgctttgata tataggacat tgatttgatt   2123  
               
               
                   
               
               
                 tttattatta atgctttggt tctgggttgt ttcctaaaat atctgggtgg cttaaaaaaa   2183  
               
               
                   
               
               
                 actctttaac ttgtaataaa cccttaactg gcataggaaa tggtatccag aatggaattt   2243  
               
               
                   
               
               
                 tgctacatgg ggtctgggtg ggggcaaaga gacccagtca attacatgtt tggtaccaag   2303  
               
               
                   
               
               
                 aaaggaacct gtcagggcag tacaatgtga ctttgaaaat atataccgtg ggggtagttt   2363  
               
               
                   
               
               
                 taccctatat ctataaacac tgtttgttcc agaatctgta tgattctatg gagctatttt   2423  
               
               
                   
               
               
                 aaaccaattg caggtctaga                                               2443  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 40  
               
               
                 &lt;211&gt; LENGTH: 363  
               
               
                 &lt;212&gt; TYPE: PRT  
               
               
                 &lt;213&gt; ORGANISM: Homo sapien  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 40  
               
               
                   
               
               
                 Met Lys Gly Asn Ser Thr Leu Ala Thr Thr Ser Lys Asn Ile Thr Ser  
               
               
                  1               5                  10                  15  
               
               
                   
               
               
                 Gly Leu His Phe Gly Leu Val Asn Ile Ser Gly Asn Asn Glu Ser Thr  
               
               
                             20                  25                  30  
               
               
                   
               
               
                 Leu Asn Cys Ser Gln Lys Pro Ser Asp Lys His Leu Asp Ala Ile Pro  
               
               
                         35                  40                  45  
               
               
                   
               
               
                 Ile Leu Tyr Tyr Ile Ile Phe Val Ile Gly Phe Leu Val Asn Ile Val  
               
               
                     50                  55                  60  
               
               
                   
               
               
                 Val Val Thr Leu Phe Cys Cys Gln Lys Gly Pro Lys Lys Val Ser Ser  
               
               
                 65                  70                  75                  80  
               
               
                   
               
               
                 Ile Tyr Ile Phe Asn Leu Ala Val Ala Asp Leu Leu Leu Leu Ala Thr  
               
               
                                 85                  90                  95  
               
               
                   
               
               
                 Leu Pro Leu Trp Ala Thr Tyr Tyr Ser Tyr Arg Tyr Asp Trp Leu Phe  
               
               
                             100                 105                 110  
               
               
                   
               
               
                 Gly Pro Val Met Cys Lys Val Phe Gly Ser Phe Leu Thr Leu Asn Met  
               
               
                         115                 120                 125  
               
               
                   
               
               
                 Phe Ala Ser Ile Phe Phe Ile Thr Cys Met Ser Val Asp Arg Tyr Gln  
               
               
                     130                 135                 140  
               
               
                   
               
               
                 Ser Val Ile Tyr Pro Phe Leu Ser Gln Arg Arg Asn Pro Trp Gln Ala  
               
               
                 145                 150                 155                 160  
               
               
                   
               
               
                 Ser Tyr Ile Val Pro Leu Val Trp Cys Met Ala Cys Leu Ser Ser Leu  
               
               
                                 165                 170                 175  
               
               
                   
               
               
                 Pro Thr Phe Tyr Phe Arg Asp Val Arg Thr Ile Glu Tyr Leu Gly Val  
               
               
                             180                 185                 190  
               
               
                   
               
               
                 Asn Ala Cys Ile Met Ala Phe Pro Pro Glu Lys Tyr Ala Gln Trp Ser  
               
               
                         195                 200                 205  
               
               
                   
               
               
                 Ala Gly Ile Ala Leu Met Lys Asn Ile Leu Gly Phe Ile Ile Pro Leu  
               
               
                     210                 215                 220  
               
               
                   
               
               
                 Ile Phe Ile Ala Thr Cys Tyr Phe Gly Ile Arg Lys His Leu Leu Lys  
               
               
                 225                 230                 235                 240  
               
               
                   
               
               
                 Thr Asn Ser Tyr Gly Lys Asn Arg Ile Thr Arg Asp Gln Val Leu Lys  
               
               
                                 245                 250                 255  
               
               
                   
               
               
                 Met Ala Ala Ala Val Val Leu Ala Phe Ile Ile Trp Cys Leu Pro Phe  
               
               
                             260                 265                 270  
               
               
                   
               
               
                 His Val Leu Thr Phe Leu Asp Ala Leu Ala Trp Met Gly Val Ile Asn  
               
               
                         275                 280                 285  
               
               
                   
               
               
                 Ser Cys Glu Val Ile Ala Val Ile Asp Leu Ala Leu Pro Phe Ala Ile  
               
               
                     290                 295                 300  
               
               
                   
               
               
                 Leu Leu Gly Phe Thr Asn Ser Cys Val Asn Pro Phe Leu Tyr Cys Phe  
               
               
                 305                 310                 315                 320  
               
               
                   
               
               
                 Val Gly Asn Arg Phe Gln Gln Lys Leu Arg Ser Val Phe Arg Val Pro  
               
               
                                 325                 330                 335  
               
               
                   
               
               
                 Ile Thr Trp Leu Gln Gly Lys Arg Glu Ser Met Ser Cys Arg Lys Ser  
               
               
                             340                 345                 350  
               
               
                   
               
               
                 Ser Ser Leu Arg Glu Met Glu Thr Phe Val Ser  
               
               
                         355                 360  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 41  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 41  
               
               
                   
               
               
                 actgcctgat aaccatgctg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 42  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 42  
               
               
                   
               
               
                 atacttacac accaggaggg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 43  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 43  
               
               
                   
               
               
                 atgcctgctc caaaggcac                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 44  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 44  
               
               
                   
               
               
                 atgcctgctc caaaggcacc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 45  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 45  
               
               
                   
               
               
                 atgcctgctc caaaggcaca t                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 46  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 46  
               
               
                   
               
               
                 tacttctggt tctctgagcg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 47  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 47  
               
               
                   
               
               
                 actcaccttg aactcgtctc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 48  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 48  
               
               
                   
               
               
                 tggttctctg agcgagtctt                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 49  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 49  
               
               
                   
               
               
                 tggttctctg agcgagtctt c                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 50  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 50  
               
               
                   
               
               
                 tggttctctg agcgagtctt tc                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 51  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 51  
               
               
                   
               
               
                 tgcagatgga ctttggcttc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 52  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 52  
               
               
                   
               
               
                 tgcttgcctt ctgctacaag                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 53  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 53  
               
               
                   
               
               
                 cttccctgag cacctgctg                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 54  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 54  
               
               
                   
               
               
                 cttccctgag cacctgctgg t                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 55  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 55  
               
               
                   
               
               
                 cttccctgag cacctgctga                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 56  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 56  
               
               
                   
               
               
                 aacagctcag gacgaaactg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 57  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 57  
               
               
                   
               
               
                 agaaggagtt gaccttgtcc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 58  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 58  
               
               
                   
               
               
                 ggaagctcaa gtggccttc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 59  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 59  
               
               
                   
               
               
                 ggaagctcaa gtggccttcc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 60  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 60  
               
               
                   
               
               
                 ggaagctcaa gtggccttca ac                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 61  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 61  
               
               
                   
               
               
                 aagtcactgg cagagctgg                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 62  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 62  
               
               
                   
               
               
                 gcaccagggc tttgttgaag                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 63  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 63  
               
               
                   
               
               
                 ttttccccgt agggctcca                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 64  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 64  
               
               
                   
               
               
                 ttttccccgt agggctccac                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 65  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 65  
               
               
                   
               
               
                 ttttccccgt agggctccag c                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 66  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 66  
               
               
                   
               
               
                 tgcagaagtc actggcagag                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 67  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 67  
               
               
                   
               
               
                 gttgaagttt tccccgtagg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 68  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 68  
               
               
                   
               
               
                 actcctccac ctgctggtc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 69  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 69  
               
               
                   
               
               
                 actcctccac ctgctggtcc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 70  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 70  
               
               
                   
               
               
                 actcctccac ctgctggtct a                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 71  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 71  
               
               
                   
               
               
                 aggacgtgcg tggcaacctg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 72  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 72  
               
               
                   
               
               
                 agctctgcca gtgacttctg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 73  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 73  
               
               
                   
               
               
                 gtgacttctg cagcccctc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 74  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artitifical sequence  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 74  
               
               
                   
               
               
                 gtgacttctg cagcccctca                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 75  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 75  
               
               
                   
               
               
                 gtgacttctg cagcccctcg gt                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 76  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 76  
               
               
                   
               
               
                 cctgaccttc cagatgaag                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 77  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 77  
               
               
                   
               
               
                 tcaggttgcc acgcacgtc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 78  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 78  
               
               
                   
               
               
                 caggatctcg gccagtgc                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 79  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 79  
               
               
                   
               
               
                 caggatctcg gccagtgcc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 80  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 80  
               
               
                   
               
               
                 caggatctcg gccagtgctg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 81  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 81  
               
               
                   
               
               
                 acctgcgaga gcttcagcag                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 82  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 82  
               
               
                   
               
               
                 tctccatgcg ctgtgcgtag                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 83  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 83  
               
               
                   
               
               
                 agctgcgcac ccaggtca                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 84  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 84  
               
               
                   
               
               
                 agctgcgcac ccaggtcaa                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 85  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 85  
               
               
                   
               
               
                 agctgcgcac ccaggtcagc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 86  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 86  
               
               
                   
               
               
                 tgtccaagga gctgcaggc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 87  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 87  
               
               
                   
               
               
                 cttacgcagc ttgcgcaggt                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 88  
               
               
                 &lt;211&gt; LENGTH: 18  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 88  
               
               
                   
               
               
                 gcggacatgg aggacgtg                                                   18  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 89  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 89  
               
               
                   
               
               
                 gcggacatgg aggacgtgc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 90  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 90  
               
               
                   
               
               
                 gcggacatgg aggacgtgtg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 91  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 91  
               
               
                   
               
               
                 gttgtagaaa gaaccgctgc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 92  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 92  
               
               
                   
               
               
                 gagaacgagt cttcaggtac                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 93  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 93  
               
               
                   
               
               
                 acaatctggg ctatgagatc a                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 94  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 94  
               
               
                   
               
               
                 acaatctggg ctatgagatc aa                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 95  
               
               
                 &lt;211&gt; LENGTH: 23  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 95  
               
               
                   
               
               
                 acaatctggg ctatgagatc agt                                             23  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 96  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 96  
               
               
                   
               
               
                 cactctacac tgcatgtctc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 97  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 97  
               
               
                   
               
               
                 acccttctga aaaggagagg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 98  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 98  
               
               
                   
               
               
                 gaggagagac aaggcagata                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 99  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 99  
               
               
                   
               
               
                 gaggagagac aaggcagata t                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 100  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 100  
               
               
                   
               
               
                 gaggagagac aaggcagata gt                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 101  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 101  
               
               
                   
               
               
                 aaaggttcag ttgctgctgc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 102  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 102  
               
               
                   
               
               
                 gctggggaag gtctaataac                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 103  
               
               
                 &lt;211&gt; LENGTH: 19  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 103  
               
               
                   
               
               
                 gttgctgctg cctcgaatc                                                  19  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 104  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 104  
               
               
                   
               
               
                 gttgctgctg cctcgaatcc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 105  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 105  
               
               
                   
               
               
                 gttgctgctg cctcgaatct g                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 106  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 106  
               
               
                   
               
               
                 cgtctttctc cagatgatgc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 107  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 107  
               
               
                   
               
               
                 agtgtcctat gggctgtttg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 108  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 108  
               
               
                   
               
               
                 ggatgccatt cataccttta c                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 109  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 109  
               
               
                   
               
               
                 ggatgccatt cataccttta cc                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 110  
               
               
                 &lt;211&gt; LENGTH: 23  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 110  
               
               
                   
               
               
                 ggatgccatt cataccttta cgc                                             23  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 111  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 111  
               
               
                   
               
               
                 tgggaaaaca gtgcagtgtg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 112  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 112  
               
               
                   
               
               
                 tgatcgtctt cagaacgagg                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 113  
               
               
                 &lt;211&gt; LENGTH: 23  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 113  
               
               
                   
               
               
                 ccagaccatc atcatcccat gga                                             23  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 114  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 114  
               
               
                   
               
               
                 ccagaccatc atcccatgga a                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 115  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 115  
               
               
                   
               
               
                 ccagaccatc atcccatgga gc                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 116  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 116  
               
               
                   
               
               
                 cagcaatcgt ctttctccag                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 117  
               
               
                 &lt;211&gt; LENGTH: 20  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 117  
               
               
                   
               
               
                 tcctatgggc tgtttgatgc                                                 20  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 118  
               
               
                 &lt;211&gt; LENGTH: 21  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 118  
               
               
                   
               
               
                 gtctttctcc agatgatgcc a                                               21  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 119  
               
               
                 &lt;211&gt; LENGTH: 22  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 119  
               
               
                   
               
               
                 gtctttctcc agatgatgcc aa                                              22  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 120  
               
               
                 &lt;211&gt; LENGTH: 23  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 120  
               
               
                   
               
               
                 gtctttctcc agatgatgcc agt                                             23  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 121  
               
               
                 &lt;211&gt; LENGTH: 23  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 121  
               
               
                   
               
               
                 agcggataac aatttcacac agg                                             23  
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 122  
               
               
                 &lt;211&gt; LENGTH: 16  
               
               
                 &lt;212&gt; TYPE: DNA  
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence  
               
               
                 &lt;220&gt; FEATURE:  
               
               
                 &lt;223&gt; OTHER INFORMATION: Primer  
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 122  
               
               
                   
               
               
                 ggcgcacgcc tccacg                                                     16