Patent Publication Number: US-2004053396-A1

Title: Molecules for disease detection and treatment

Description:
TECHNICAL FIELD  
       [0001] This invention relates to nucleic acid and amino acid sequences of full-length human molecules for disease detection and treatment and to the use of these sequences in the diagnosis, treatment, and prevention of developmental, cell proliferative, and immunological disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of full-length human molecules for disease detection and treatment.  
       BACKGROUND OF THE INVENTION  
       [0002] It is estimated that only 2% of mammalian DNA encodes proteins, and only a small fraction of the genes that encode proteins is actually expressed in a particular cell at any time. The various types of cells in a multicellular organism differ dramatically both in structure and function, and the identity of a particular cell is conferred by its unique pattern of gene expression. In addition, different cell types express overlapping but distinctive sets of genes throughout development. Cell growth and proliferation, cell differentiation, the immune response, apoptosis, and other processes that contribute to organism development and survival are governed by regulation of gene expression. Appropriate gene regulation also ensures that cells function efficiently by expressing only those genes whose functions are required at a given time. Factors that influence gene expression include extracellular signals that mediate cell-cell communication and coordinate the activities of different cell types. Gene expression is regulated at the level of DNA and RNA transcription, and at the level of mRNA translation.  
       [0003] Aberrant expression or mutations in genes and their products may cause, or increase susceptibility to, a variety of human diseases such as cancer and other cell proliferative disorders. The identification of these genes and their products is the basis of an ever-expanding effort to finding markers for early detection of diseases and targets for their prevention and treatment. For example, cancer represents a type of cell proliferative disorder that affects nearly every tissue in the body. The development of cancer, or oncogenesis, is often correlated with the conversion of a normal gene into a cancer-causing gene, or oncogene, through abnormal expression or mutation. Oncoproteins, the products of oncogenes, include a variety of molecules that influence cell proliferation, such as growth factors, growth factor receptors, intracellular signal transducers, nuclear transcription factors, and cell-cycle control proteins. In contrast, tumor-suppressor genes are involved in inhibiting cell proliferation. Mutations which reduce or abrogate the function of tumor-suppressor genes result in aberrant cell proliferation and cancer. Thus a wide variety of genes and their products have been found that are associated with cell proliferative disorders such as cancer, but many more may exist that are yet to be discovered.  
       [0004] DNA-based arrays can provide an efficient, high-throughput method to examine gene expression and genetic variability. For example, SNPs, or single nucleotide polymorphisms, are the most common type of human genetic variation. DNA-based arrays can dramatically accelerate the discovery of SNPs in hundreds and even thousands of genes. Likewise, such arrays can be used for SNP genotyping in which DNA samples from individuals or populations are assayed for the presence of selected SNPs. These approaches will ultimately lead to the systematic identification of all genetic variations in the human genome and the correlation of certain genetic variations with disease susceptibility, responsiveness to drug treatments, and other medically relevant information. (See, for example, Wang, D. G. et al. (1998) Science 280:1077-1082.)  
       [0005] DNA-based array technology is especially important for the rapid analysis of global gene expression patterns. For example, genetic predisposition, disease, or therapeutic treatment may directly or indirectly affect the expression of a large number of genes in a given tissue. In this case, it is useful to develop a profile, or transcript image, of all the genes that are expressed and the levels at which they are expressed in that particular tissue. A profile generated from an individual or population affected with a certain disease or undergoing a particular therapy may be compared with a profile likewise generated from a control individual or population. Such analysis does not require knowledge of gene function, as the expression profiles can subjected to mathematical analyses which simply treat each gene as a marker. Furthermore, gene expression profiles may help dissect biological pathways by identifying all the genes expressed, for example, at a certain developmental stage, in a particular tissue, or in response to disease or treatment. (See, for example, Lander, E. S. et al. (1996) Science 274:536-539.)  
       [0006] The discovery of new full-length human molecules for disease detection and treatment, and the polynucleotides encoding them, satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of developmental, cell proliferative, and immunological disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of full-length human molecules for disease detection and treatment.  
       SUMMARY OF THE INVENTION  
       [0007] The invention features purified polypeptides, full-length human molecules for disease detection and treatment, referred to collectively as “MDDT” and individually as “MDDT-1,” “MDDT-2,” “MDDT-3,” “MDDT-4,” “MDDT-5,” “MDDT-6,” “MDDT-7,” “MDDT-8,” “MDDT-9,” “MDDT-10,” “MDDT-11,” and “MDDT-12.” In one aspect, the invention provides an isolated polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1-12.  
       [0008] The invention further provides an isolated polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-12. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID NO:13-24.  
       [0009] Additionally, the invention provides a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. In one alternative, the invention provides a cell transformed with the recombinant polynucleotide. In another alternative, the invention provides a transgenic organism comprising the recombinant polynucleotide.  
       [0010] The invention also provides a method for producing a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed.  
       [0011] Additionally, the invention provides an isolated antibody which specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12.  
       [0012] The invention further provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). In one alternative, the polynucleotide comprises at least 60 contiguous nucleotides.  
       [0013] Additionally, the invention provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and optionally, if present, the amount thereof. In one alternative, the probe comprises at least 60 contiguous nucleotides.  
       [0014] The invention further provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.  
       [0015] The invention further provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and a pharmaceutically acceptable excipient. In one embodiment, the composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. The invention additionally provides a method of treating a disease or condition associated with decreased expression of functional MDDT, comprising administering to a patient in need of such treatment the composition.  
       [0016] The invention also provides a method for screening a compound for effectiveness as an agonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. In one alternative, the invention provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with decreased expression of functional MDDT, comprising administering to a patient in need of such treatment the composition.  
       [0017] Additionally, the invention provides a method for screening a compound for effectiveness as an antagonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. In one alternative, the invention provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with overexpression of functional MDDT, comprising administering to a patient in need of such treatment the composition.  
       [0018] The invention further provides a method of screening for a compound that specifically binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide.  
       [0019] The invention further provides a method of screening for a compound that modulates the activity of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-12. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide.  
       [0020] The invention further provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound.  
       [0021] The invention further provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 13-24, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:13-24, iii) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide comprises a fragment of a polynucleotide sequence selected from the group consisting of i)-v) above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.  
       Brief Description of the Tables  
       [0022] Table 1 summarizes the nomenclature for the full length polynucleotide and polypeptide sequences of the present invention.  
       [0023] Table 2 shows the GenBank identification number and annotation of the nearest GenBank homolog for polypeptides of the invention. The probability scores for the matches between each polypeptide and its homolog(s) are also shown.  
       [0024] Table 3 shows structural features of polypeptide sequences of the invention, including predicted motifs and domains, along with the methods, algorithms, and searchable databases used for analysis of the polypeptides.  
       [0025] Table 4 lists the cDNA and/or genomic DNA fragments which were used to assemble polynucleotide sequences of the invention, along with selected fragments of the polynucleotide sequences.  
       [0026] Table 5 shows the representative cDNA library for polynucleotides of the invention.  
       [0027] Table 6 provides an appendix which describes the tissues and vectors used for construction of the cDNA libraries shown in Table 5.  
       [0028] Table 7 shows the tools, programs, and algorithms used to analyze the polynucleotides and polypeptides of the invention, along with applicable descriptions, references, and threshold parameters.  
       DESCRIPTION OF THE INVENTION  
       [0029] Before the present proteins, nucleotide sequences, and methods are described, it is understood that this invention is not limited to the particular machines, materials and methods described, as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims.  
       [0030] It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to “a host cell” includes a plurality of such host cells, and a reference to “an antibody” is a reference to one or more antibodies and equivalents thereof known to those skilled in the art, and so forth.  
       [0031] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any machines, materials, and methods similar or equivalent to those described herein can be used to practice or test the present invention, the preferred machines, materials and methods are now described. All publications mentioned herein are cited for the purpose of describing and disclosing the cell lines, protocols, reagents and vectors which are reported in the publications and which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.  
       [0032] Definitions  
       [0033] “MDDT” refers to the amino acid sequences of substantially purified MDDT obtained from any species, particularly a mammalian species, including bovine, ovine, porcine, murine, equine, and human, and from any source, whether natural, synthetic, semi-synthetic, or recombinant.  
       [0034] The term “agonist” refers to a molecule which intensifies or mimics the biological activity of MDDT. Agonists may include proteins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of MDDT either by directly interacting with MDDT or by acting on components of the biological pathway in which MDDT participates.  
       [0035] An “allelic variant” is an alternative form of the gene encoding MDDT. Allelic variants may result from at least one mutation in the nucleic acid sequence and may result in altered mRNAs or in polypeptides whose structure or function may or may not be altered. A gene may have none, one, or many allelic variants of its naturally occurring form. Common mutational changes which give rise to allelic variants are generally ascribed to natural deletions, additions, or substitutions of nucleotides. Each of these types of changes may occur alone, or in combination with the others, one or more times in a given sequence.  
       [0036] “Altered” nucleic acid sequences encoding MDDT include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as MDDT or a polypeptide with at least one functional characteristic of MDDT. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding MDDT, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding MDDT. The encoded protein may also be “altered,” and may contain deletions, insertions, or substitutions of amino acid residues which produce a silent change and result in a functionally equivalent MDDT. Deliberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues, as long as the biological or immunological activity of MDDT is retained. For example, negatively charged amino acids may include aspartic acid and glutamic acid, and positively charged amino acids may include lysine and arginine. Amino acids with uncharged polar side chains having similar hydrophilicity values may include: asparagine and glutamine; and serine and threonine. Amino acids with uncharged side chains having similar hydrophilicity values may include: leucine, isoleucine, and valine; glycine and alanine; and phenylalanine and tyrosine.  
       [0037] The terms “amino acid” and “amino acid sequence” refer to an oligopeptide, peptide, polypeptide, or protein sequence, or a fragment of any of these, and to naturally occurring or synthetic molecules. Where “amino acid sequence” is recited to refer to a sequence of a naturally occurring protein molecule, “amino acid sequence” and like terms are not meant to limit the amino acid sequence to the complete native amino acid sequence associated with the recited protein molecule.  
       [0038] “Amplification” relates to the production of additional copies of a nucleic acid sequence. Amplification is generally carried out using polymerase chain reaction (PCR) technologies well known in the art.  
       [0039] The term “antagonist” refers to a molecule which inhibits or attenuates the biological activity of MDDT. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of MDDT either by directly interacting with MDDT or by acting on components of the biological pathway in which MDDT participates.  
       [0040] The term “antibody” refers to intact immunoglobulin molecules as well as to fragments thereof, such as Fab, F(ab′) 2 , and Fv fragments, which are capable of binding an epitopic determinant. Antibodies that bind MDDT polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or oligopeptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired. Commonly used carriers that are chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet hemocyanin (KLH. The coupled peptide is then used to immunize the animal.  
       [0041] The term “antigenic determinant” refers to that region of a molecule (i.e., an epitope) that makes contact with a particular antibody. When a protein or a fragment of a protein is used to immunize a host animal, numerous regions of the protein may induce the production of antibodies which bind specifically to antigenic determinants (particular regions or three-dimensional structures on the protein). An antigenic determinant may compete with the intact antigen (i.e., the immunogen used to elicit the immune response) for binding to an antibody.  
       [0042] The term “aptamer” refers to a nucleic acid or oligonucleotide molecule that binds to a specific molecular target. Aptamers are derived from an in vitro evolutionary process (e.g., SELEX (Systematic Evolution of Ligands by EXponential Enrichment), described in U.S. Pat. No. 5,270,163), which selects for target-specific aptamer sequences from large combinatorial libraries. Aptamer compositions may be double-stranded or single-stranded, and may include deoxyribonucleotides, ribonucleotides, nucleotide derivatives, or other nucleotide-like molecules. The nucleotide components of an aptamer may have modified sugar groups (e.g., the 2′-OH group of a ribonucleotide may be replaced by 2′-F or 2′-NH 2 ), which may improve a desired property, e.g., resistance to nucleases or longer lifetime in blood. Aptamers may be conjugated to other molecules, e.g., a high molecular weight carrier to slow clearance of the aptamer from the circulatory system. Aptamers may be specifically cross-linked to their cognate ligands, e.g., by photo-activation of a cross-linker. (See, e.g., Brody, E. N. and L. Gold (2000) J. Biotechnol. 74:5-13.)  
       [0043] The term “intramer” refers to an aptamer which is expressed in vivo. For example, a vaccinia virus-based RNA expression system has been used to express specific RNA aptamers at high levels in the cytoplasm of leukocytes (Blind, M. et al. (1999) Proc. Natl Acad. Sci. USA 96:3606-3610).  
       [0044] The term “spiegelmer” refers to an aptamer which includes L-DNA, L-RNA, or other left-handed nucleotide derivatives or nucleotide-like molecules. Aptamers containing left-handed nucleotides are resistant to degradation by naturally occurring enzymes, which normally act on substrates containing right-handed nucleotides.  
       [0045] The term “antisense” refers to any composition capable of base-pairing with the “sense” (coding) strand of a specific nucleic acid sequence. Antisense compositions may include DNA; RNA; peptide nucleic acid (PNA); oligonucleotides having modified backbone linkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides having modified sugar groups such as 2′-methoxyethyl sugars or 2′-methoxyethoxy sugars; or oligonucleotides having modified bases such as 5-methyl cytosine, 2′-deoxyuracil, or 7-deaza-2′-deoxyguanosine. Antisense molecules may be produced by any method including chemical synthesis or transcription. Once introduced into a cell, the complementary antisense molecule base-pairs with a naturally occurring nucleic acid sequence produced by the cell to form duplexes which block either transcription or translation. The designation “negative” or “minus” can refer to the antisense strand, and the designation “positive” or “plus” can refer to the sense strand of a reference DNA molecule.  
       [0046] The term “biologically active” refers to a protein having structural, regulatory, or biochemical functions of a naturally occurring molecule. Likewise, “immunologically active” or “immunogenic” refers to the capability of the natural, recombinant, or synthetic MDDT, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.  
       [0047] “Complementary” describes the relationship between two single-stranded nucleic acid sequences that anneal by base-pairing. For example, 5′-AGT-3′ pairs with its complement, 3′-TCA-5′.  
       [0048] A “composition comprising a given polynucleotide sequence” and a “composition comprising a given amino acid sequence” refer broadly to any composition containing the given polynucleotide or amino acid sequence. The composition may comprise a dry formulation or an aqueous solution. Compositions comprising polynucleotide sequences encoding MDDT or fragments of MDDT may be employed as hybridization probes. The probes may be stored in freeze-dried form and may be associated with a stabilizing agent such as a carbohydrate. In hybridizations, the probe may be deployed in an aqueous solution containing salts (e.g., NaCl), detergents (e.g., sodium dodecyl sulfate; SDS), and other components (e.g., Denhardt&#39;s solution, dry milk, salmon sperm DNA, etc.).  
       [0049] “Consensus sequence” refers to a nucleic acid sequence which has been subjected to repeated DNA sequence analysis to resolve uncalled bases, extended using the XL-PCR kit (Applied Biosystems, Foster City Calif.) in the 5′ and/or the 3′ direction, and resequenced, or which has been assembled from one or more overlapping cDNA, EST, or genomic DNA fragments using a computer program for fragment assembly, such as the GELVIEW fragment assembly system (GCG, Madison Wis.) or Phrap (University of Washington, Seattle Wash.). Some sequences have been both extended and assembled to produce the consensus sequence.  
       [0050] “Conservative amino acid substitutions” are those substitutions that are predicted to least interfere with the properties of the original protein, i.e., the structure and especially the function of the protein is conserved and not significantly changed by such substitutions. The table below shows amino acids which may be substituted for an original amino acid in a protein and which are regarded as conservative amino acid substitutions.  
                                   Original Residue   Conservative Substitution                  Ala   Gly, Ser       Arg   His, Lys       Asn   Asp, Gln, His       Asp   Asn, Glu       Cys   Ala, Ser       Gln   Asn, Glu, His       Glu   Asp, Gln, His       Gly   Ala       His   Asn, Arg, Gln, Glu       Ile   Leu, Val       Leu   Ile, Val       Lys   Arg, Gln, Glu       Met   Leu, Ile       Phe   His, Met, Leu, Trp, Tyr       Ser   Cys, Thr       Thr   Ser, Val       Trp   Phe, Tyr       Tyr   His, Phe, Trp       Val   Ile, Leu, Thr                  
 
       [0051] Conservative amino acid substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical conformation, (b) the charge or hydrophobicity of the molecule at the site of the substitution, and/or (c) the bulk of the side chain.  
       [0052] A “deletion” refers to a change in the amino acid or nucleotide sequence that results in the absence of one or more amino acid residues or nucleotides.  
       [0053] The term “derivative” refers to a chemically modified polynucleotide or polypeptide. Chemical modifications of a polynucleotide can include, for example, replacement of hydrogen by an alkyl, acyl, hydroxyl, or amino group. A derivative polynucleotide encodes a polypeptide which retains at least one biological or immunological function of the natural molecule. A derivative polypeptide is one modified by glycosylation, pegylation, or any similar process that retains at least one biological or immunological function of the polypeptide from which it was derived.  
       [0054] A “detectable label” refers to a reporter molecule or enzyme that is capable of generating a measurable signal and is covalently or noncovalently joined to a polynucleotide or polypeptide.  
       [0055] “Differential expression” refers to increased or upregulated; or decreased, downregulated, or absent gene or protein expression, determined by comparing at least two different samples. Such comparisons may be carried out between, for example, a treated and an untreated sample, or a diseased and a normal sample.  
       [0056] “Exon shuffling” refers to the recombination of different coding regions (exons). Since an exon may represent a structural or functional domain of the encoded protein, new proteins may be assembled through the novel reassortment of stable substructures, thus allowing acceleration of the evolution of new protein functions.  
       [0057] A “fragment” is a unique portion of MDDT or the polynucleotide encoding MDDT which is identical in sequence to but shorter in length than the parent sequence. A fragment may comprise up to the entire length of the defined sequence, minus one nucleotide/amino acid residue. For example, a fragment may comprise from 5 to 1000 contiguous nucleotides or amino acid residues. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, may be at least 5, 10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500 contiguous nucleotides or amino acid residues in length. Fragments may be preferentially selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected from the first 250 or 500 amino acids (or first 25% or 50%) of a polypeptide as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing, tables, and figures, may be encompassed by the present embodiments.  
       [0058] A fragment of SEQ ID NO:13-24 comprises a region of unique polynucleotide sequence that specifically identifies SEQ ID NO:13-24, for example, as distinct from any other sequence in the genome from which the fragment was obtained. A fragment of SEQ ID NO:13-24 is useful, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID NO:13-24 from related polynucleotide sequences. The precise length of a fragment of SEQ ID NO:13-24 and the region of SEQ ID NO:13-24 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0059] A fragment of SEQ ID NO:1-12 is encoded by a fragment of SEQ ID NO:13-24. A fragment of SEQ ID NO:1-12 comprises a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-12. For example, a fragment of SEQ ID NO:1-12 is useful as an immunogenic peptide for the development of antibodies that specifically recognize SEQ ID NO:1-12. The precise length of a fragment of SEQ ID NO:1-12 and the region of SEQ ID NO:1-12 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
       [0060] A “full length” polynucleotide sequence is one containing at least a translation initiation codon (e.g., methionine) followed by an open reading frame and a translation termination codon. A “full length” polynucleotide sequence encodes a “full length” polypeptide sequence.  
       [0061] “Homology” refers to sequence similarity or, interchangeably, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences.  
       [0062] The terms “percent identity” and “% identity,” as applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences.  
       [0063] Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison Wis.). CLUSTAL V is described in Higgins, D. G. and P. M. Sharp (1989) CABIOS 5:151-153 and in Higgins, D. G. et al. (1992) CABIOS 8:189-191. For pairwise alignments of polynucleotide sequences, the default parameters are set as follows: Ktuple=2, gap penalty=5, window=4, and “diagonals saved”=4. The “weighted” residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the “percent similarity” between aligned polynucleotide sequences.  
       [0064] Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment Search Tool (BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, Md., and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis programs including “blastn,” that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases. Also available is a tool called “BLAST 2 Sequences” that is used for direct pairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” can be accessed and used interactively at http://www.ncbi.nlm.nih.gov/gorf/bl2.html. The “BLAST 2 Sequences” tool can be used for both blastn and blastp (discussed below). BLAST programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the “BLAST 2 Sequences” tool Version 2.0.12 (Apr.-21-2000) set at default parameters. Such default parameters may be, for example:  
       [0065] Matrix: BLOSUM62  
       [0066] Reward for match: 1  
       [0067] Penalty for mismatch: −2  
       [0068] Open Gap: 5 and Extension Gap: 2 penalties  
       [0069] Gap×drop-off 50  
       [0070] Expect: 10  
       [0071] Word Size: 11  
       [0072] Filter: on  
       [0073] Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures, or Sequence Listing, may be used to describe a length over which percentage identity may be measured.  
       [0074] Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in a nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that all encode substantially the same protein.  
       [0075] The phrases “percent identity” and “% identity,” as applied to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods take into account conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generally preserve the charge and hydrophobicity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide.  
       [0076] Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3, window=5, and “diagonals saved”=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide alignments, the percent identity is reported by CLUSTAL V as the “percent similarity” between aligned polypeptide sequence pairs.  
       [0077] Alternatively the NCBI BLAST software suite may be used. For example, for a pairwise comparison of two polypeptide sequences, one may use the “BLAST 2 Sequences” tool Version 2.0.12 (Apr.-21-2000) with blastp set at default parameters. Such default parameters may be, for example:  
       [0078] Matrix: BLOSUM62  
       [0079] Open Gap: 11 and Extension Gap: 1 penalties  
       [0080] Gap×drop-off 50  
       [0081] Expect: 10  
       [0082] Word Size: 3  
       [0083] Filter: on  
       [0084] Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured.  
       [0085] “Human artificial chromosomes” (HACs) are linear microchromosomes which may contain DNA sequences of about 6 kb to 10 Mb in size and which contain all of the elements required for chromosome replication, segregation and maintenance.  
       [0086] The term “humanized antibody” refers to an antibody molecule in which the amino acid sequence in the non-antigen binding regions has been altered so that the antibody more closely resembles a human antibody, and still retains its original binding ability.  
       [0087] “Hybridization” refers to the process by which a polynucleotide strand anneals with a complementary strand through base pairing under defined hybridization conditions. Specific hybridization is an indication that two nucleic acid sequences share a high degree of complementarity. Specific hybridization complexes form under permissive annealing conditions and remain hybridized after the “washing” step(s). The washing step(s) is particularly important in determining the stringency of the hybridization process, with more stringent conditions allowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched. Permissive conditions for annealing of nucleic acid sequences are routinely determinable by one of ordinary skill in the art and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency, and therefore hybridization specificity. Permissive annealing conditions occur, for example, at 68° C. in the presence of about 6×SSC, about 1% (w/v) SDS, and about 100 μg/ml sheared, denatured salmon sperm DNA.  
       [0088] Generally, stringency of hybridization is expressed, in part, with reference to the temperature under which the wash step is carried out. Such wash temperatures are typically selected to be about 5° C. to 20° C. lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength and pH. The T m  is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating T m  and conditions for nucleic acid hybridization are well known and can be found in Sambrook, J. et al. (1989)  Molecular Cloning: A Laboratory Manual,  2 nd  ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; specifically see volume 2, chapter 9.  
       [0089] High stringency conditions for hybridization between polynucleotides of the present invention include wash conditions of 68° C. in the presence of about 0.2×SSC and about 0.1% SDS, for 1 hour. Alternatively, temperatures of about 65° C., 60° C., 55° C., or 42° C. may be used. SSC concentration may be varied from about 0.1 to 2×SSC, with SDS being present at about 0.1%. Typically, blocking reagents are used to block non-specific hybridization. Such blocking reagents include, for instance, sheared and denatured salmon sperm DNA at about 100-200 μg/ml. Organic solvent, such as formamide at a concentration of about 35-50% v/v, may also be used under particular circumstances, such as for RNA:DNA hybridizations. Useful variations on these wash conditions will be readily apparent to those of ordinary skill in the art. Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides. Such similarity is strongly indicative of a similar role for the nucleotides and their encoded polypeptides.  
       [0090] The term “hybridization complex” refers to a complex formed between two nucleic acid sequences by virtue of the formation of hydrogen bonds between complementary bases. A hybridization complex may be formed in solution (e.g., C 0 t or R 0 t analysis) or formed between one nucleic acid sequence present in solution and another nucleic acid sequence immobilized on a solid support (e.g., paper, membranes, filters, chips, pins or glass slides, or any other appropriate substrate to which cells or their nucleic acids have been fixed).  
       [0091] The words “insertion” and “addition” refer to changes in an amino acid or nucleotide sequence resulting in the addition of one or more amino acid residues or nucleotides, respectively.  
       [0092] “Immune response” can refer to conditions associated with inflammation, trauma, immune disorders, or infectious or genetic disease, etc. These conditions can be characterized by expression of various factors, e.g., cytokines, chemokines, and other signaling molecules, which may affect cellular and systemic defense systems.  
       [0093] An “immunogenic fragment” is a polypeptide or oligopeptide fragment of MDDT which is capable of eliciting an immune response when introduced into a living organism, for example, a mammal. The term “immunogenic fragment” also includes any polypeptide or oligopeptide fragment of MDDT which is useful in any of the antibody production methods disclosed herein or known in the art.  
       [0094] The term “microarray” refers to an arrangement of a plurality of polynucleotides, polypeptides, or other chemical compounds on a substrate.  
       [0095] The terms “element” and “array element” refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray.  
       [0096] The term “modulate” refers to a change in the activity of MDDT. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of MDDT.  
       [0097] The phrases “nucleic acid” and “nucleic acid sequence” refer to a nucleotide, oligonucleotide, polynucleotide, or any fragment thereof. These phrases also refer to DNA or RNA of genomic or synthetic origin which may be single-stranded or double-stranded and may represent the sense or the antisense strand, to peptide nucleic acid (PNA), or to any DNA-like or RNA-like material.  
       [0098] “Operably linked” refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with a second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Operably linked DNA sequences may be in close proximity or contiguous and, where necessary to join two protein coding regions, in the same reading frame.  
       [0099] “Peptide nucleic acid” (PNA) refers to an antisense molecule or anti-gene agent which comprises an oligonucleotide of at least about 5 nucleotides in length linked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubility to the composition. PNAs preferentially bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their lifespan in the cell.  
       [0100] “Post-translational modification” of an MDDT may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will vary by cell type depending on the enzymatic milieu of MDDT.  
       [0101] “Probe” refers to nucleic acid sequences encoding MDDT, their complements, or fragments thereof, which are used to detect identical, allelic or related nucleic acid sequences. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. “Primers” are short nucleic acids, usually DNA oligonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing. The primer may then be extended along the target DNA strand by a DNA polymerase enzyme. Primer pairs can be used for amplification (and identification) of a nucleic acid sequence, e.g., by the polymerase chain reaction (PCR).  
       [0102] Probes and primers as used in the present invention typically comprise at least 15 contiguous nucleotides of a known sequence. In order to enhance specificity, longer probes and primers may also be employed, such as probes and primers that comprise at least 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides of the disclosed nucleic acid sequences. Probes and primers may be considerably longer than these examples, and it is understood that any length supported by the specification, including the tables, figures, and Sequence Listing, may be used.  
       [0103] Methods for preparing and using probes and primers are described in the references, for example Sambrook, J. et al. (1989)  Molecular Cloning: A Laboratory Manual,  2 nd  ed., vol. 1-3, Cold Spring Harbor Press, Plainview N.Y.; Ausubel, F. M. et al. (1987)  Current Protocols in Molecular Biology , Greene Publ. Assoc. &amp; Wiley-Intersciences, New York N.Y.; Innis, M. et al. (1990)  PCR Protocols, A Guide to Methods and Applications , Academic Press, San Diego Calif.. PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge Mass.).  
       [0104] Oligonucleotides for use as primers are selected using software known in the art for such purpose. For example, OLIGO 4.06 software is useful for the selection of PCR primer pairs of up to 100 nucleotides each, and for the analysis of oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas Tex.) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the public from the Whitehead Institute/MIT Center for Genome Research, Cambridge Mass.) allows the user to input a “mispriming library,” in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user&#39;s specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and conserved oligonucleotides and polynucleotide fragments. The oligonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.  
       [0105] A “recombinant nucleic acid” is a sequence that is not naturally occurring or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence. This artificial combination is often accomplished by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques such as those described in Sambrook, supra. The term recombinant includes nucleic acids that have been altered solely by addition, substitution, or deletion of a portion of the nucleic acid. Frequently, a recombinant nucleic acid may include a nucleic acid sequence operably linked to a promoter sequence. Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a cell.  
       [0106] Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia virus, that could be use to vaccinate a mammal wherein the recombinant nucleic acid is expressed, inducing a protective immunological response in the mammal.  
       [0107] A “regulatory element” refers to a nucleic acid sequence usually derived from untranslated regions of a gene and includes enhancers, promoters, introns, and 5′ and 3′ untranslated regions (UTRs). Regulatory elements interact with host or viral proteins which control transcription, translation, or RNA stability.  
       [0108] “Reporter molecules” are chemical or biochemical moieties used for labeling a nucleic acid, amino acid, or antibody. Reporter molecules include radionuclides; enzymes; fluorescent, chemiluminescent, or chromogenic agents; substrates; cofactors; inhibitors; magnetic particles; and other moieties known in the art.  
       [0109] An “RNA equivalent,” in reference to a DNA sequence, is composed of the same linear sequence of nucleotides as the reference DNA sequence with the exception that all occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0110] The term “sample” is used in its broadest sense. A sample suspected of containing MDDT, nucleic acids encoding MDDT, or fragments thereof may comprise a bodily fluid; an extract from a cell, chromosome, organelle, or membrane isolated from a cell; a cell; genomic DNA, RNA, or cDNA, in solution or bound to a substrate; a tissue; a tissue print; etc.  
       [0111] The terms “specific binding” and “specifically binding” refer to that interaction between a protein or peptide and an agonist, an antibody, an antagonist, a small molecule, or any natural or synthetic binding composition. The interaction is dependent upon the presence of a particular structure of the protein, e.g., the antigenic determinant or epitope, recognized by the binding molecule. For example, if an antibody is specific for epitope “A,” the presence of a polypeptide comprising the epitope A, or the presence of free unlabeled A, in a reaction containing free labeled A and the antibody will reduce the amount of labeled A that binds to the antibody.  
       [0112] The term “substantially purified” refers to nucleic acid or amino acid sequences that are removed from their natural environment and are isolated or separated, and are at least 60% free, preferably at least 75% free, and most preferably at least 90% free from other components with which they are naturally associated.  
       [0113] A “substitution” refers to the replacement of one or more amino acid residues or nucleotides by different amino acid residues or nucleotides, respectively.  
       [0114] “Substrate” refers to any suitable rigid or semi-rigid support including membranes, filters, chips, slides, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles and capillaries. The substrate can have a variety of surface forms, such as wells, trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound.  
       [0115] A “transcript image” or “expression profile” refers to the collective pattern of gene expression by a particular cell type or tissue under given conditions at a given time.  
       [0116] “Transformation” describes a process by which exogenous DNA is introduced into a recipient cell. Transformation may occur under natural or artificial conditions according to various methods well known in the art, and may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. The method for transformation is selected based on the type of host cell being transformed and may include, but is not limited to, bacteriophage or viral infection, electroporation, heat shock, lipofection, and particle bombardment. The term “transformed cells” includes stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well as transiently transformed cells which express the inserted DNA or RNA for limited periods of time.  
       [0117] A “transgenic organism,” as used herein, is any organism, including but not limited to animals and plants, in which one or more of the cells of the organism contains 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. The transgenic organisms contemplated in accordance with the present invention include bacteria, cyanobacteria, fungi, plants and animals. The isolated DNA of the present invention can be introduced into the host by methods known in the art, for example infection, transfection, transformation or transconjugation. Techniques for transferring the DNA of the present invention into such organisms are widely known and provided in references such as Sambrook et al. (1989), supra.  
       [0118] A “variant” of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 40% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the “BLAST 2 Sequences” tool Version 2.0.9 (May 7, 1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length. A variant may be described as, for example, an “allelic” (as defined above), “splice,” “species,” or “polymorphic” variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser number of polynucleotides due to alternate splicing of exons during mRNA processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule. Species variants are polynucleotide sequences that vary from one species to another. The resulting polypeptides will generally have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species. Polymorphic variants also may encompass “single nucleotide polymorphisms” (SNPs) in which the polynucleotide sequence varies by one nucleotide base. The presence of SNPs may be indicative of, for example, a certain population, a disease state, or a propensity for a disease state.  
       [0119] A “variant” of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the “BLAST 2 Sequences” tool Version 2.0.9 (May 7, 1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length of one of the polypeptides.  
       [0120] THE INVENTION  
       [0121] The invention is based on the discovery of new full-length human molecules for disease detection and treatment (MDDT), the polynucleotides encoding MDDT, and the use of these compositions for the diagnosis, treatment, or prevention of developmental, cell proliferative, and immunological disorders.  
       [0122] Table 1 summarizes the nomenclature for the full length polynucleotide and polypeptide sequences of the invention. Each polynucleotide and its corresponding polypeptide are correlated to a single Incyte project identification number (Incyte Project ID). Each polypeptide sequence is denoted by both a polypeptide sequence identification number (Polypeptide SEQ ID NO:) and an Incyte polypeptide sequence number (Incyte Polypeptide ID) as shown. Each polynucleotide sequence is denoted by both a polynucleotide sequence identification number (Polynucleotide SEQ ID NO:) and an Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) as shown.  
       [0123] Table 2 shows sequences with homology to the polypeptides of the invention as identified by BLAST analysis against the GenBank protein (genpept) database. Columns 1 and 2 show the polypeptide sequence identification number (Polypeptide SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ED) for polypeptides of the invention. Column 3 shows the GenBank identification number (GenBank ID NO:) of the nearest GenBank homolog. Column 4 shows the probability scores for the matches between each polypeptide and its homolog(s). Column 5 shows the annotation of the GenBank homolog(s).  
       [0124] Table 3 shows various structural features of the polypeptides of the invention. Columns 1 and 2 show the polypeptide sequence identification number (SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ID) for each polypeptide of the invention. Column 3 shows the number of amino acid residues in each polypeptide. Column 4 shows potential phosphorylation sites, and column 5 shows potential glycosylation sites, as determined by the MOTIFS program of the GCG sequence analysis software package (Genetics Computer Group, Madison Wis.). Column 6 shows amino acid residues comprising signature sequences, domains, and motifs. Column 7 shows analytical methods for protein structure/function analysis and in some cases, searchable databases to which the analytical methods were applied.  
       [0125] Together, Tables 2 and 3 summarize the properties of polypeptides of the invention, and these properties establish that the claimed polypeptides are full-length human molecules for disease detection and treatment. For example, SEQ ID NO:1 is 67% identical to human IFI16b, an interferon-induced myeloid differentiation transcriptional activator (GenBank ID g8176525) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 3.7e-155, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:1 also contains domains found in IFI16b, as determined by comparison to the DOMO and PRODOM databases of protein domains. (See Table 3.) SEQ ID NO:2-12 were analyzed and annotated in a similar manner. The algorithms and parameters for the analysis of SEQ ID NO:1-12 are described in Table 7.  
       [0126] As shown in Table 4, the full length polynucleotide sequences of the present invention were assembled using cDNA sequences or coding (exon) sequences derived from genomic DNA, or any combination of these two types of sequences. Columns 1 and 2 list the polynucleotide sequence identification number (Polynucleotide SEQ ID NO:) and the corresponding Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) for each polynucleotide of the invention. Column 3 shows the length of each polynucleotide sequence in basepairs. Column 4 lists fragments of the polynucleotide sequences which are useful, for example, in hybridization or amplification technologies that identify SEQ ID NO:13-24 or that distinguish between SEQ ID NO:13-24 and related polynucleotide sequences. Column 5 shows identification numbers corresponding to cDNA sequences, coding sequences (exons) predicted from genomic DNA, and/or sequence assemblages comprised of both cDNA and genomic DNA. These sequences were used to assemble the full length polynucleotide sequences of the invention. Columns 6 and 7 of Table 4 show the nucleotide start (5′) and stop (3′) positions of the cDNA and/or genomic sequences in column 5 relative to their respective full length sequences.  
       [0127] The identification numbers in Column 5 of Table 4 may refer specifically, for example, to Incyte cDNAs along with their corresponding cDNA libraries. For example, 146222R6 is the identification number of an Incyte cDNA sequence, and TLYMNOR01 is the cDNA library from which it is derived. Incyte cDNAs for which cDNA libraries are not indicated were derived from pooled cDNA libraries (e.g., 70788230V1). Alternatively, the identification numbers in column 5 may refer to GenBank cDNAs or ESTs (e.g., g3934182) which contributed to the assembly of the full length polynucleotide sequences. In addition, the identification numbers in column 5 may identify sequences derived from the ENSEMBL (The Sanger Centre, Cambridge, UK) database (i.e., those sequences including the designation “ENST”). Alternatively, the identification numbers in column 5 may be derived from the NCBI RefSeq Nucleotide Sequence Records Database (i.e., those sequences including the designation “NM” or “NT”) or the NCBI RefSeq Protein Sequence Records (i.e., those sequences including the designation “NP”). Alternatively, the identification numbers in column 5 may refer to assemblages of both cDNA and Genscan-predicted exons brought together by an “exon stitching” algorithm. For example, FL_XXXXXX_N 1— N 2— YYYYY_N 3— N 4  represents a “stitched” sequence in which XXXXXX is the identification number of the cluster of sequences to which the algorithm was applied, and YYYYY is the number of the prediction generated by the algorithm, and N 1,2,3 . . .  , if present, represent specific exons that may have been manually edited during analysis (See Example V). Alternatively, the identification numbers in column 5 may refer to assemblages of exons brought together by an “exon-stretching” algorithm, For example, FLXXXXXX_gAAAAA_gBBBBB — 1_N is the identification number of a “stretched” sequence, with XXXXXX being the Incyte project identification number, gAAAAA being the GenBank identification number of the human genomic sequence to which the “exon-stretching” algorithm was applied, gBBBBB being the GenBank identification number or NCBI RefSeq identification number of the nearest GenBank protein homolog, and N referring to specific exons (See Example V). In instances where a RefSeq sequence was used as a protein homolog for the “exon-stretching” algorithm, a RefSeq identifier (denoted by “NM,” “NP,” or “NT”) may be used in place of the GenBank identifier (i.e., gBBBBB).  
       [0128] Alternatively, a prefix identifies component sequences that were hand-edited, predicted from genomic DNA sequences, or derived from a combination of sequence analysis methods. The following Table lists examples of component sequence prefixes and corresponding sequence analysis methods associated with the prefixes (see Example IV and Example V).  
                                   Prefix   Type of analysis and/or examples of programs                  GNN, GFG,   Exon prediction from genomic sequences using, for       ENST   example, GENSCAN (Stanford University, CA, USA) or           FGENES (Computer Genomics Group,           The Sanger Centre, Cambridge, UK).       GBI   Hand-edited analysis of genomic sequences.       FL   Stitched or stretched genomic sequences (see Example V).       INCY   Full length transcript and exon prediction from mapping           of EST sequences to the genome. Genomic location           and EST composition data are combined to           predict the exons and resulting transcript.                  
 
       [0129] In some cases, Incyte cDNA coverage redundant with the sequence coverage shown in column 5 was obtained to confirm the final consensus polynucleotide sequence, but the relevant Incyte cDNA identification numbers are not shown.  
       [0130] Table 5 shows the representative cDNA libraries for those full length polynucleotide sequences which were assembled using Incyte cDNA sequences. The representative cDNA library is the Incyte cDNA library which is most frequently represented by the Incyte cDNA sequences which were used to assemble and confirm the above polynucleotide sequences. The tissues and vectors which were used to construct the cDNA libraries shown in Table 5 are described in Table 6.  
       [0131] The invention also encompasses MDDT variants. A preferred MDDT variant is one which has at least about 80%, or alternatively at least about 90%, or even at least about 95% amino acid sequence identity to the MDDT amino acid sequence, and which contains at least one functional or structural characteristic of MDDT.  
       [0132] The invention also encompasses polynucleotides which encode MDDT. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:13-24, which encodes MDDT. The polynucleotide sequences of SEQ ID NO:13-24, as presented in the Sequence Listing, embrace the equivalent RNA sequences, wherein occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose.  
       [0133] The invention also encompasses a variant of a polynucleotide sequence encoding MDDT. In particular, such a variant polynucleotide sequence will have at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to the polynucleotide sequence encoding MDDT. A particular aspect of the invention encompasses a variant of a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:13-24 which has at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NO:13-24. Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of MDDT.  
       [0134] In addition, or in the alternative, a polynucleotide variant of the invention is a splice variant of a polynucleotide sequence encoding MDDT. A splice variant may have portions which have significant sequence identity to the polynucleotide sequence encoding MDDT, but will generally have a greater or lesser number of polynucleotides due to additions or deletions of blocks of sequence arising from alternate splicing of exons during mRNA processing. A splice variant may have less than about 70%, or alternatively less than about 60%, or alternatively less than about 50% polynucleotide sequence identity to the polynucleotide sequence encoding MDDT over its entire length; however, portions of the splice variant will have at least about 70%, or alternatively at least about 85%, or alternatively at least about 95%, or alternatively 100% polynucleotide sequence identity to portions of the polynucleotide sequence encoding MDDT. Any one of the splice variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of MDDT.  
       [0135] It will be appreciated by those skilled in the art that as a result of the degeneracy of the genetic code, a multitude of polynucleotide sequences encoding MDDT, some bearing minimal similarity to the polynucleotide sequences of any known and naturally occurring gene, may be produced. Thus, the invention contemplates each and every possible variation of polynucleotide sequence that could be made by selecting combinations based on possible codon choices. These combinations are made in accordance with the standard triplet genetic code as applied to the polynucleotide sequence of naturally occurring MDDT, and all such variations are to be considered as being specifically disclosed.  
       [0136] Although nucleotide sequences which encode MDDT and its variants are generally capable of hybridizing to the nucleotide sequence of the naturally occurring MDDT under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding MDDT or its derivatives possessing a substantially different codon usage, e.g., inclusion of non-naturally occurring codons. Codons may be selected to increase the rate at which expression of the peptide occurs in a particular prokaryotic or eukaryotic host in accordance with the frequency with which particular codons are utilized by the host. Other reasons for substantially altering the nucleotide sequence encoding MDDT and its derivatives without altering the encoded amino acid sequences include the production of RNA transcripts having more desirable properties, such as a greater half-life, than transcripts produced from the naturally occurring sequence.  
       [0137] The invention also encompasses production of DNA sequences which encode MDDT and MDDT derivatives, or fragments thereof, entirely by synthetic chemistry. After production, the synthetic sequence may be inserted into any of the many available expression vectors and cell systems using reagents well known in the art. Moreover, synthetic chemistry may be used to introduce mutations into a sequence encoding MDDT or any fragment thereof.  
       [0138] Also encompassed by the invention are polynucleotide sequences that are capable of hybridizing to the claimed polynucleotide sequences, and, in particular, to those shown in SEQ ID NO:13-24 and fragments thereof under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A. R. (1987) Methods Enzymol. 152:507-511.) Hybridization conditions, including annealing and wash conditions, are described in “Definitions.” 
       [0139] Methods for DNA sequencing are well known in the art and may be used to practice any of the embodiments of the invention. The methods may employ such enzymes as the Klenow fragment of DNA polymerase I, SEQUENASE (US Biochemical, Cleveland Ohio), Taq polymerase (Applied Biosystems), thermostable T7 polymerase (Amersham Pharmacia Biotech, Piscataway N.J.), or combinations of polymerases and proofreading exonucleases such as those found in the ELONGASE amplification system (Life Technologies, Gaithersburg Md.). Preferably, sequence preparation is automated with machines such as the MICROLAB 2200 liquid transfer system (Hamilton, Reno Nev.), PTC200 thermal cycler (MJ Research, Watertown Mass.) and ABI CATALYST 800 thermal cycler (Applied Biosystems). Sequencing is then carried out using either the ABI 373 or 377 DNA sequencing system (Applied Biosystems), the MEGABACE 1000 DNA sequencing system (Molecular Dynamics, Sunnyvale Calif.), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are well known in the art. (See, e.g., Ausubel, F. M. (1997)  Short Protocols in Molecular Biology , John Wiley &amp; Sons, New York N.Y., unit 7.7; Meyers, R. A. (1995)  Molecular Biology and Biotechnology , Wiley VCH, New York N.Y., pp. 856-853.)  
       [0140] The nucleic acid sequences encoding MDDT may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences, such as promoters and regulatory elements. For example, one method which may be employed, restriction-site PCR, uses universal and nested primers to amplify unknown sequence from genomic DNA within a cloning vector. (See, e.g., Sarkar, G. (1993) PCR Methods Applic. 2:318-322.) Another method, inverse PCR, uses primers that extend in divergent directions to amplify unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences. (See, e.g., Triglia, T. et al. (1988) Nucleic Acids Res. 16:8186.) A third method, capture PCR, involves PCR amplification of DNA fragments adjacent to known sequences in human and yeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al. (1991) PCR Methods Applic. 1:111-119.) In this method, multiple restriction enzyme digestions and ligations may be used to insert an engineered double-stranded sequence into a region of unknown sequence before performing PCR. Other methods which may be used to retrieve unknown sequences are known in the art. (See, e.g., Parker, J. D. et al. (1991) Nucleic Acids Res. 19:3055-3060). Additionally, one may use PCR, nested primers, and PROMOTERFINDER libraries (Clontech, Palo Alto Calif.) to walk genomic DNA. This procedure avoids the need to screen libraries and is useful in finding intron/exon junctions. For all PCR-based methods, primers may be designed using commercially available software, such as OLIGO 4.06 primer analysis software (National Biosciences, Plymouth Minn.) or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the template at temperatures of about 68° C. to 72° C.  
       [0141] When screening for full length cDNAs, it is preferable to use libraries that have been size-selected to include larger cDNAs. In addition, random-primed libraries, which often include sequences containing the 5′ regions of genes, are preferable for situations in which an oligo d(T) library does not yield a full-length cDNA. Genomic libraries may be useful for extension of sequence into 5′ non-transcribed regulatory regions.  
       [0142] Capillary electrophoresis systems which are commercially available may be used to analyze the size or confirm the nucleotide sequence of sequencing or PCR products. In particular, capillary sequencing may employ flowable polymers for electrophoretic separation, four different nucleotide-specific, laser-stimulated fluorescent dyes, and a charge coupled device camera for detection of the emitted wavelengths. Output/light intensity may be converted to electrical signal using appropriate software (e.g., GENOTYPER and SEQUENCE NAVIGATOR, Applied Biosystems), and the entire process from loading of samples to computer analysis and electronic data display may be computer controlled. Capillary electrophoresis is especially preferable for sequencing small DNA fragments which may be present in limited amounts in a particular sample.  
       [0143] In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode MDDT may be cloned in recombinant DNA molecules that direct expression of MDDT, or fragments or functional equivalents thereof, in appropriate host cells. Due to the inherent degeneracy of the genetic code, other DNA sequences which encode substantially the same or a functionally equivalent amino acid sequence may be produced and used to express MDDT.  
       [0144] The nucleotide sequences of the present invention can be engineered using methods generally known in the art in order to alter MDDT-encoding sequences for a variety of purposes including, but not limited to, modification of the cloning, processing, and/or expression of the gene product. DNA shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oligonucleotides may be used to engineer the nucleotide sequences. For example, oligonucleotide-mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, produce splice variants, and so forth.  
       [0145] The nucleotides of the present invention may be subjected to DNA shuffling techniques such as MOLECULARBREEDING (Maxygen Inc., Santa Clara Calif.; described in U.S. Pat. No. 5,837,458; Chang, C. -C. et al. (1999) Nat. Biotechnol. 17:793-797; Christians, F. C. et al. (1999) Nat. Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol. 14:315-319) to alter or improve the biological properties of MDDT, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library is then subjected to selection or screening procedures that identify those gene variants with the desired properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selection/screening. Thus, genetic diversity is created through “artificial” breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of homologous genes in the same gene family, either from the same or different species, thereby maximizing the genetic diversity of multiple naturally occurring genes in a directed and controllable manner.  
       [0146] In another embodiment, sequences encoding MDDT may be synthesized, in whole or in part, using chemical methods well known in the art. (See, e.g., Caruthers, M. H. et al. (1980) Nucleic Acids Symp. Ser. 7:215-223; and Horn, T. et al. (1980) Nucleic Acids Symp. Ser. 7:225-232.) Alternatively, MDDT itself or a fragment thereof may be synthesized using chemical methods. For example, peptide synthesis can be performed using various solution-phase or solid-phase techniques. (See, e.g., Creighton, T. (1984)  Proteins. Structures and Molecular Properties , W H Freeman, New York N.Y., pp. 55-60; and Roberge, J. Y. et al. (1995) Science 269:202-204.) Automated synthesis may be achieved using the ABI 431A peptide synthesizer (Applied Biosystems). Additionally, the amino acid sequence of MDDT, or any part thereof, may be altered during direct synthesis and/or combined with sequences from other proteins, or any part thereof, to produce a variant polypeptide or a polypeptide having a sequence of a naturally occurring polypeptide.  
       [0147] The peptide may be substantially purified by preparative high performance liquid chromatography. (See, e.g., Chiez, R. M. and F. Z. Regnier (1990) Methods Enzymol. 182:392-421.) The composition of the synthetic peptides may be confirmed by amino acid analysis or by sequencing. (See, e.g., Creighton, supra, pp. 28-53.)  
       [0148] In order to express a biologically active MDDT, the nucleotide sequences encoding MDDT or derivatives thereof may be inserted into an appropriate expression vector, i.e., a vector which contains the necessary elements for transcriptional and translational control of the inserted coding sequence in a suitable host. These elements include regulatory sequences, such as enhancers, constitutive and inducible promoters, and 5′ and 3′ untranslated regions in the vector and in polynucleotide sequences encoding MDDT. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of sequences encoding MDDT. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding MDDT and its initiation codon and upstream regulatory sequences are inserted into the appropriate expression vector, no additional transcriptional or translational control signals may be needed. However, in cases where only coding sequence, or a fragment thereof, is inserted, exogenous translational control signals including an in-frame ATG initiation codon should be provided by the vector. Exogenous translational elements and initiation codons may be of various origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of enhancers appropriate for the particular host cell system used. (See, e.g., Scharf, D. et al. (1994) Results Probl. Cell Differ. 20:125-162.)  
       [0149] Methods which are well known to those skilled in the art may be used to construct expression vectors containing sequences encoding MDDT and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, J. et al. (1989)  Molecular Cloning, A Laboratory Manual , Cold Spring Harbor Press, Plainview N.Y., ch. 4, 8, and 16-17; Ausubel, F. M. et al. (1995)  Current Protocols in Molecular Biology , John Wiley &amp; Sons, New York N.Y., ch. 9, 13, and 16.)  
       [0150] A variety of expression vector/host systems may be utilized to contain and express sequences encoding MDDT. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect cell systems infected with viral expression vectors (e.g., baculovirus); plant cell systems transformed with viral expression vectors (e.g., cauliflower mosaic virus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal cell systems. (See, e.g., Sambrook, supra; Ausubel, supra; Van Heeke, G. and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Engelhard, E. K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO J. 6:307-311 ; The McGraw Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659; and  
       [0151] Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355.) Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids, may be used for delivery of nucleotide sequences to the targeted organ, tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Proc. Natl. Acad. Sci. USA 90(13):6340-6344; Buller, R. M. et al. (1985) Nature 317(6040):813-815; McGregor, D. P. et al. (1994) Mol. Immunol. 31(3):219-226; and Verma, I. M. and N. Somia (1997) Nature 389:239-242.) The invention is not limited by the host cell employed.  
       [0152] In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding MDDT. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding MDDT can be achieved using a multifunctional  E. coli  vector such as PBLUESCRIPT (Stratagene, La Jolla Calif.) or PSPORT1 plasmid (Life Technologies). Ligation of sequences encoding MDDT into the vector&#39;s multiple cloning site disrupts the lacZ gene, allowing a calorimetric screening procedure for identification of transformed bacteria containing recombinant molecules. In addition, these vectors may be useful for in vitro transcription, dideoxy sequencing, single strand rescue with helper phage, and creation of nested deletions in the cloned sequence. (See, e.g., Van Heeke, G. and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509.) When large quantities of MDDT are needed, e.g. for the production of antibodies, vectors which direct high level expression of MDDT may be used. For example, vectors containing the strong, inducible SP6 or T7 bacteriophage promoter may be used.  
       [0153] Yeast expression systems may be used for production of MDDT. A number of vectors containing constitutive or inducible promoters, such as alpha factor, alcohol oxidase, and PGH promoters, may be used in the yeast  Saccharomyces cerevisiae  or  Pichia pastoris . In addition, such vectors direct either the secretion or intracellular retention of expressed proteins and enable integration of foreign sequences into the host genome for stable propagation. (See, e.g., Ausubel, 1995, supra; Bitter, G. A. et al. (1987) Methods Enzymol. 153:516-544; and Scorer, C. A. et al. (1994) Bio/Technology 12:181-184.)  
       [0154] Plant systems may also be used for expression of MDDT. Transcription of sequences encoding MDDT may be driven by viral promoters, e.g., the 35S and 19S promoters of CaMV used alone or in combination with the omega leader sequence from TMV (Takamatsu, N. (1987) EMBO J. 6:307-311). Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters may be used. (See, e.g., Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al. (1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105.) These constructs can be introduced into plant cells by direct DNA transformation or pathogen-mediated transfection. (See, e.g.,  The McGraw Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196.)  
       [0155] In mammalian cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, sequences encoding MDDT may be ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a nonessential E1 or E3 region of the viral genome may be used to obtain infective virus which expresses MDDT in host cells. (See, e.g., Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcription enhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used to increase expression in mammalian host cells. SV40 or EBV-based vectors may also be used for high-level protein expression.  
       [0156] Human artificial chromosomes (HACs) may also be employed to deliver larger fragments of DNA than can be contained in and expressed from a plasmid. HACs of about 6 kb to 10 Mb are constructed and delivered via conventional delivery methods (liposomes, polycationic amino polymers, or vesicles) for therapeutic purposes. (See, e.g., Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355.)  
       [0157] For long term production of recombinant proteins in mammalian systems, stable expression of MDDT in cell lines is preferred. For example, sequences encoding MDDT can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. Following the introduction of the vector, cells may be allowed to grow for about 1 to 2 days in enriched media before being switched to selective media. The purpose of the selectable marker is to confer resistance to a selective agent, and its presence allows growth and recovery of cells which successfully express the introduced sequences. Resistant clones of stably transformed cells may be propagated using tissue culture techniques appropriate to the cell type.  
       [0158] Any number of selection systems may be used to recover transformed cell lines. These include, but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk −  and apr −  cells, respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G-418; and als and pat confer resistance to chlorsulfuron and phosphinotricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., trpB and hisD, which alter cellular requirements for metabolites. (See, e.g., Hartman, S. C. and R. C. Mulligan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), β glucuronidase and its substrate β-glucuronide, or luciferase and its substrate luciferin may be used. These markers can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system. (See, e.g., Rhodes, C. A. (1995) Methods Mol. Biol. 55:121-131.)  
       [0159] Although the presence/absence of marker gene expression suggests that the gene of interest is also present, the presence and expression of the gene may need to be confirmed. For example, if the sequence encoding MDDT is inserted within a marker gene sequence, transformed cells containing sequences encoding MDDT can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding MDDT under the control of a single promoter. Expression of the marker gene in response to induction or selection usually indicates expression of the tandem gene as well.  
       [0160] In general, host cells that contain the nucleic acid sequence encoding MDDT and that express MDDT may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA-DNA or DNA-RNA hybridizations, PCR amplification, and protein bioassay or immunoassay techniques which include membrane, solution, or chip based technologies for the detection and/or quantification of nucleic acid or protein sequences.  
       [0161] Immunological methods for detecting and measuring the expression of MDDT using either specific polyclonal or monoclonal antibodies are known in the art. Examples of such techniques include enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), and fluorescence activated cell sorting (FACS). A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering epitopes on MDDT is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art. (See, e.g., Hampton, R. et al. (1990)  Serological Methods. a Laboratory Manual , APS Press, St. Paul Minn., Sect. IV; Coligan, J. E. et al. (1997)  Current Protocols in Immunology , Greene Pub. Associates and Wiley-Interscience, New York N.Y.; and Pound, J. D. (1998)  Immunochemical Protocols , Humana Press, Totowa N.J.)  
       [0162] A wide variety of labels and conjugation techniques are known by those skilled in the art and may be used in various nucleic acid and amino acid assays. Means for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides encoding MDDT include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide. Alternatively, the sequences encoding MDDT, or any fragments thereof, may be cloned into a vector for the production of an mRNA probe. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7, T3, or SP6 and labeled nucleotides. These procedures may be conducted using a variety of commercially available kits, such as those provided by Amersham Pharmacia Biotech, Promega (Madison Wis.), and US Biochemical. Suitable reporter molecules or labels which may be used for ease of detection include radionuclides, enzymes, fluorescent, chemiluminescent, or chromogenic agents, as well as substrates, cofactors, inhibitors, magnetic particles, and the like.  
       [0163] Host cells transformed with nucleotide sequences encoding MDDT may be cultured under conditions suitable for the expression and recovery of the protein from cell culture. The protein produced by a transformed cell may be secreted or retained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing polynucleotides which encode MDDT may be designed to contain signal sequences which direct secretion of MDDT through a prokaryotic or eukaryotic cell membrane.  
       [0164] In addition, a host cell strain may be chosen for its ability to modulate expression of the inserted sequences or to process the expressed protein in the desired fashion. Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing which cleaves a “prepro” or “pro” form of the protein may also be used to specify protein targeting, folding, and/or activity. Different host cells which have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available from the American Type Culture Collection (ATCC, Manassas Va.) and may be chosen to ensure the correct modification and processing of the foreign protein.  
       [0165] In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding MDDT may be ligated to a heterologous sequence resulting in translation of a fusion protein in any of the aforementioned host systems. For example, a chimeric MDDT protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of MDDT activity. Heterologous protein and peptide moieties may also facilitate purification of fusion proteins using commercially available affinity matrices. Such moieties include, but are not limited to, glutathione S-transferase (GST), maltose binding protein (MBP), thioredoxin (Trx), calmodulin binding peptide (CBP), 6-His, FLAG, c-myc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and 6-His enable purification of their cognate fusion proteins on immobilized glutathione, maltose, phenylarsine oxide, calmodulin, and metal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin (HA) enable immunoaffinity purification of fusion proteins using commercially available monoclonal and polyclonal antibodies that specifically recognize these epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the MDDT encoding sequence and the heterologous protein sequence, so that MDDT may be cleaved away from the heterologous moiety following purification. Methods for fusion protein expression and purification are discussed in Ausubel (1995, supra, ch. 10). A variety of commercially available kits may also be used to facilitate expression and purification of fusion proteins.  
       [0166] In a further embodiment of the invention, synthesis of radiolabeled MDDT may be achieved in vitro using the TNT rabbit reticulocyte lysate or wheat germ extract system (Promega). These systems couple transcription and translation of protein-coding sequences operably associated with the T7, T3, or SP6 promoters. Translation takes place in the presence of a radiolabeled amino acid precursor, for example,  35 S-methionine.  
       [0167] MDDT of the present invention or fragments thereof may be used to screen for compounds that specifically bind to MDDT. At least one and up to a plurality of test compounds may be screened for specific binding to MDDT. Examples of test compounds include antibodies, oligonucleotides, proteins (e.g., receptors), or small molecules.  
       [0168] In one embodiment, the compound thus identified is closely related to the natural ligand of MDDT, e.g., a ligand or fragment thereof, a natural substrate, a structural or functional mimetic, or a natural binding partner. (See, e.g., Coligan, J. E. et al. (1991)  Current Protocols in Immunology  1(2): Chapter 5.) Similarly, the compound can be closely related to the natural receptor to which MDDT binds, or to at least a fragment of the receptor, e.g., the ligand binding site. In either case, the compound can be rationally designed using known techniques. In one embodiment, screening for these compounds involves producing appropriate cells which express MDDT, either as a secreted protein or on the cell membrane. Preferred cells include cells from mammals, yeast, Drosophila, or  E. coli . Cells expressing MDDT or cell membrane fractions which contain MDDT are then contacted with a test compound and binding, stimulation, or inhibition of activity of either MDDT or the compound is analyzed.  
       [0169] An assay may simply test binding of a test compound to the polypeptide, wherein binding is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label. For example, the assay may comprise the steps of combining at least one test compound with MDDT, either in solution or affixed to a solid support, and detecting the binding of MDDT to the compound. Alternatively, the assay may detect or measure binding of a test compound in the presence of a labeled competitor. Additionally, the assay may be carried out using cell-free preparations, chemical libraries, or natural product mixtures, and the test compound(s) may be free in solution or affixed to a solid support.  
       [0170] MDDT of the present invention or fragments thereof may be used to screen for compounds that modulate the activity of MDDT. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodiment, an assay is performed under conditions permissive for MDDT activity, wherein MDDT is combined with at least one test compound, and the activity of MDDT in the presence of a test compound is compared with the activity of MDDT in the absence of the test compound. A change in the activity of MDDT in the presence of the test compound is indicative of a compound that modulates the activity of MDDT. Alternatively, a test compound is combined with an in vitro or cell-free system comprising MDDT under conditions suitable for MDDT activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of MDDT may do so indirectly and need not come in direct contact with the test compound. At least one and up to a plurality of test compounds may be screened.  
       [0171] In another embodiment, polynucleotides encoding MDDT or their mammalian homologs may be “knocked out” in an animal model system using homologous recombination in embryonic stem (ES) cells. Such techniques are well known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Pat. No. 5,175,383 and U.S. Pat. No. 5,767,337.) For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture. The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphotransferase gene (neo; Capecchi, M. R. (1989) Science 244:1288-1292). The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-loxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (Marth, J. D. (1996) Clin. Invest. 97:1999-2002; Wagner, K. U. et al. (1997) Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identified and microinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgically transferred to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents.  
       [0172] Polynucleotides encoding MDDT may also be manipulated in vitro in ES cells derived from human blastocysts. Human ES cells have the potential to differentiate into at least eight separate cell lineages including endoderm, mesoderm, and ectodermal cell types. These cell lineages differentiate into, for example, neural cells, hematopoietic lineages, and cardiomyocytes (Thomson, J. A. et al. (1998) Science 282:1145-1147).  
       [0173] Polynucleotides encoding MDDT can also be used to create “knockin” humanized animals (pigs) or transgenic animals (mice or rats) to model human disease. With knockin technology, a region of a polynucleotide encoding MDDT is injected into animal ES cells, and the injected sequence integrates into the animal cell genome. Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal inbred to overexpress MDDT, e.g., by secreting MDDT in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74).  
       [0174] Therapeutics  
       [0175] Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of MDDT and full-length human molecules for disease detection and treatment. In addition, the expression of MDDT is closely associated with brain, reproductive, hemic, lung, pancreatic, nasal, and tumorous tissues. Therefore, MDDT appears to play a role in developmental, cell proliferative, and immunological disorders. In the treatment of disorders associated with increased MDDT expression or activity, it is desirable to decrease the expression or activity of MDDT. In the treatment of disorders associated with decreased MDDT expression or activity, it is desirable to increase the expression or activity of MDDT.  
       [0176] Therefore, in one embodiment, MDDT or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of MDDT. Examples of such disorders include, but are not limited to, a developmental disorder such as renal tubular acidosis, anemia, Cushing&#39;s syndrome, achondroplastic dwarfism, Duchenne and Becker muscular dystrophy, epilepsy, gonadal dysgenesis, WAGR syndrome (Wilms&#39; tumor, aniridia, genitourinary abnormalities, and mental retardation), Smith-Magenis syndrome, myelodysplastic syndrome, hereditary mucoepithelial dysplasia, hereditary keratodermas, hereditary neuropathies such as Charcot-Marie-Tooth disease and neurofibromatosis, hypothyroidism, hydrocephalus, a seizure disorder such as Syndenham&#39;s chorea and cerebral palsy, spina bifida, anencephaly, craniorachischisis, congenital glaucoma, cataract, and sensorineural hearing loss; a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, a cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; and an immunological disorder such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison&#39;s disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture&#39;s syndrome, gout, Graves&#39; disease, Hashimoto&#39;s thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter&#39;s syndrome, rheumatoid arthritis, scleroderma, Sjögren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma.  
       [0177] In another embodiment, a vector capable of expressing MDDT or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of MDDT including, but not limited to, those described above.  
       [0178] In a further embodiment, a composition comprising a substantially purified MDDT in conjunction with a suitable pharmaceutical carrier may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of MDDT including, but not limited to, those provided above.  
       [0179] In still another embodiment, an agonist which modulates the activity of MDDT may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of MDDT including, but not limited to, those listed above.  
       [0180] In a further embodiment, an antagonist of MDDT may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of MDDT. Examples of such disorders include, but are not limited to, those developmental, cell proliferative, and immunological disorders described above. In one aspect, an antibody which specifically binds MDDT may be used directly as an antagonist or indirectly as a targeting or delivery mechanism for bringing a pharmaceutical agent to cells or tissues which express MDDT.  
       [0181] In an additional embodiment, a vector expressing the complement of the polynucleotide encoding MDDT may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of MDDT including, but not limited to, those described above.  
       [0182] In other embodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects.  
       [0183] An antagonist of MDDT may be produced using methods which are generally known in the art. In particular, purified MDDT may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind MDDT. Antibodies to MDDT may also be generated using methods that are well known in the art. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression library. Neutralizing antibodies (i.e., those which inhibit dimer formation) are generally preferred for therapeutic use.  
       [0184] For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with MDDT or with any fragment or oligopeptide thereof which has immunogenic properties. Depending on the host species, various adjuvants may be used to increase immunological response. Such adjuvants include, but are not limited to, Freund&#39;s, mineral gels such as aluminum hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, KLH, and dinitrophenol. Among adjuvants used in humans, BCG (bacilli Calmette-Guerin) and  Corynebacterium parvum  are especially preferable.  
       [0185] It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to MDDT have an amino acid sequence consisting of at least about 5 amino acids, and generally will consist of at least about 10 amino acids. It is also preferable that these oligopeptides, peptides, or fragments are identical to a portion of the amino acid sequence of the natural protein. Short stretches of MDDT amino acids may be fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced.  
       [0186] Monoclonal antibodies to MDDT may be prepared using any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique, the human B-cell hybridoma technique, and the EBV-hybridoma technique. (See, e.g., Kohler, G. et al. (1975) Nature 256:495497; Kozbor, D. et al. (1985) J. Immunol. Methods 81:31-42; Cote, R. J. et al. (1983) Proc. Natl. Acad. Sci. USA 80:2026-2030; and Cole, S. P. et al. (1984) Mol. Cell Biol. 62:109-120.)  
       [0187] In addition, techniques developed for the production of “chimeric antibodies,” such as the splicing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity, can be used. (See, e.g., Morrison, S. L. et al. (1984) Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M. S. et al. (1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature 314:452-454.) Alternatively, techniques described for the production of single chain antibodies may be adapted, using methods known in the art, to produce MDDT-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, may be generated by chain shuffling from random combinatorial immunoglobulin libraries. (See, e.g., Burton, D. R. (1991) Proc. Natl. Acad. Sci. USA 88:10134-10137.)  
       [0188] Antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening immunoglobulin libraries or panels of highly specific binding reagents as disclosed in the literature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci. USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.)  
       [0189] Antibody fragments which contain specific binding sites for MDDT may also be generated. For example, such fragments include, but are not limited to, F(ab′) 2  fragments produced by pepsin digestion of the antibody molecule and Fab fragments generated by reducing the disulfide bridges of the F(ab′)2 fragments. Alternatively, Fab expression libraries may be constructed to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity. (See, e.g., Huse, W. D. et al. (1989) Science 246:1275-1281.)  
       [0190] Various immunoassays may be used for screening to identify antibodies having the desired specificity. Numerous protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with established specificities are well known in the art. Such immunoassays typically involve the measurement of complex formation between MDDT and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering MDDT epitopes is generally used, but a competitive binding assay may also be employed (Pound, supra).  
       [0191] Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques may be used to assess the affinity of antibodies for MDDT. Affinity is expressed as an association constant, K a , which is defined as the molar concentration of MDDT-antibody complex divided by the molar concentrations of free antigen and free antibody under equilibrium conditions. The K a  determined for a preparation of polyclonal antibodies, which are heterogeneous in their affinities for multiple MDDT epitopes, represents the average affinity, or avidity, of the antibodies for MDDT. The K a  determined for a preparation of monoclonal antibodies, which are monospecific for a particular MDDT epitope, represents a true measure of affinity. High-affinity antibody preparations with K a  ranging from about 10 9  to 10 12  L/mole are preferred for use in immunoassays in which the MDDT-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with K a  ranging from about 10 6  to 10 7  L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of MDDT, preferably in active form, from the antibody (Catty, D. (1988)  Antibodies, Volume I: A Practical Approach , IRL Press, Washington D.C.; Liddell, J. E. and A. Cryer (1991)  A Practical Guide to Monoclonal Antibodies , John Wiley &amp; Sons, New York N.Y.).  
       [0192] The titer and avidity of polyclonal antibody preparations may be further evaluated to determine the quality and suitability of such preparations for certain downstream applications. For example, a polyclonal antibody preparation containing at least 1-2 mg specific antibody/ml, preferably 5-10 mg specific antibody/ml, is generally employed in procedures requiring precipitation of MDDT-antibody complexes. Procedures for evaluating antibody specificity, titer, and avidity, and guidelines for antibody quality and usage in various applications, are generally available. (See, e.g., Catty, supra, and Coligan et al. supra.)  
       [0193] In another embodiment of the invention, the polynucleotides encoding MDDT, or any fragment or complement thereof, may be used for therapeutic purposes. In one aspect, modifications of gene expression can be achieved by designing complementary sequences or antisense molecules (DNA, RNA, PNA, or modified oligonucleotides) to the coding or regulatory regions of the gene encoding MDDT. Such technology is well known in the art, and antisense oligonucleotides or larger fragments can be designed from various locations along the coding or control regions of sequences encoding MDDT. (See, e.g., Agrawal, S., ed. (1996)  Antisense Therapeutics , Humana Press Inc., Totawa N.J.)  
       [0194] In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein. (See, e.g., Slater, J. E. et al. (1998) J. Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K. J. et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as retrovirus and adeno-associated virus vectors. (See, e.g., Miller, A. D. (1990) Blood 76:271; Ausubel, supra; Uckert, W. and W. Walther (1994) Pharmacol. Ther. 63(3):323-347.) Other gene delivery mechanisms include liposome-derived systems, artificial viral envelopes, and other systems known in the art. (See, e.g., Rossi, J. J. (1995) Br. Med. Bull. 51(l):217-225; Boado, R. J. et al. (1998) J. Pharm. Sci. 87(11):1308-1315; and Morris, M. C. et al. (1997) Nucleic Acids Res. 25(14):2730-2736.)  
       [0195] In another embodiment of the invention, polynucleotides encoding MDDT may be used for somatic or germline gene therapy. Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe combined immunodeficiency (SCID)-X1 disease characterized by X-linked inheritance (Cavazzana-Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R. M. et al. (1995) Science 270:475-480; Bordignon, C. et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216; Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:667-703), thalassamias, familial hypercholesterolemia, and hemophilia resulting from Factor VIII or Factor IX deficiencies (Crystal, R. G. (1995) Science 270:404410; Verma, I. M. and N. Somia (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene product (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human immunodeficiency virus (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA. 93:11395-11399), hepatitis B or C virus (HBV, HCV); fungal parasites, such as  Candida albicans  and  Paracoccidioides brasiliensis ; and protozoan parasites such as  Plasmodium falciparum  and  Trypanosoma cruzi ). In the case where a genetic deficiency in MDDT expression or regulation causes disease, the expression of MDDT from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.  
       [0196] In a further embodiment of the invention, diseases or disorders caused by deficiencies in MDDT are treated by constructing mammalian expression vectors encoding MDDT and introducing these vectors by mechanical means into MDDT-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold particle delivery, (iii) liposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use of DNA transposons (Morgan, R. A. and W. F. Anderson (1993) Annu. Rev. Biochem. 62:191-217; Ivics, Z. (1997) Cell 91:501-510; Boulay, J-L. and H. Récipon (1998) Curr. Opin. Biotechnol. 9:445450).  
       [0197] Expression vectors that may be effective for the expression of MDDT include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX, PCR2-TOPOTA vectors (Invitrogen, Carlsbad Calif.), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla Calif.), and PTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto Calif.). MDDT may be expressed using (i) a constitutively active promoter, (e.g., from cytomegaloviris (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an inducible promoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H. Bujard (1992) Proc. Natl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al. (1995) Science 268:1766-1769; Rossi, F. M. V. and H. M. Blau (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX plasmid (Invitrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F. M. V. and H. M. Blau, supra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding MDDT from a normal individual.  
       [0198] Commercially available liposome transformation kits (e.g., the PERFECT LIPID TRANSFECTION KIT, available from Invitrogen) allow one with ordinary skill in the art to deliver polynucleotides to target cells in culture and require minimal effort to optimize experimental parameters. In the alternative, transformation is performed using the calcium phosphate method (Graham, F. L. and A. J. Eb (1973) Virology 52:456-467), or by electroporation (Neumann, E. et al. (1982) EMBO J. 1:841-845). The introduction of DNA to primary cells requires modification of these standardized mammalian transfection protocols.  
       [0199] In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to MDDT expression are treated by constructing a retrovirus vector consisting of (i) the polynucleotide encoding MDDT under the control of an independent promoter or the retrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE) along with additional retrovirus cis-acting RNA sequences and coding sequences required for efficient vector propagation. Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available (Stratagene) and are based on published data (Riviere, L et al. (1995) Proc. Natl. Acad. Sci. USA 92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells or a promiscuous envelope protein such as VSVg (Armentano, D. et al. (1987) J. Virol. 61:1647-1650; Bender, M. A. et al. (1987) J. Virol. 61:1639-1646; Adam, M. A. and A. D. Miller (1988) J. Virol. 62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey, R. et al. (1998) J. Virol. 72:9873-9880). U.S. Pat. No. 5,910,434 to Rigg (“Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant”) discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference. Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4 + T-cells), and the return of transduced cells to a patient are procedures well known to persons skilled in the art of gene therapy and have been well documented (Ranga, U. et al. (1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi, M. L. (1997) J. Virol. 71:47074716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997) Blood 89:2283-2290).  
       [0200] In the alternative, an adenovirus-based gene therapy delivery system is used to deliver polynucleotides encoding MDDT to cells which have one or more genetic abnormalities with respect to the expression of MDDT. The construction and packaging of adenovirus-based vectors are well known to those with ordinary skill in the art. Replication defective adenovirus vectors have proven to be versatile for importing genes encoding immunoregulatory proteins into intact islets in the pancreas (Csete, M. E. et al. (1995) Transplantation 27:263-268). Potentially useful adenoviral vectors are described in U.S. Pat. No. 5,707,618 to Armentano (“Adenovirus vectors for gene therapy”), hereby incorporated by reference. For adenoviral vectors, see also Antinozzi, P. A. et al. (1999) Annu. Rev. Nutr. 19:511-544 and Verma, I. M. and N. Somia (1997) Nature 18:389:239-242, both incorporated by reference herein.  
       [0201] In another alternative, a herpes-based, gene therapy delivery system is used to deliver polynucleotides encoding MDDT to target cells which have one or more genetic abnormalities with respect to the expression of MDDT. The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing MDDT to cells of the central nervous system, for which HSV has a tropism. The construction and packaging of herpes-based vectors are well known to those with ordinary skill in the art. A replication-competent herpes simplex virus (HSV) type 1-based vector has been used to deliver a reporter gene to the eyes of primates (Liu, X. et al. (1999) Exp. Eye Res. 169:385-395). The construction of a HSV-1 virus vector has also been disclosed in detail in U.S. Pat. No. 5,804,413 to DeLuca (“Herpes simplex virus strains for gene transfer”), which is hereby incorporated by reference. U.S. Pat. No. 5,804,413 teaches the use of recombinant HSV d92 which consists of a genome containing at least one exogenous gene to be transferred to a cell under the control of the appropriate promoter for purposes including human gene therapy. Also taught by this patent are the construction and use of recombinant HSV strains deleted for ICP4, ICP27 and ICP22. For HSV vectors, see also Goins, W. F. et al. (1999) J. Virol. 73:519-532 and Xu, H. et al. (1994) Dev. Biol. 163:152-161, hereby incorporated by reference. The manipulation of cloned herpesvirus sequences, the generation of recombinant virus following the transfection of multiple plasmids containing different segments of the large herpesvirus genomes, the growth and propagation of herpesvirus, and the infection of cells with herpesvirus are techniques well known to those of ordinary skill in the art.  
       [0202] In another alternative, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver polynucleotides encoding MDDT to target cells. The biology of the prototypic alphavirus, Semliki Forest Virus (SFV), has been studied extensively and gene transfer vectors have been based on the SFV genome (Garoff, H. and K. -J. Li (1998) Curr. Opin. Biotechnol. 9:464-469). During alphavirus RNA replication, a subgenomic RNA is generated that normally encodes the viral capsid proteins. This subgenomic RNA replicates to higher levels than the full length genomic RNA, resulting in the overproduction of capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase). Similarly, inserting the coding sequence for MDDT into the alphavirus genome in place of the capsid-coding region results in the production of a large number of MDDT-coding RNAs and the synthesis of high levels of MDDT in vector transduced cells. While alphavirus infection is typically associated with cell lysis within a few days, the ability to establish a persistent infection in hamster normal kidney cells (BHK-21) with a variant of Sindbis virus (SIN) indicates that the lytic replication of alphaviruses can be altered to suit the needs of the gene therapy application (Dryga, S. A. et al. (1997) Virology 228:74-83). The wide host range of alphaviruses will allow the introduction of MDDT into a variety of cell types. The specific transduction of a subset of cells in a population may require the sorting of cells prior to transduction. The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavirus cDNA and RNA transfections, and performing alphavirus infections, are well known to those with ordinary skill in the art.  
       [0203] Oligonucleotides derived from the transcription initiation site, e.g., between about positions −10 and +10 from the start site, may also be employed to inhibit gene expression. Similarly, inhibition can be achieved using triple helix base-pairing methodology. Triple helix pairing is useful because it causes inhibition of the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the literature. (See, e.g., Gee, J. E. et al. (1994) in Huber, B. E. and B. I. Carr,  Molecular and Immunologic Approaches , Futura Publishing, Mt. Kisco N.Y., pp. 163-177.) A complementary sequence or antisense molecule may also be designed to block translation of mRNA by preventing the transcript from binding to ribosomes.  
       [0204] Ribozymes, enzymatic RNA molecules, may also be used to catalyze the specific cleavage of RNA. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage. For example, engineered hammerhead motif ribozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of sequences encoding MDDT.  
       [0205] Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the following sequences: GUA, GUU, and GUC. Once identified, short RNA sequences of between 15 and 20 ribonucleotides, corresponding to the region of the target gene containing the cleavage site, may be evaluated for secondary structural features which may render the oligonucleotide inoperable. The suitability of candidate targets may also be evaluated by testing accessibility to hybridization with complementary oligonucleotides using ribonuclease protection assays.  
       [0206] Complementary ribonucleic acid molecules and ribozymes of the invention may be prepared by any method known in the art for the synthesis of nucleic acid molecules. These include techniques for chemically synthesizing oligonucleotides such as solid phase phosphoramidite chemical synthesis. Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA sequences encoding MDDT. Such DNA sequences may be incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6. Alternatively, these cDNA constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.  
       [0207] RNA molecules may be modified to increase intracellular stability and half-life. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5′ and/or 3′ ends of the molecule, or the use of phosphorothioate or 2′ O-methyl rather than phosphodiesterase linkages within the backbone of the molecule. This concept is inherent in the production of PNAs and can be extended in all of these molecules by the inclusion of nontraditional bases such as inosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-, and similarly modified forms of adenine, cytidine, guanine, thymine, and uridine which are not as easily recognized by endogenous endonucleases.  
       [0208] An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding MDDT. Compounds which may be effective in altering expression of a specific polynucleotide may include, but are not limited to, oligonucleotides, antisense oligonucleotides, triple helix-forming oligonucleotides, transcription factors and other polypeptide transcriptional regulators, and non-macromolecular chemical entities which are capable of interacting with specific polynucleotide sequences. Effective compounds may alter polynucleotide expression by acting as either inhibitors or promoters of polynucleotide expression. Thus, in the treatment of disorders associated with increased MDDT expression or activity, a compound which specifically inhibits expression of the polynucleotide encoding MDDT may be therapeutically useful, and in the treatment of disorders associated with decreased MDDT expression or activity, a compound which specifically promotes expression of the polynucleotide encoding MDDT may be therapeutically useful.  
       [0209] At least one, and up to a plurality, of test compounds may be screened for effectiveness in altering expression of a specific polynucleotide. A test compound may be obtained by any method commonly known in the art, including chemical modification of a compound known to be effective in altering polynucleotide expression; selection from an existing, commercially-available or proprietary library of naturally-occurring or non-natural chemical compounds; rational design of a compound based on chemical and/or structural properties of the target polynucleotide; and selection from a library of chemical compounds created combinatorially or randomly. A sample comprising a polynucleotide encoding MDDT is exposed to at least one test compound thus obtained. The sample may comprise, for example, an intact or permeabilized cell, or an in vitro cell-free or reconstituted biochemical system. Alterations in the expression of a polynucleotide encoding MDDT are assayed by any method commonly known in the art Typically, the expression of a specific nucleotide is detected by hybridization with a probe having a nucleotide sequence complementary to the sequence of the polynucleotide encoding MDDT. The amount of hybridization may be quantified, thus forming the basis for a comparison of the expression of the polynucleotide both with and without exposure to one or more test compounds. Detection of a change in the expression of a polynucleotide exposed to a test compound indicates that the test compound is effective in altering the expression of the polynucleotide. A screen for a compound effective in altering expression of a specific polynucleotide can be carried out, for example, using a  Schizosaccharomyces pombe  gene expression system (Atkins, D. et al. (1999) U.S. Pat. No. 5,932,435; Arndt, G. M. et al. (2000) Nucleic Acids Res. 28:E15) or a human cell line such as HeLa cell (Clarke, M. L. et al. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particular embodiment of the present invention involves screening a combinatorial library of oligonucleotides (such as deoxyribonucleotides, ribonucleotides, peptide nucleic acids, and modified oligonucleotides) for antisense activity against a specific polynucleotide sequence (Bruice, T. W. et al. (1997) U.S. Pat. No. 5,686,242; Bruice, T. W. et al. (2000) U.S. Pat. No. 6,022,691).  
       [0210] Many methods for introducing vectors into cells or tissues are available and equally suitable for use in vivo, in vitro, and ex vivo. For ex vivo therapy, vectors may be introduced into stem cells taken from the patient and clonally propagated for autologous transplant back into that same patient. Delivery by transfection, by liposome injections, or by polycationic amino polymers may be achieved using methods which are well known in the art. (See, e.g., Goldman, C. K. et al. (1997) Nat. Biotechnol. 15:462-466.)  
       [0211] Any of the therapeutic methods described above may be applied to any subject in need of such therapy, including, for example, mammals such as humans, dogs, cats, cows, horses, rabbits, and monkeys.  
       [0212] An additional embodiment of the invention relates to the administration of a composition which generally comprises an active ingredient formulated with a pharmaceutically acceptable excipient. Excipients may include, for example, sugars, starches, celluloses, gums, and proteins. Various formulations are commonly known and are thoroughly discussed in the latest edition of  Remington&#39;s Pharmaceutical Sciences  (Maack Publishing, Easton Pa.). Such compositions may consist of MDDT, antibodies to MDDT, and mimetics, agonists, antagonists, or inhibitors of MDDT.  
       [0213] The compositions utilized in this invention may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal means.  
       [0214] Compositions for pulmonary administration may be prepared in liquid or dry powder form. These compositions are generally aerosolized immediately prior to inhalation by the patient. In the case of small molecules (e.g. traditional low molecular weight organic drugs), aerosol delivery of fast-acting formulations is well-known in the art. In the case of macromolecules (e.g. larger peptides and proteins), recent developments in the field of pulmonary delivery via the alveolar region of the lung have enabled the practical delivery of drugs such as insulin to blood circulation (see, e.g., Patton, J. S. et al., U.S. Pat. No. 5,997,848). Pulmonary delivery has the advantage of administration without needle injection, and obviates the need for potentially toxic penetration enhancers.  
       [0215] Compositions suitable for use in the invention include compositions wherein the active ingredients are contained in an effective amount to achieve the intended purpose. The determination of an effective dose is well within the capability of those skilled in the art.  
       [0216] Specialized forms of compositions may be prepared for direct intracellular delivery of macromolecules comprising MDDT or fragments thereof. For example, liposome preparations containing a cell-impermeable macromolecule may promote cell fusion and intracellular delivery of the macromolecule. Alternatively, MDDT or a fragment thereof may be joined to a short cationic N-terminal portion from the HIV Tat-1 protein. Fusion proteins thus generated have been found to transduce into the cells of all tissues, including the brain, in a mouse model system (Schwarze, S. R. et al. (1999) Science 285:1569-1572).  
       [0217] For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays, e.g., of neoplastic cells, or in animal models such as mice, rats, rabbits, dogs, monkeys, or pigs. An animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.  
       [0218] A therapeutically effective dose refers to that amount of active ingredient, for example MDDT or fragments thereof, antibodies of MDDT, and agonists, antagonists or inhibitors of MDDT, which ameliorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell cultures or with experimental animals, such as by calculating the ED 50  (the dose therapeutically effective in 50% of the population) or LD 50  (the dose lethal to 50% of the population) statistics. The dose ratio of toxic to therapeutic effects is the therapeutic index, which can be expressed as the LD 50 /ED 50  ratio. Compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies are used to formulate a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that includes the ED 50  with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, the sensitivity of the patient, and the route of administration.  
       [0219] The exact dosage will be determined by the practitioner, in light of factors related to the subject requiring treatment. Dosage and administration are adjusted to provide sufficient levels of the active moiety or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, the general health of the subject, the age, weight, and gender of the subject, time and frequency of administration, drug combination(s), reaction sensitivities, and response to therapy. Long-acting compositions may be administered every 3 to 4 days, every week, or biweekly depending on the half-life and clearance rate of the particular formulation.  
       [0220] Normal dosage amounts may vary from about 0.1 μg to 100,000 μg, up to a total dose of about 1 gram, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art. Those skilled in the art will employ different formulations for nucleotides than for proteins or their inhibitors. Similarly, delivery of polynucleotides or polypeptides will be specific to particular cells, conditions, locations, etc.  
       [0221] Diagnostics  
       [0222] In another embodiment, antibodies which specifically bind MDDT may be used for the diagnosis of disorders characterized by expression of MDDT, or in assays to monitor patients being treated with MDDT or agonists, antagonists, or inhibitors of MDDT. Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics. Diagnostic assays for MDDT include methods which utilize the antibody and a label to detect MDDT in human body fluids or in extracts of cells or tissues. The antibodies may be used with or without modification, and may be labeled by covalent or non-covalent attachment of a reporter molecule. A wide variety of reporter molecules, several of which are described above, are known in the art and may be used.  
       [0223] A variety of protocols for measuring MDDT, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of MDDT expression. Normal or standard values for MDDT expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example, human subjects, with antibodies to MDDT under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of MDDT expressed in subject, control, and disease samples from biopsied tissues are compared with the standard values. Deviation between standard and subject values establishes the parameters for diagnosing disease.  
       [0224] In another embodiment of the invention, the polynucleotides encoding MDDT may be used for diagnostic purposes. The polynucleotides which may be used include oligonucleotide sequences, complementary RNA and DNA molecules, and PNAs. The polynucleotides may be used to detect and quantify gene expression in biopsied tissues in which expression of MDDT may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of MDDT, and to monitor regulation of MDDT levels during therapeutic intervention.  
       [0225] In one aspect, hybridization with PCR probes which are capable of detecting polynucleotide sequences, including genomic sequences, encoding MDDT or closely related molecules may be used to identify nucleic acid sequences which encode MDDT. The specificity of the probe, whether it is made from a highly specific region, e.g., the 5′ regulatory region, or from a less specific region, e.g., a conserved motif, and the stringency of the hybridization or amplification will determine whether the probe identifies only naturally occurring sequences encoding MDDT, allelic variants, or related sequences.  
       [0226] Probes may also be used for the detection of related sequences, and may have at least 50% sequence identity to any of the MDDT encoding sequences. The hybridization probes of the subject invention may be DNA or RNA and may be derived from the sequence of SEQ ID NO:13-24 or from genomic sequences including promoters, enhancers, and introns of the MDDT gene.  
       [0227] Means for producing specific hybridization probes for DNAs encoding MDDT include the cloning of polynucleotide sequences encoding MDDT or MDDT derivatives into vectors for the production of mRNA probes. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by means of the addition of the appropriate RNA polymerases and the appropriate labeled nucleotides. Hybridization probes may be labeled by a variety of reporter groups, for example, by radionuclides such as  32 P or  35 S, or by enzymatic labels, such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems, and the like.  
       [0228] Polynucleotide sequences encoding MDDT may be used for the diagnosis of disorders associated with expression of MDDT. Examples of such disorders include, but are not limited to, a developmental disorder such as renal tubular acidosis, anemia, Cushing&#39;s syndrome, achondroplastic dwarfism, Duchenne and Becker muscular dystrophy, epilepsy, gonadal dysgenesis, WAGR syndrome (Wilms&#39; tumor, aniridia, genitourinary abnormalities, and mental retardation), Smith-Magenis syndrome, myelodysplastic syndrome, hereditary mucoepithelial dysplasia, hereditary keratodermas, hereditary neuropathies such as Charcot-Marie-Tooth disease and neurofibromatosis, hypothyroidism, hydrocephalus, a seizure disorder such as Syndenham&#39;s chorea and cerebral palsy, spina bifida, anencephaly, craniorachischisis, congenital glaucoma, cataract, and sensorineural hearing loss; a cell proliferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, a cancer of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus; and an immunological disorder such as inflammation, actinic keratosis, acquired immunodeficiency syndrome (AIDS), Addison&#39;s disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, arteriosclerosis, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, bronchitis, bursitis, cholecystitis, cirrhosis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture&#39;s syndrome, gout, Graves&#39; disease, Hashimoto&#39;s thyroiditis, paroxysmal nocturnal hemoglobinuria, hepatitis, hypereosinophilia, irritable bowel syndrome, episodic lymphopenia with lymphocytotoxins, mixed connective tissue disease (MCTD), multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, myelofibrosis, osteoarthritis, osteoporosis, pancreatitis, polycythemia vera, polymyositis, psoriasis, Reiter&#39;s syndrome, rheumatoid arthritis, scleroderma, Sjögren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, primary thrombocythemia, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, trauma, and hematopoietic cancer including lymphoma, leukemia, and myeloma. The polynucleotide sequences encoding MDDT may be used in Southern or northern analysis, dot blot, or other membrane-based technologies; in PCR technologies; in dipstick, pin, and multiformat ELISA-like assays; and in microarrays utilizing fluids or tissues from patients to detect altered MDDT expression. Such qualitative or quantitative methods are well known in the art.  
       [0229] In a particular aspect, the nucleotide sequences encoding MDDT may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding MDDT may be labeled by standard methods and added to a fluid or tissue sample from a patient under conditions suitable for the formation of hybridization complexes. After a suitable incubation period, the sample is washed and the signal is quantified and compared with a standard value. If the amount of signal in the patient sample is significantly altered in comparison to a control sample then the presence of altered levels of nucleotide sequences encoding MDDT in the sample indicates the presence of the associated disorder. Such assays may also be used to evaluate the efficacy of a particular therapeutic treatment regimen in animal studies, in clinical trials, or to monitor the treatment of an individual patient.  
       [0230] In order to provide a basis for the diagnosis of a disorder associated with expression of MDDT, a normal or standard profile for expression is established. This may be accomplished by combining body fluids or cell extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding MDDT, under conditions suitable for hybridization or amplification. Standard hybridization may be quantified by comparing the values obtained from normal subjects with values from an experiment in which a known amount of a substantially purified polynucleotide is used. Standard values obtained in this manner may be compared with values obtained from samples from patients who are symptomatic for a disorder. Deviation from standard values is used to establish the presence of a disorder.  
       [0231] Once the presence of a disorder is established and a treatment protocol is initiated, hybridization assays may be repeated on a regular basis to determine if the level of expression in the patient begins to approximate that which is observed in the normal subject. The results obtained from successive assays may be used to show the efficacy of treatment over a period ranging from several days to months.  
       [0232] With respect to cancer, the presence of an abnormal amount of transcript (either under- or overexpressed) in biopsied tissue from an individual may indicate a predisposition for the development of the disease, or may provide a means for detecting the disease prior to the appearance of actual clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier thereby preventing the development or further progression of the cancer.  
       [0233] Additional diagnostic uses for oligonucleotides designed from the sequences encoding MDDT may involve the use of PCR. These oligomers may be chemically synthesized, generated enzymatically, or produced in vitro. Oligomers will preferably contain a fragment of a polynucleotide encoding MDDT, or a fragment of a polynucleotide complementary to the polynucleotide encoding MDDT, and will be employed under optimized conditions for identification of a specific gene or condition. Oligomers may also be employed under less stringent conditions for detection or quantification of closely related DNA or RNA sequences.  
       [0234] In a particular aspect, oligonucleotide primers derived from the polynucleotide sequences encoding MDDT may be used to detect single nucleotide polymorphisms (SNPs). SNPs are substitutions, insertions and deletions that are a frequent cause of inherited or acquired genetic disease in humans. Methods of SNP detection include, but are not limited to, single-stranded conformation polymorphism (SSCP) and fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from the polynucleotide sequences encoding MDDT are used to amplify DNA using the polymerase chain reaction (PCR). The DNA may be derived, for example, from diseased or normal tissue, biopsy samples, bodily fluids, and the like. SNPs in the DNA cause differences in the secondary and tertiary structures of PCR products in single-stranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In fSCCP, the oligonucleotide primers are fluorescently labeled, which allows detection of the amplimers in high-throughput equipment such as DNA sequencing machines. Additionally, sequence database analysis methods, termed in silico SNP (isSNP), are capable of identifying polymorphisms by comparing the sequence of individual overlapping DNA fragments which assemble into a common consensus sequence. These computer-based methods filter out sequence variations due to laboratory preparation of DNA and sequencing errors using statistical models and automated analyses of DNA sequence chromatograms. In the alternative, SNPs may be detected and characterized by mass spectrometry using, for example, the high throughput MASSARRAY system (Sequenom, Inc., San Diego Calif.).  
       [0235] Methods which may also be used to quantify the expression of MDDT include radiolabeling or biotinylating nucleotides, coamplification of a control nucleic acid, and interpolating results from standard curves. (See, e.g., Melby, P. C. et al. (1993) J. Immunol. Methods 159:235-244; Duplaa, C. et al. (1993) Anal. Biochem. 212:229-236.) The speed of quantitation of multiple samples may be accelerated by running the assay in a high-throughput format where the oligomer or polynucleotide of interest is presented in various dilutions and a spectrophotometric or colorimetric response gives rapid quantitation.  
       [0236] In further embodiments, oligonucleotides or longer fragments derived from any of the polynucleotide sequences described herein may be used as elements on a microarray. The microarray can be used in transcript imaging techniques which monitor the relative expression levels of large numbers of genes simultaneously as described below. The microarray may also be used to identify genetic variants, mutations, and polymorphisms. This information may be used to determine gene function, to understand the genetic basis of a disorder, to diagnose a disorder, to monitor progression/regression of disease as a function of gene expression, and to develop and monitor the activities of therapeutic agents in the treatment of disease. In particular, this information may be used to develop a pharmacogenomic profile of a patient in order to select the most appropriate and effective treatment regimen for that patient. For example, therapeutic agents which are highly effective and display the fewest side effects may be selected for a patient based on his/her pharmacogenomic profile.  
       [0237] In another embodiment, MDDT, fragments of MDDT, or antibodies specific for MDDT may be used as elements on a microarray. The microarray may be used to monitor or measure protein-protein interactions, drug-target interactions, and gene expression profiles, as described above.  
       [0238] A particular embodiment relates to the use of the polynucleotides of the present invention to generate a transcript image of a tissue or cell type. A transcript image represents the global pattern of gene expression by a particular tissue or cell type. Global gene expression patterns are analyzed by quantifying the number of expressed genes and their relative abundance under given conditions and at a given time. (See Seilhamer et al., “Comparative Gene Transcript Analysis,” U.S. Pat. No. 5,840,484, expressly incorporated by reference herein.) Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totality of transcripts or reverse transcripts of a particular tissue or cell type. In one embodiment, the hybridization takes place in high-throughput format, wherein the polynucleotides of the present invention or their complements comprise a subset of a plurality of elements on a microarray. The resultant transcript image would provide a profile of gene activity.  
       [0239] Transcript images may be generated using transcripts isolated from tissues, cell lines, biopsies, or other biological samples. The transcript image may thus reflect gene expression in vivo, as in the case of a tissue or biopsy sample, or in vitro, as in the case of a cell line.  
       [0240] Transcript images which profile the expression of the polynucleotides of the present invention may also be used in conjunction with in vitro model systems and preclinical evaluation of pharmaceuticals, as well as toxicological testing of industrial and naturally-occurring environmental compounds. All compounds induce characteristic gene expression patterns, frequently termed molecular fingerprints or toxicant signatures, which are indicative of mechanisms of action and toxicity (Nuwaysir, E. F. et al. (1999) Mol. Carcinog. 24:153-159; Steiner, S. and N. L. Anderson (2000) Toxicol. Lett. 112-113:467-471, expressly incorporated by reference herein). If a test compound has a signature similar to that of a compound with known toxicity, it is likely to share those toxic properties. These fingerprints or signatures are most useful and refined when they contain expression information from a large number of genes and gene families. Ideally, a genome-wide measurement of expression provides the highest quality signature. Even genes whose expression is not altered by any tested compounds are important as well, as the levels of expression of these genes are used to normalize the rest of the expression data. The normalization procedure is useful for comparison of expression data after treatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in interpretation of toxicity mechanisms, knowledge of gene function is not necessary for the statistical matching of signatures which leads to prediction of toxicity. (See, for example, Press Release 00-02 from the National Institute of Environmental Health Sciences, released Feb. 29, 2000, available at http://www.niehs.nih.gov/oc/news/toxchip.htm) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include all expressed gene sequences.  
       [0241] In one embodiment, the toxicity of a test compound is assessed by treating a biological sample containing nucleic acids with the test compound. Nucleic acids that are expressed in the treated biological sample are hybridized with one or more probes specific to the polynucleotides of the present invention, so that transcript levels corresponding to the polynucleotides of the present invention may be quantified. The transcript levels in the treated biological sample are compared with levels in an untreated biological sample. Differences in the transcript levels between the two samples are indicative of a toxic response caused by the test compound in the treated sample.  
       [0242] Another particular embodiment relates to the use of the polypeptide sequences of the present invention to analyze the proteome of a tissue or cell type. The term proteome refers to the global pattern of protein expression in a particular tissue or cell type. Each protein component of a proteome can be subjected individually to further analysis. Proteome expression patterns, or profiles, are analyzed by quantifying the number of expressed proteins and their relative abundance under given conditions and at a given time. A profile of a cell&#39;s proteome may thus be generated by separating and analyzing the polypeptides of a particular tissue or cell type. In one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelectric focusing in the first dimension, and then according to molecular weight by sodium dodecyl sulfate slab gel electrophoresis in the second dimension (Steiner and Anderson, supra). The proteins are visualized in the gel as discrete and uniquely positioned spots, typically by staining the gel with an agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generally proportional to the level of the protein in the sample. The optical densities of equivalently positioned protein spots from different samples, for example, from biological samples either treated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the treatment. The proteins in the spots are partially sequenced using, for example, standard methods employing chemical or enzymatic cleavage followed by mass spectrometry. The identity of the protein in a spot may be determined by comparing its partial sequence, preferably of at least 5 contiguous amino acid residues, to the polypeptide sequences of the present invention. In some cases, further sequence data may be obtained for definitive protein identification.  
       [0243] A proteomic profile may also be generated using antibodies specific for MDDT to quantify the levels of MDDT expression. In one embodiment, the antibodies are used as elements on a microarray, and protein expression levels are quantified by exposing the microarray to the sample and detecting the levels of protein bound to each array element (Lueking, A. et al. (1999) Anal. Biochem. 270:103-111; Mendoze, L. G. et al. (1999) Biotechniques 27:778-788). Detection may be performed by a variety of methods known in the art, for example, by reacting the proteins in the sample with a thiol- or amino-reactive fluorescent compound and detecting the amount of fluorescence bound at each array element.  
       [0244] Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in parallel with toxicant signatures at the transcript level. There is a poor correlation between transcript and protein abundances for some proteins in some tissues (Anderson, N. L. and J. Seilhamer (1997) Electrophoresis 18:533-537), so proteome toxicant signatures may be useful in the analysis of compounds which do not significantly affect the transcript image, but which alter the proteomic profile. In addition, the analysis of transcripts in body fluids is difficult, due to rapid degradation of mRNA, so proteomic profiling may be more reliable and informative in such cases.  
       [0245] In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins that are expressed in the treated biological sample are separated so that the amount of each protein can be quantified. The amount of each protein is compared to the amount of the corresponding protein in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample. Individual proteins are identified by sequencing the amino acid residues of the individual proteins and comparing these partial sequences to the polypeptides of the present invention.  
       [0246] In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins from the biological sample are incubated with antibodies specific to the polypeptides of the present invention. The amount of protein recognized by the antibodies is quantified. The amount of protein in the treated biological sample is compared with the amount in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample.  
       [0247] Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., Brennan, T. M. et al. (1995) U.S. Pat. No. 5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application WO95/251116; Shalon, D. et al. (1995) PCT application WO95/35505; Heller, R. A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; and Heller, M. J. et al. (1997) U.S. Pat. No. 5,605,662.) Various types of microarrays are well known and thoroughly described in  DNA Microarrays: A Practical Approach , M. Schena, ed. (1999) Oxford University Press, London, hereby expressly incorporated by reference.  
       [0248] In another embodiment of the invention, nucleic acid sequences encoding MDDT may be used to generate hybridization probes useful in mapping the naturally occurring genomic sequence. Either coding or noncoding sequences may be used, and in some instances, noncoding sequences may be preferable over coding sequences. For example, conservation of a coding sequence among members of a multi-gene family may potentially cause undesired cross hybridization during chromosomal mapping. The sequences may be mapped to a particular chromosome, to a specific region of a chromosome, or to artificial chromosome constructions, e.g., human artificial chromosomes (HACs), yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), bacterial P1 constructions, or single chromosome cDNA libraries. (See, e.g., Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355; Price, C. M. (1993) Blood Rev. 7:127-134; and Trask, B. J. (1991) Trends Genet. 7:149-154.) Once mapped, the nucleic acid sequences of the invention may be used to develop genetic linkage maps, for example, which correlate the inheritance of a disease state with the inheritance of a particular chromosome region or restriction fragment length polymorphism (RFLP). (See, for example, Lander, E. S. and D. Botstein (1986) Proc. Natl. Acad. Sci. USA 83:7353-7357.)  
       [0249] Fluorescent in situ hybridization (FISH) may be correlated with other physical and genetic map data. (See, e.g., Heinz-Ulrich, et al. (1995) in Meyers, supra, pp. 965-968.) Examples of genetic map data can be found in various scientific journals or at the Online Mendelian Inheritance in Man (OMIM) World Wide Web site. Correlation between the location of the gene encoding MDDT on a physical map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA associated with that disorder and thus may further positional cloning efforts.  
       [0250] In situ hybridization of chromosomal preparations and physical mapping techniques, such as linkage analysis using established chromosomal markers, may be used for extending genetic maps. Often the placement of a gene on the chromosome of another mammalian species, such as mouse, may reveal associated markers even if the exact chromosomal locus is not known. This information is valuable to investigators searching for disease genes using positional cloning or other gene discovery techniques. Once the gene or genes responsible for a disease or syndrome have been crudely localized by genetic linkage to a particular genomic region, e.g., ataxia-telangiectasia to 11q22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation. (See, e.g., Gatti, R. A. et al. (1988) Nature 336:577-580.) The nucleotide sequence of the instant invention may also be used to detect differences in the chromosomal location due to translocation, inversion, etc., among normal, carrier, or affected individuals.  
       [0251] In another embodiment of the invention, MDDT, its catalytic or immunogenic fragments, or oligopeptides thereof can be used for screening libraries of compounds in any of a variety of drug screening techniques. The fragment employed in such screening may be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. The formation of binding complexes between MDDT and the agent being tested may be measured.  
       [0252] Another technique for drug screening provides for high throughput screening of compounds having suitable binding affinity to the protein of interest. (See, e.g., Geysen, et al. (1984) PCT application WO84/03564.) In this method, large numbers of different small test compounds are synthesized on a solid substrate. The test compounds are reacted with MDDT, or fragments thereof, and washed. Bound MDDT is then detected by methods well known in the art. Purified MDDT can also be coated directly onto plates for use in the aforementioned drug screening techniques. Alternatively, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support.  
       [0253] In another embodiment, one may use competitive drug screening assays in which neutralizing antibodies capable of binding MDDT specifically compete with a test compound for binding MDDT. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with MDDT.  
       [0254] In additional embodiments, the nucleotide sequences which encode MDDT may be used in any molecular biology techniques that have yet to be developed, provided the new techniques rely on properties of nucleotide sequences that are currently known, including, but not limited to, such properties as the triplet genetic code and specific base pair interactions.  
       [0255] Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.  
       [0256] The disclosures of all patents, applications and publications, mentioned above and below, including U.S. Ser. No. 60/251,791, are expressly incorporated by reference herein. 
     
    
    
     EXAMPLES  
     [0257] I. Construction of cDNA Libraries  
     [0258] Incyte cDNAs were derived from cDNA libraries described in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.) and shown in Table 4, column 5. Some tissues were homogenized and lysed in guanidinium isothiocyanate, while others were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL (Life Technologies), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates were centrifuged over CsCl cushions or extracted with chloroform. RNA was precipitated from the lysates with either isopropanol or sodium acetate and ethanol, or by other routine methods.  
     [0259] Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA purity. In some cases, RNA was treated with DNase. For most libraries, poly(A)+RNA was isolated using oligo d(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles (QIAGEN, Chatsworth Calif.), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Austin Tex.).  
     [0260] In some cases, Stratagene was provided with RNA and constructed the corresponding cDNA libraries. Otherwise, cDNA was synthesized and cDNA libraries were constructed with the UNIZAP vector system (Stratagene) or SUPERSCRIT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription was initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters were ligated to double stranded cDNA, and the cDNA was digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA was size-selected (300-1000 bp) using SEPHACRYL S1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1 plasmid (Life Technologies), PCDNA2.1 plasmid (Invitrogen, Carlsbad Calif.), PBK-CMV plasmid (Stratagene), PCR2-TOPOTA plasmid (Invitrogen), PCMV-ICIS plasmid (Stratagene), pIGEN (Incyte Genomics, Palo Alto Calif.), pRARE (Incyte Genomics), or pINCY (Incyte Genomics), or derivatives thereof. Recombinant plasmids were transformed into competent  E. coli  cells including XL1-Blue, XL1-BlueMRF, or SOLR from Stratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies.  
     [0261] II. Isolation of cDNA Clones  
     [0262] Plasmids obtained as described in Example I were recovered from host cells by in vivo excision using the UNIZAP vector system (Stratagene) or by cell lysis. Plasmids were purified using at least one of the following: a Magic or WIZARD Minipreps DNA purification system (Promega); an AGTC Miniprep purification kit (Edge Biosystems, Gaithersburg Md.); and QIAWELL 8 Plasmid, QIAWELL 8 Plus Plasmid, QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification kit from QIAGEN. Following precipitation, plasmids were resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4° C.  
     [0263] Alternatively, plasmid DNA was amplified from host cell lysates using direct link PCR in a high-throughput format (Rao, V. B. (1994) Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps were carried out in a single reaction mixture. Samples were processed and stored in 384-well plates, and the concentration of amplified plasmid DNA was quantified fluorometrically using PICOGREEN dye (Molecular Probes, Eugene OR) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland).  
     [0264] III. Sequencing and Analysis  
     [0265] Incyte cDNA recovered in plasmids as described in Example II were sequenced as follows. Sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (Applied Biosystems) thermal cycler or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB 2200 (Hamilton) liquid transfer system cDNA sequencing reactions were prepared using reagents provided by Amersham Pharmacia Biotech or supplied in ABI sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems). Electrophoretic separation of cDNA sequencing reactions and detection of labeled polynucleotides were carried out using the MEGABACE 1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or 377 sequencing system (Applied Biosystems) in conjunction with standard ABI protocols and base calling software; or other sequence analysis systems known in the art. Reading frames within the cDNA sequences were identified using standard methods (reviewed in Ausubel, 1997, supra, unit 7.7). Some of the cDNA sequences were selected for extension using the techniques disclosed in Example VIII.  
     [0266] The polynucleotide sequences derived from Incyte cDNAs were validated by removing vector, linker, and poly(A) sequences and by masking ambiguous bases, using algorithms and programs based on BLAST, dynamic programming, and dinucleotide nearest neighbor analysis. The Incyte cDNA sequences or translations thereof were then queried against a selection of public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases, and BLOCKS, PRINTS, DOMO, PRODOM; PROTEOME databases with sequences from  Homo sapiens, Rattus norvegicus, Mus musculus, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe , and  Candida albicans  (Incyte Genomics, Palo Alto Calif.); and hidden Markov model (HMM)-based protein family databases such as PFAM. (HMM is a probabilistic approach which analyzes consensus primary structures of gene families. See, for example, Eddy, S. R. (1996) Curr. Opin. Struct. Biol. 6:361-365.) The queries were performed using programs based on BLAST, FASTA, BLIMPS, and HMMER. The Incyte cDNA sequences were assembled to produce full length polynucleotide sequences. Alternatively, GenBank cDNAs, GenBank ESTs, stitched sequences, stretched sequences, or Genscan-predicted coding sequences (see Examples IV and V) were used to extend Incyte cDNA assemblages to full length. Assembly was performed using programs based on Phred, Phrap, and Consed, and cDNA assemblages were screened for open reading frames using programs based on GeneMark, BLAST, and FASTA. The full length polynucleotide sequences were translated to derive the corresponding full length polypeptide sequences. Alternatively, a polypeptide of the invention may begin at any of the methionine residues of the full length translated polypeptide. Full length polypeptide sequences were subsequently analyzed by querying against databases such as the GenBank protein databases (genpept), SwissProt, the PROTEOME databases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, and hidden Markov model (HMM)-based protein family databases such as PFAM. Full length polynucleotide sequences are also analyzed using MACDNASIS PRO software (Hitachi Software Engineering, South San Francisco Calif.) and LASERGENE software (DNASTAR). Polynucleotide and polypeptide sequence alignments are generated using default parameters specified by the CLUSTAL algorithm as incorporated into the MEGALIGN multisequence alignment program (DNASTAR), which also calculates the percent identity between aligned sequences.  
     [0267] Table 7 summarizes the tools, programs, and algorithms used for the analysis and assembly of Incyte cDNA and full length sequences and provides applicable descriptions, references, and threshold parameters. The first column of Table 7 shows the tools, programs, and algorithms used, the second column provides brief descriptions thereof, the third column presents appropriate references, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score or the lower the probability value, the greater the identity between two sequences).  
     [0268] The programs described above for the assembly and analysis of full length polynucleotide and polypeptide sequences were also used to identify polynucleotide sequence fragments from SEQ ID NO:13-24. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies are described in Table 4, column 4.  
     [0269] IV. Identification and Editing of Coding Sequences from Genomic DNA  
     [0270] Putative full-length human molecules for disease detection and treatment were initially identified by running the Genscan gene identification program against public genomic sequence databases (e.g., gbpri and gbhtg). Genscan is a general-purpose gene identification program which analyzes genomic DNA sequences from a variety of organisms (See Burge, C. and S. Karlin (1997) J. Mol. Biol. 268:78-94, and Burge, C. and S. Karlin (1998) Curr. Opin. Struct. Biol. 8:346-354). The program concatenates predicted exons to form an assembled cDNA sequence extending from a methionine to a stop codon. The output of Genscan is a FASTA database of polynucleotide and polypeptide sequences. The maximum range of sequence for Genscan to analyze at once was set to 30 kb. To determine which of these Genscan predicted cDNA sequences encode full-length human molecules for disease detection and treatment, the encoded polypeptides were analyzed by querying against PFAM models for full-length human molecules for disease detection and treatment Potential full-length human molecules for disease detection and treatment were also identified by homology to Incyte cDNA sequences that had been annotated as full-length human molecules for disease detection and treatment. These selected Genscan-predicted sequences were then compared by BLAST analysis to the genpept and gbpri public databases. Where necessary, the Genscan-predicted sequences were then edited by comparison to the top BLAST hit from genpept to correct errors in the sequence predicted by Genscan, such as extra or omitted exons. BLAST analysis was also used to find any Incyte cDNA or public cDNA coverage of the Genscan-predicted sequences, thus providing evidence for transcription. When Incyte cDNA coverage was available, this information was used to correct or confirm the Genscan predicted sequence. Full length polynucleotide sequences were obtained by assembling Genscan-predicted coding sequences with Incyte cDNA sequences and/or public cDNA sequences using the assembly process described in Example III. Alternatively, full length polynucleotide sequences were derived entirely from edited or unedited Genscan-predicted coding sequences.  
     [0271] V. Assembly of Genomic Sequence Data with cDNA Sequence Data  
     [0272] “Stitched” Sequences  
     [0273] Partial cDNA sequences were extended with exons predicted by the Genscan gene identification program described in Example IV. Partial cDNAs assembled as described in Example III were mapped to genomic DNA and parsed into clusters containing related cDNAs and Genscan exon predictions from one or more genomic sequences. Each cluster was analyzed using an algorithm based on graph theory and dynamic programming to integrate cDNA and genomic information, generating possible splice variants that were subsequently confirmed, edited, or extended to create a full length sequence. Sequence intervals in which the entire length of the interval was present on more than one sequence in the cluster were identified, and intervals thus identified were considered to be equivalent by transitivity. For example, if an interval was present on a cDNA and two genomic sequences, then all three intervals were considered to be equivalent. This process allows unrelated but consecutive genomic sequences to be brought together, bridged by cDNA sequence. Intervals thus identified were then “stitched” together by the stitching algorithm in the order that they appear along their parent sequences to generate the longest possible sequence, as well as sequence variants. Linkages between intervals which proceed along one type of parent sequence (cDNA to cDNA or genomic sequence to genomic sequence) were given preference over linkages which change parent type (cDNA to genomic sequence). The resultant stitched sequences were translated and compared by BLAST analysis to the genpept and gbpri public databases. Incorrect exons predicted by Genscan were corrected by comparison to the top BLAST hit from genpept. Sequences were further extended with additional cDNA sequences, or by inspection of genomic DNA, when necessary.  
     [0274] “Stretched” Sequences  
     [0275] Partial DNA sequences were extended to full length with an algorithm based on BLAST analysis. First, partial cDNAs assembled as described in Example III were queried against public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases using the BLAST program The nearest GenBank protein homolog was then compared by BLAST analysis to either Incyte cDNA sequences or GenScan exon predicted sequences described in Example IV. A chimeric protein was generated by using the resultant high-scoring segment pairs (HSPs) to map the translated sequences onto the GenBank protein homolog. Insertions or deletions may occur in the chimeric protein with respect to the original GenBank protein homolog. The GenBank protein homolog, the chimeric protein, or both were used as probes to search for homologous genomic sequences from the public human genome databases. Partial DNA sequences were therefore “stretched” or extended by the addition of homologous genomic sequences. The resultant stretched sequences were examined to determine whether it contained a complete gene.  
     [0276] VI. Chromosomal Mapping of MDDT Encoding Polynucleotides  
     [0277] The sequences which were used to assemble SEQ ID NO:13-24 were compared with sequences from the Incyte LIFESEQ database and public domain databases using BLAST and other implementations of the Smith-Waterman algorithm. Sequences from these databases that matched SEQ ID NO:13-24 were assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as Phrap (Table 7). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Généthon were used to determine if any of the clustered sequences had been previously mapped. Inclusion of a mapped sequence in a cluster resulted in the assignment of all sequences of that cluster, including its particular SEQ ID NO:, to that map location.  
     [0278] Map locations are represented by ranges, or intervals, of human chromosomes. The map position of an interval, in centiMorgans, is measured relative to the terminus of the chromosome&#39;s p-arm. (The centiMorgan (cM) is a unit of measurement based on recombination frequencies between chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb) of DNA in humans, although this can vary widely due to hot and cold spots of recombination.) The cM distances are based on genetic markers mapped by Généthon which provide boundaries for radiation hybrid markers whose sequences were included in each of the clusters. Human genome maps and other resources available to the public, such as the NCBI “GeneMap&#39;99” World Wide Web site (http://www.ncbi.nlm.nih.gov/genemap/), can be employed to determine if previously identified disease genes map within or in proximity to the intervals indicated above.  
     [0279] In this manner, SEQ ID NO:13 was mapped to chromosome 1 within the interval from 173.9 to 196.0 centiMorgans. SEQ ID NO:16 was mapped to chromosome 10 within the interval from 81.7 to 88.6 centiMorgans. SEQ ID NO:18 was mapped to chromosome 9 within the interval from 50.3 to 75.8 centiMorgans and to chromosome 11 within the interval from 28.1 to 34.3 centiMorgans. SEQ ID NO:20 was mapped to chromosome 1 within the interval from 66.6 to 74.3 centiMorgans. SEQ ID NO:21 was mapped to chromosome 9 within the interval from 144.3 centiMorgans to the q terminus. SEQ ID NO:23 was mapped to chromosome 7 within the interval from 29.6 to 35 centiMorgans and to chromosome 9 within the interval from 96.3 to 104.9 centiMorgans. More than one map location is reported for SEQ ID NO:18 and SEQ ID NO:23, indicating that sequences having different map locations were assembled into a single cluster. This situation occurs, for example, when sequences having strong similarity, but not complete identity, are assembled into a single cluster.  
     [0280] VII. Analysis of Polynucleotide Expression  
     [0281] Northern analysis is a laboratory technique used to detect the presence of a transcript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular cell type or tissue have been bound. (See, e.g., Sambrook, supra, ch. 7; Ausubel 1995) supra, ch. 4 and 16.)  
     [0282] Analogous computer techniques applying BLAST were used to search for identical or related molecules in CDNA databases such as GenBank or LIFESEQ (Incyte Genomics). This analysis is much faster than multiple membrane-based hybridizations. In addition, the sensitivity of the computer search can be modified to determine whether any particular match is categorized as exact or similar. The basis of the search is the product score, which is defined as:  
     [0283] BLAST Score×Percent Identity/5×minimum {length(Seq. 1), length(Seq. 2)} 
     [0284] The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. The product score is a normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score of +5 for every base that matches in a high-scoring segment pair (HSP), and −4 for every mismatch. Two sequences may share more than one HSP (separated by gaps). If there is more than one HSP, then the pair with the highest BLAST score is used to calculate the product score. The product score represents a balance between fractional overlap and quality in a BLAST alignment. For example, a product score of 100 is produced only for 100% identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and 70% overlap at one end, or by 88% identity and 100% overlap at the other. A product score of 50 is produced either by 100% identity and 50% overlap at one end, or 79% identity and 100% overlap.  
     [0285] Alternatively, polynucleotide sequences encoding MDDT are analyzed with respect to the tissue sources from which they were derived. For example, some full length sequences are assembled, at least in part, with overlapping Incyte cDNA sequences (see Example III). Each cDNA sequence is derived from a cDNA library constructed from a human tissue. Each human tissue is classified into one of the following organ/tissue categories: cardiovascular system; connective tissue; digestive system; embryonic structures; endocrine system; exocrine glands; genitalia, female; genitalia, male; germ cells; hemic and immune system; liver; musculoskeletal system; nervous system; pancreas; respiratory system; sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. The number of libraries in each category is counted and divided by the total number of libraries across all categories. Similarly, each human tissue is classified into one of the following disease/condition categories: cancer, cell line, developmental, inflammation, neurological, trauma, cardiovascular, pooled, and other, and the number of libraries in each category is counted and divided by the total number of libraries across all categories. The resulting percentages reflect the tissue- and disease-specific expression of cDNA encoding MDDT. cDNA sequences and cDNA library/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.).  
     [0286] VIII. Extension of MDDT Encoding Polynucleotides  
     [0287] Full length polynucleotide sequences were also produced by extension of an appropriate fragment of the full length molecule using oligonucleotide primers designed from this fragment. One primer was synthesized to initiate 5′ extension of the known fragment, and the other primer was synthesized to initiate 3′ extension of the known fragment. The initial primers were designed using OLIGO 4.06 software (National Biosciences), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the target sequence at temperatures of about 68° C. to about 72° C. Any stretch of nucleotides which would result in hairpin structures and primer-primer dimerizations was avoided.  
     [0288] Selected human cDNA libraries were used to extend the sequence. If more than one extension was necessary or desired, additional or nested sets of primers were designed.  
     [0289] High fidelity amplification was obtained by PCR using methods well known in the art. PCR was performed in 96-well plates using the PTC-200 thermal cycler (MJ Research, Inc.). The reaction mix contained DNA template, 200 nmol of each primer, reaction buffer containing Mg 2+ , (NH 4 ) 2 SO 4 , and 2-mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase (Stratagene), with the following parameters for primer pair PCI A and PCI B: Step 1: 94° C., 3 min; Step 2: 94° C., 15 sec; Step 3: 60° C., 1 min; Step 4: 68° C., 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68° C., 5 min; Step 7: storage at 4° C. In the alternative, the parameters for primer pair T7 and SK+ were as follows: Step 1: 94° C., 3 min; Step 2: 94° C., 15 sec; Step 3: 57° C., 1 min; Step 4: 68° C., 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68° C., 5 min; Step 7: storage at 4° C.  
     [0290] The concentration of DNA in each well was determined by dispensing 100 μL PICOGREEN quantitation reagent (0.25% (v/v) PICOGREEN; Molecular Probes, Eugene Oreg.) dissolved in 1× TE and 0.5 μl of undiluted PCR product into each well of an opaque fluorimeter plate (Corning Costar, Acton Mass.), allowing the DNA to bind to the reagent. The plate was scanned in a Fluoroskan II (Labsystems Oy, Helsinki, Finland) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 μl to 10 μl aliquot of the reaction mixture was analyzed by electrophoresis on a 1% agarose gel to determine which reactions were successful in extending the sequence.  
     [0291] The extended nucleotides were desalted and concentrated, transferred to 384-well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison Wis.), and sonicated or sheared prior to religation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides were separated on low concentration (0.6 to 0.8%) agarose gels, fragments were excised, and agar digested with Agar ACE (Promega). Extended clones were religated using T4 ligase (New England Biolabs, Beverly Mass.) into pUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNA polymerase (Stratagene) to fill-in restriction site overhangs, and transfected into competent  E. coli  cells. Transformed cells were selected on antibiotic-containing media, and individual colonies were picked and cultured overnight at 37° C. in 384-well plates in LB/2× carb liquid media.  
     [0292] The cells were lysed, and DNA was amplified by PCR using Taq DNA polymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase (Stratagene) with the following parameters: Step 1: 94° C., 3 min; Step 2: 94° C., 15 sec; Step 3: 60° C., 1 min; Step 4: 72° C., 2 min; Step 5: steps 2, 3, and 4 repeated 29 times; Step 6: 72° C., 5 min; Step 7: storage at 4° C. DNA was quantified by PICOGREEN reagent (Molecular Probes) as described above. Samples with low DNA recoveries were reamplified using the same conditions as described above. Samples were diluted with 20% dimethysulfoxide (1:2, v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the DYENAMIC DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems).  
     [0293] In like manner, full length polynucleotide sequences are verified using the above procedure or are used to obtain 5′ regulatory sequences using the above procedure along with oligonucleotides designed for such extension, and an appropriate genomic library.  
     [0294] IX. Labeling and Use of Individual Hybridization Probes  
     [0295] Hybridization probes derived from SEQ ID NO:13-24 are employed to screen cDNAs, genomic DNAs, or mRNAs. Although the labeling of oligonucleotides, consisting of about 20 base pairs, is specifically described, essentially the same procedure is used with larger nucleotide fragments. Oligonucleotides are designed using state-of-the-art software such as OLIGO 4.06 software (National Biosciences) and labeled by combining 50 pmol of each oligomer, 250 μCi of [γ- 32 p] adenosine triphosphate (Amersham Pharmacia Biotech), and T4 polynucleotide kinase (DuPont NEN, Boston Mass.). The labeled oligonucleotides are substantially purified using a SEPHADEX G-25 superfine size exclusion dextran bead column (Amersham Pharmacia Biotech).  
     [0296] An aliquot containing 10 7  counts per minute of the labeled probe is used in a typical membrane-based hybridization analysis of human genomic DNA digested with one of the following endonucleases: Ase I, Bgl II, Eco RI, Pst I, Xba I, or Pvu II (DuPont NEN).  
     [0297] The DNA from each digest is fractionated on a 0.7% agarose gel and transferred to nylon membranes (Nytran Plus, Schleicher &amp; Schuell, Durham N.H.). Hybridization is carried out for 16 hours at 40° C. To remove nonspecific signals, blots are sequentially washed at room temperature under conditions of up to, for example, 0.1×saline sodium citrate and 0.5% sodium dodecyl sulfate. Hybridization patterns are visualized using autoradiography or an alternative imaging means and compared.  
     [0298] X. Microarrays  
     [0299] The linkage or synthesis of array elements upon a microarray can be achieved utilizing photolithography, piezoelectric printing (inkjet printing, See, e.g., Baldeschweiler, supra.), mechanical microspotting technologies, and derivatives thereof. The substrate in each of the aforementioned technologies should be uniform and solid with a non-porous surface (Schena (1999), supra). Suggested substrates include silicon, silica, glass slides, glass chips, and silicon wafers. Alternatively, a procedure analogous to a dot or slot blot may also be used to arrange and link elements to the surface of a substrate using thermal, UV, chemical, or mechanical bonding procedures. A typical array may be produced using available methods and machines well known to those of ordinary skill in the art and may contain any appropriate number of elements. (See, e.g., Schena, M. et al. (1995) Science 270:467470; Shalon, D. et al. (1996) Genome Res. 6:639-645; Marshall, A. and J. Hodgson (1998) Nat. Biotechnol. 16:27-31.)  
     [0300] Full length cDNAs, Expressed Sequence Tags (ESTs), or fragments or oligomers thereof may comprise the elements of the microarray. Fragments or oligomers suitable for hybridization can be selected using software well known in the art such as LASERGENE software (DNASTAR). The array elements are hybridized with polynucleotides in a biological sample. The polynucleotides in the biological sample are conjugated to a fluorescent label or other molecular tag for ease of detection. After hybridization, nonhybridized nucleotides from the biological sample are removed, and a fluorescence scanner is used to detect hybridization at each array element. Alternatively, laser desorbtion and mass spectrometry may be used for detection of hybridization. The degree of complementarity and the relative abundance of each polynucleotide which hybridizes to an element on the microarray may be assessed. In one embodiment, microarray preparation and usage is described in detail below.  
     [0301] Tissue or Cell Sample Preparation  
     [0302] Total RNA is isolated from tissue samples using the guanidinium thiocyanate method and poly(A) +  RNA is purified using the oligo-(dT) cellulose method. Each poly(A) +  RNA sample is reverse transcribed using MMLV reverse-transcriptase, 0.05 pg/μl oligo-(dT) primer (21 mer), 1× first strand buffer, 0.03 units/μl RNase inhibitor, 500 μM dATP, 500 μM dGTP, 500 μM dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng poly(A) +  RNA with GEMBRIGHT kits (Incyte). Specific control poly(A) +  RNAs are synthesized by in vitro transcription from non-coding yeast genomic DNA. After incubation at 37° C. for 2 hr, each reaction sample (one with Cy3 and another with Cy5 labeling) is treated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at 85° C. to the stop the reaction and degrade the RNA. Samples are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc. (CLONTECH), Palo Alto Calif.) and after combining, both reaction samples are ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodium acetate, and 300 ml of 100% ethanol. The sample is then dried to completion using a SpeedVAC (Savant Instruments Inc., Holbrook N.Y.) and resuspended in 14 μl 5× SSC/0.2% SDS.  
     [0303] Microarray Preparation  
     [0304] Sequences of the present invention are used to generate array elements. Each array element is amplified from bacterial cells containing vectors with cloned cDNA inserts. PCR amplification uses primers complementary to the vector sequences flanking the cDNA insert. Array elements are amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 μg. Amplified array elements are then purified using SEPHACRYL-400 (Amersham Pharmacia Biotech).  
     [0305] Purified array elements are immobilized on polymer-coated glass slides. Glass microscope slides (Coming) are cleaned by ultrasound in 0.1% SDS and acetone, with extensive distilled water washes between and after treatments. Glass slides are etched in 4% hydrofluoric acid (VWR Scientific Products Corporation (VWR), West Chester Pa.), washed extensively in distilled water, and coated with 0.05% aminopropyl silane (Sigma) in 95% ethanol. Coated slides are cured in a 110° C. oven.  
     [0306] Array elements are applied to the coated glass substrate using a procedure described in U.S. Pat. No. 5,807,522, incorporated herein by reference. 1 μl of the array element DNA, at an average concentration of 100 ng/μl, is loaded into the open capillary printing element by a high-speed robotic apparatus. The apparatus then deposits about 5 nl of array element sample per slide.  
     [0307] Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene). Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water. Non-specific binding sites are blocked by incubation of microarrays in 0.2% casein in phosphate buffered saline (PBS) (Tropix, Inc., Bedford Mass.) for 30 minutes at 60° C. followed by washes in 0.2% SDS and distilled water as before.  
     [0308] Hybridization  
     [0309] Hybridization reactions contain 9 μl of sample mixture consisting of 0.2 μg each of Cy3 and Cy5 labeled cDNA synthesis products in 5× SSC, 0.2% SDS hybridization buffer. The sample mixture is heated to 65° C. for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cm 2  coverslip. The arrays are transferred to a waterproof chamber having a cavity just slightly larger than a microscope slide. The chamber is kept at 100% humidity internally by the addition of 140 μl of 5× SSC in a corner of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60° C. The arrays are washed for 10 min at 45° C. in a first wash buffer (1× SSC, 0.1% SDS), three times for 10 minutes each at 45° C. in a second wash buffer (0.1× SSC), and dried.  
     [0310] Detection  
     [0311] Reporter-labeled hybridization complexes are detected with a microscope equipped with an Innova 70 mixed gas 10 W laser (Coherent, Inc., Santa Clara Calif.) capable of generating spectral lines at 488 nm for excitation of Cy3 and at 632 nm for excitation of Cy5. The excitation laser light is focused on the array using a 20× microscope objective (Nikon, Inc., Melville N.Y.). The slide containing the array is placed on a computer-controlled X-Y stage on the microscope and raster-scanned past the objective. The 1.8 cm×1.8 cm array used in the present example is scanned with a resolution of 20 micrometers.  
     [0312] In two separate scans, a mixed gas multiline laser excites the two fluorophores sequentially. Emitted light is split, based on wavelength, into two photomultiplier tube detectors (PMT R1477, Hamamatsu Photonics Systems, Bridgewater N.J.) corresponding to the two fluorophores. Appropriate filters positioned between the array and the photomultiplier tubes are used to filter the signals. The emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for Cy5. Each array is typically scanned twice, one scan per fluorophore using the appropriate filters at the laser source, although the apparatus is capable of recording the spectra from both fluorophores simultaneously.  
     [0313] The sensitivity of the scans is typically calibrated using the signal intensity generated by a cDNA control species added to the sample mixture at a known concentration. A specific location on the array contains a complementary DNA sequence, allowing the intensity of the signal at that location to be correlated with a weight ratio of hybridizing species of 1:100,000. When two samples from different sources (e.g., representing test and control cells), each labeled with a different fluorophore, are hybridized to a single array for the purpose of identifying genes that are differentially expressed, the calibration is done by labeling samples of the calibrating cDNA with the two fluorophores and adding identical amounts of each to the hybridization mixture.  
     [0314] The output of the photomultiplier tube is digitized using a 12-bit RTI-835H analog-to-digital (A/D) conversion board (Analog Devices, Inc., Norwood Mass.) installed in an IBM-compatible PC computer. The digitized data are displayed as an image where the signal intensity is mapped using a linear 20-color transformation to a pseudocolor scale ranging from blue (low signal) to red (high signal). The data is also analyzed quantitatively. Where two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping emission spectra) between the fluorophores using each fluorophore&#39;s emission spectrum.  
     [0315] A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte).  
     [0316] XI. Complementary Polynucleotides  
     [0317] Sequences complementary to the MDDT-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring MDDT. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentially the same procedure is used with smaller or with larger sequence fragments. Appropriate oligonucleotides are designed using OLIGO 4.06 software (National Biosciences) and the coding sequence of MDDT. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5′ sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to the MDDT-encoding transcript.  
     [0318] XII. Expression of MDDT  
     [0319] Expression and purification of MDDT is achieved using bacterial or virus-based expression systems. For expression of MDDT in bacteria, cDNA is subcloned into an appropriate vector containing an antibiotic resistance gene and an inducible promoter that directs high levels of cDNA transcription. Examples of such promoters include, but are not limited to, the trp-lac (tac) hybrid promoter and the T5 or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21(DE3). Antibiotic resistant bacteria express MDDT upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of MDDT in eukaryotic cells is achieved by infecting insect or mammalian cell lines with recombinant  Autographica californica  nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding MDDT by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infectivity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to infect  Spodoptera frugiperda  (Sf9) insect cells in most cases, or human hepatocytes, in some cases. Infection of the latter requires additional genetic modifications to baculovirus. (See Engelhard, E. K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945.)  
     [0320] In most expression systems, MDDT is synthesized as a fusion protein with, e.g., glutathione S-transferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26-kilodalton enzyme from  Schistosoma japonicum , enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). Following purification, the GST moiety can be proteolytically cleaved from MDDT at specifically engineered sites. FLAG, an 8-amino acid peptide, enables immunoaffinity purification using commercially available monoclonal and polyclonal anti-FLAG antibodies (Eastman Kodak). 6-His, a stretch of six consecutive histidine residues, enables purification on metal-chelate resins (QIAGEN). Methods for protein expression and purification are discussed in Ausubel (1995, supra, ch. 10 and 16). Purified MDDT obtained by these methods can be used directly in the assays shown in Example XVI, where applicable.  
     [0321] XIII. Functional Assays  
     [0322] MDDT function is assessed by expressing the sequences encoding MDDT at physiologically elevated levels in mammalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice include PCMV SPORT (Life Technologies) and PCR3.1 (Invitrogen, Carlsbad Calif.), both of which contain the cytomegalovirus promoter. 5-10 μg of recombinant vector are transiently transfected into a human cell line, for example, an endothelial or hematopoietic cell line, using either liposome formulations or electroporation. 1-2 μg of an additional plasmid containing sequences encoding a marker protein are co-transfected. Expression of a marker protein provides a means to distinguish transfected. cells from nontransfected cells and is a reliable predictor of cDNA expression from the recombinant vector. Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP; Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), an automated, laser optics-based technique, is used to identify transfected cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties. FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with cell death These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree side light scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular proteins as measured by reactivity with specific antibodies; and alterations in plasma membrane composition as measured by the binding of fluorescein-conjugated Annexin V protein to the cell surface. Methods in flow cytometry are discussed in Ormerod, M. G. (1994)  Flow Cytometry , Oxford, New York N.Y.  
     [0323] The influence of MDDT on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding MDDT and either CD64 or CD64-GFP. CD64 and CD64-GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Lake Success N.Y.). mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding MDDT and other genes of interest can be analyzed by northern analysis or microarray techniques.  
     [0324] XIV. Production of MDDT Specific Antibodies  
     [0325] MDDT substantially purified using polyacrylamide gel electrophoresis (PAGE; see, e.g., Harrington, M. G. (1990) Methods Enzymol. 182:488495), or other purification techniques, is used to immunize rabbits and to produce antibodies using standard protocols.  
     [0326] Alternatively, the MDDT amino acid sequence is analyzed using LASERGENE software (DNASTAR) to determine regions of high immunogenicity, and a corresponding oligopeptide is synthesized and used to raise antibodies by means known to those of skill in the art. Methods for selection of appropriate epitopes, such as those near the C-terminus or in hydrophilic regions are well described in the art. (See, e.g., Ausubel, 1995, supra, ch. 11.)  
     [0327] Typically, oligopeptides of about 15 residues in length are synthesized using an ABI 431A peptide synthesizer (Applied Biosystems) using FMOC chemistry and coupled to KLH (Sigma-Aldrich, St. Louis Mo.) by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase immunogenicity. (See, e.g., Ausubel, 1995, supra.) Rabbits are immunized with the oligopeptide-KLH complex in complete Freund&#39;s adjuvant. Resulting antisera are tested for antipeptide and anti-MDDT activity by, for example, binding the peptide or MDDT to a substrate, blocking with 1% BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.  
     [0328] XV. Purification of Naturally Occurring MDDT Using Specific Antibodies  
     [0329] Naturally occurring or recombinant MDDT is substantially purified by immunoaffinity chromatography using antibodies specific for MDDT. An immunoaffinity column is constructed by covalently coupling anti-MDDT antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer&#39;s instructions.  
     [0330] Media containing MDDT are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of MDDT (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/MDDT binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and MDDT is collected.  
     [0331] XVI. Demonstration of MDDT Activity  
     [0332] MDDT, or biologically active fragments thereof, are labeled with  125 I Bolton-Hunter reagent. (See, e.g., Bolton, A. E. and W. M. Hunter (1973) Biochem. J. 133:529-539.) Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled MDDT, washed, and any wells with labeled MDDT complex are assayed. Data obtained using different concentrations of MDDT are used to calculate values for the number, affinity, and association of MDDT with the candidate molecules.  
     [0333] Alternatively, molecules interacting with MDDT are analyzed using the yeast two-hybrid system as described in Fields, S. and O. Song (1989) Nature 340:245-246, or using commercially available kits based on the two-hybrid system, such as the MATCHMAKER system (Clontech).  
     [0334] MDDT may also be used in the PATHCALLING process (CuraGen Corp., New Haven Conn.) which employs the yeast two-hybrid system in a high-throughput manner to determine all interactions between the proteins encoded by two large libraries of genes (Nandabalan, K. et al. (2000) U.S. Pat. No. 6,057,101).  
     [0335] Various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in molecular biology or related fields are intended to be within the scope of the following claims.  
                               TABLE 1                               Incyte   Poly-           Incyte   Polypeptide   Polypeptide   nucleotide   Incyte       Project ID   SEQ ID NO:   ID   SEQ ID NO:   Polynucleotide ID                                                    2344051   1   2344051CD1   13   2344051CB1       2257655   2   2257655CD1   14   2257655CB1       1520554   3   1520554CD1   15   1520554CB1       1965924   4   1965924CD1   16   1965924CB1       2073295   5   2073295CD1   17   2073295CB1       3054202   6   3054202CD1   18   3054202CB1       5316792   7   5316792CD1   19   5316792CB1       5572967   8   5572967CD1   20   5572967CB1       7473247   9   7473247CD1   21   7473247CB1       7482930   10   7482930CD1   22   7482930CB1       2049942   11   2049942CD1   23   2049942CB1       2418711   12   2418711CD1   24   2418711CB1                  
 
     [0336]                               TABLE 2                           Incyte                   Polypeptide   Polypeptide   GenBank   Probability   GenBank       SEQ ID NO:   ID   ID NO:   Score   Homolog                                                    1   2344051CD1   g8176525   3.7E−155   Interferon-inducible myeloid differentiation                       transcriptional activator [ Homo sapiens ]                       (Johnstone, R. W. et al. (1998) J. Biol. Chem.                       273: 17172-17177)       11   2049942CD1   g7677357   1.1E−171   EDAG-1 [ Homo sapiens ]       12   2418711CD1   g1334880   1.3E−22   BKRF1 encodes EBNA-1 protein, latent cycle gene [Human                       herpesvirus 4]                    
     [0337]                                       TABLE 3                       SEQ   Incyte   Amino   Potential   Potential       Analytical       ID   Polypeptide   Acid   Phosphorylation   Glycosylation   Signature Sequences,   Methods and       NO:   ID   Residues   Sites   Sites   Domains and Motifs   Databases                                                            1   2344051CD1   461   S104 S122   N188 N221   NUCLEAR; DIFFERENTIATION; MYELOID;   BLAST-DOMO                   S143 S190   N273 N384   ANTIGEN;                   S194 S231       DM02433|P41218|166-397: T169-K400                   S275 S279       DM02433|P15092|205-416: T171-R380                   S288 T126       DM02433|P15091|15-223: G174-R380                   T149 T342       DM05299|P41218|1-164: M1-S168                   T430 T74 T81       PROTEIN NUCLEAR REPEAT   BLAST-                           INTERFERONINDUCIBLE MYELOID   PRODOM                           DIFFERENTIATION ACTIVATOR                           PD134308: T126-F395                           PD007764: Q137-K400                           PD014209: Y5-V89                           PD134282: N403-D457       2   2257655CD1   329   S199 S290   N183   Eukaryotic thiol (cysteine) proteases   MOTIFS                   S296 S56 S7       histidine active site: S227-A237                   S9 T115 T265                   T34 T86       3   1520554CD1   683   S262 S272   N201 N243                   S446 S496   N303 N350                   S508 S535   N412 N588                   S540 S82   N652                   T214 T235                   T245 T352                   T413 T414                   T447 T489                   T622 T75       4   1965924CD1   1150   S1044 S1075   N1076   SAP DNA binding domain: P636-L670   HMMER-PFAM                   S302 S329   N1112   TYPE I ANTIFREEZE PROTEIN   BLIMPS-                   S339 S343   N1117 N212   PR00308: T46-T57, Q72-Q81   PRINTS                   S351 S446       TRICHOHYALIN   BLAST-DOMO                   S456 S584       DM03839|P37709|632-1103: D643-Q1092                   S632 S654       do EUKARYOTIC; RNA; RNP-1;   BLAST-DOMO                   S685 S697       DM07068|P09406|303-470: E795-P907                   S739 S792       Tropomyosins signature   BLAST-DOMO                   S806 S832       DM00077|P53935|580-755: E795-R897                   S855 S983       SIMILAR TO AXONEMEASSOCIATED   BLAST-                   S994 T1010       PROTEIN MST101 PD185497: L444-E863   PRODOM                   T1062 T1114       PROTEIN REPEAT TROPOMYOSIN COILED   BLAST-                   T1120 T134       COIL ALTERNATIVE SPLICING SIGNAL   PRODOM                   T400 T532       PRECURSOR CHAIN PD000023: K788-Q917                   T556 T582       PROTEIN COILED COIL CHAIN MYOSIN   BLAST-                   T638 T861       REPEAT HEAVY ATPBINDING FILAMENT   PRODOM                   T891 T980       HEPTAD PD000002: L597-R845                   T982 Y192                   Y550 Y721                   Y950       5   2073295CD1   349   S196 S210   N106 N300                   S258 T243   N56                   T263 T6 T61       6   3054202CD1   510   S120 S132   N303 N88   IP63 INSULINOMA PROTEIN   BLAST-                   S171 S176       PD144937: M1-A412   PRODOM                   S20 S236                   S238 S249                   S290 S305                   S442 S486                   S499 S501                   S56 T139                   T146 T158                   T16 T165                   T257 T38                   T505 T9       7   5316792CD1   91       8   5572967CD1   599   S156 S18   N243                   S181 S213                   S332 S359                   S389 S401                   S44 S591 S61                   T115 T245                   T31 T313                   T369 T90 T92                   T98       9   7473247CD1   128   S122 S20 S6                   S83 S90 T108                   T12 T126 T97       10   7482930CD1   859   S114 S157   N154 N325                   S192 S194   N364 N681                   S207 S269   N732                   S321 S341                   S363 S401                   S470 S494                   S536 S569                   S578 S612                   S614 S650                   S663 S716                   S718 S734                   S769 S814                   S815 S843                   T17 T228                   T249 T332                   T46 T525                   T544 T71 T78                   T84       11   2049942CD1   484   S167 S173   N146 N157                   S187 S311   N186 N285                   S33 S339   N470                   S363 S389                   S472 T246                   T314 T328                   T342 T370                   T412 T68       12   2418711CD1   631   S209 S235   N205 N56   PHASEOLUS GLYCINE-RICH CELL WALL   BLAST-DOMO                   S240 S271       PROTEIN 1.8                   S433 S76 S85       DM07973|P09789|1-383: G327-G444                   T116 T194       DM07973|P27483|1-337: G327-G444                   T373 T62                   Y202                    
     [0338]                                       TABLE 4                           Incyte                           Polynucleotide   Polynucleotide   Sequence   Selected   Sequence   5′   3′       SEQ ID NO:   ID   Length   Fragments   Fragments   Position   Position                                                            13   2344051CB1   1892   953-1236,   146222R6 (TLYMNOR01)   1492   1892                   1685-1743,   4630228H1 (GBLADIT02)   1161   1419                   453-500   4906137F6 (TLYMNOT08)   513   1040                       2344051F6 (TESTTUT02)   1230   1707                       5427025F8 (THYMTUT03)   573   1243                       3043683F6 (HEAANOT01)   1   538       14   2257655CB1   2693   1-287,   7364155H1 (OVARDIC01)   847   1358                   2146-2693,   2257655H1 (OVARTUT01)   2559   2693                   1-748,   70788230V1   1   588                   1890-2129   7126189H1 (COLNDIY01)   1520   2119                       3031273T6 (TLYMNOT05)   2059   2687                       7614138H1 (COLNTUN03)   1314   1889                       6045546H1 (BRABDIR02)   451   1064       15   1520554CB1   2351   1-455,   6197448H1 (PITUNON01)   395   1032                   1-315,   7171609H1 (BRSTTMC01)   1   478                   677-744   70929134V1   609   1201                       71278047V1   1716   2246                       7368901H1 (ADREFEC01)   965   1591                       7344022H1 (SYNODIN02)   1807   2351                       6749651H1 (BRAXNOT03)   1192   1732       16   1965924CB1   3827   3373-3827,   1823413T6 (GBLATUT01)   2583   3249                   2473-2676,   1720515F6 (BLADNOT06)   1357   1760                   1041-1375,   1823413F6 (GBLATUT01)   1633   2222                   816-939,   1486201F6 (CORPNOT02)   377   900                   1451-1609,   223613R1 (PANCNOT01)   2710   3469                   1707-1904,   1309122R1 (COLNFET02)   3532   3827                   2627-2877,   2725227F6 (OVARTUT05)   1226   1680                   3356-3827   SBYA05418U1   733   1247                       775882T1 (COLNNOT05)   3097   3819                       3465177H1 (293TF2T01)   2356   2604                       4288353H1 (LIVRDIR01)   2419   2619                       783001R7 (MYOMNOT01)   1840   2418                       2593582F6 (OVARTUT02)   1   483       17   2073295CB1   2193   1502-1551,   70571754V1   1211   1783                   1-139,   72330149V1   597   1318                   1964-2193,   70568561V1   1485   2193                   1973-2193,   2073295T6 (ISLTNOT01)   1395   1945                   1-221,   71816394V1   466   1218                   1501-1602   2457736F6 (ENDANOT01)   1   568       18   3054202CB1   2926   1-369,   2815081T6 (OVARNOT10)   2311   2926                   2737-2926,   1309370F6 (COLNFET02)   1044   1618                   1588-1633,   8185929H1 (EYERNON01)   474   1106                   2032-2184,   7986390H2 (UTRSTUC01)   1851   2383                   1-538,   70764014V1   809   1134                   1008-1062,   70688692V1   1748   2368                   1591-1629,   7586963H1 (BRAIFEC01)   1   591                   1856-2203   70769154V1   1198   1766       19   5316792CB1   279       5024015H1 (OVARNON03)   1   206                       GBI.g9954663_000016.edit   1   279       20   5572967CB1   2131   386-449,   g2205989   1729   2131                   800-1250   3970066F6 (PROSTUT10)   469   980                       1957687H1 (CONNNOT01)   1608   1875                       70718811V1   1766   2131                       70715733V1   469   1064                       70719927V1   1358   1934                       70681384V1   1059   1658                       2228991F6 (PROSNOT16)   688   1212                       6913186J1 (PITUDIR01)   1   517       21   7473247CB1   880   1-86   6854652F6 (BRAIFEN08)   2   796                       2839513H2 (DRGLNOT01)   1   261                       6883792H1 (BRAHTDR03)   409   880       22   7482930CB1   3787   693-1012,   71276004V1   1205   1672                   3592-3787,   g4240182   1080   3097                   1756-2374,   70522941V1   3053   3787                   1-380,   71622781V1   2922   3533                   693-1303,   70923806V1   704   1319                   1697-1891,   71623728V1   2373   3056                   2561-2753,   2268395H1 (UTRSNOT02)   1570   1821                   3264-3787   5841547H2 (BRAENOT04)   1900   2172                       7160675F8 (HNT2TXC01)   1   780                       71274775V1   771   1326       23   2049942CB1   2130   1735-1763,   70813868V1   724   1113                   2049-2130,   1671256F6 (BMARNOT03)   1   586                   1-436   2049942F6 (LIVRFET02)   1347   1734                       70812387V1   505   1111                       2205880F6 (SPLNFET02)   960   1321                       1671256T6 (BMARNOT03)   1465   2130                       026527H1 (SPLNFET01)   1221   1392       24   2418711CB1   2607   1452-1972,   71874646V1   393   896                   68-167,   GBI.g7139848.edit   1   341                   1086-1145,   GBI.g7139848.edit.3   1695   2607                   403-1583,   g3934182   1968   2417                   1663-1827   3332927H1 (BRAIFET01)   173   270                       7359887H1 (BRAIFEE05)   947   1464                       71873017V1   249   766                       72335680V1   734   1046                       7589468H2 (BRAIFEC01)   1270   1822                       g4617984   1564   1975                    
     [0339]                       TABLE 5                       Polynucleotide   Incyte   Representative       SEQ ID NO:   Project ID   Library                                            13   2344051CB1   TLYMNOT08       14   2257655CB1   TLYMNOT05       15   1520554CB1   BRAENOT02       16   1965924CB1   CORPNOT02       17   2073295CB1   ISLTNOT01       18   3054202CB1   LUNGNON03       19   5316792CB1   OVARNON03       20   5572967CB1   THP1PLB02       21   7473247CB1   BRAIFEN08       22   7482930CB1   NOSEDIT01       23   2049942CB1   BMARNOR02       24   2418711CB1   BRAITUT03                    
     [0340]                       TABLE 6                       Library   Vector   Library Description                  BMARNOR02   PBLUESCRIPT   Library was constructed using RNA isolated from the bone marrow of 24 male and               female Caucasian donors, 16 to 70 years old. (RNA came from Clontech.)       BRAENOT02   pINCY   Library was constructed using RNA isolated from posterior parietal cortex tissue               removed from the brain of a 35-year-old Caucasian male who died from cardiac               failure.       BRAIFEN08   pINCY   This normalized fetal brain tissue library was constructed from 400 thousand               independent clones from a fetal brain tissue library. Starting RNA was made from               brain tissue removed from a Caucasian male fetus who was stillborn with a               hypoplastic left heart at 23 weeks&#39; gestation. The library was normalized in 2               rounds using conditions adapted from Soares et al., PNAS (1994) 91: 9228 and               Bonaldo et al., Genome Research (1996) 6: 791, except that a significantly longer               (48 hours/round) reannealing hybridization was used.       BRAITUT03   PSPORT1   Library was constructed using RNA isolated from brain tumor tissue removed from               the left frontal lobe of a 17-year-old Caucasian female during excision of a               cerebral meningeal lesion. Pathology indicated a grade 4 fibrillary giant and               small-cell astrocytoma. Family history included benign hypertension and               cerebrovascular disease.       CORPNOT02   pINCY   Library was constructed using RNA isolated from diseased corpus callosum tissue               removed from the brain of a 74-year-old Caucasian male who died from Alzheimer&#39;s               disease.       ISLTNOT01   pINCY   Library was constructed using RNA isolated from a pooled collection of pancreatic               islet cells.       LUNGNON03   PSPORT1   This normalized library was constructed from 2.56 million independent clones from               a lung tissue library. RNA was made from lung tissue removed from the left lobe a               58-year-old Caucasian male during a segmental lung resection. Pathology for the               associated tumor tissue indicated a metastatic grade 3 (of 4) osteosarcoma.               Patient history included soft tissue cancer, secondary cancer of the lung,               prostate cancer, and an acute duodenal ulcer with hemorrhage. Patient also               received radiation therapy to the retroperitoneum. Family history included               prostate cancer, breast cancer, and acute leukemia. The normalization and               hybridization conditions were adapted from Soares et al., PNAS (1994) 91: 9228;               Swaroop et al., NAR (1991) 19: 1954; and Bonaldo et al., Genome Research (1996)               6: 791.       NOSEDIT01   pINCY   Library was constructed using RNA isolated from nasal polyp tissue.       OVARNON03   pINCY   This normalized ovarian tissue library was constructed from 5 million independent               clones from an ovary library. Starting RNA was made from ovarian tissue removed               from a 36-year-old Caucasian female during total abdominal hysterectomy, bilateral               salpingo-oophorectomy, soft tissue excision, and an incidental appendectomy.               Pathology for the associated tumor tissue indicated one intramural and one               subserosal leiomyomata of the myometrium. The endometrium was proliferative phase.               Patient history included deficiency anemia, calculus of the kidney, and a kidney               anomaly. Family history included hyperlipidemia, acute myocardial infarction,               atherosclerotic coronary artery disease, type II diabetes,and chronic liver               disease. The library was normalized in two rounds using conditions adapted from               Soares et al., PNAS (1994) 91: 9228 and Bonaldo et al., Genome Research (1996)               6: 791, except that a significantly longer (48 hours/round) reannealing               hybridization was used.       THP1PLB02   PBLUESCRIPT   Library was constructed using RNA isolated from THP-1 cells cultured for 48 hours               with 100 ng/ml phorbol ester (PMA), followed by a 4-hour culture in media               containing 1 ug/ml LPS. THP-1 is a human promonocyte line derived from the               peripheral blood of a 1-year-old male with acute monocytic leukemia.       TLYMNOT05   pINCY   Library was constructed using RNA isolated from nonactivated Th2 cells. These               cells were differentiated from umbilical cord CD4 T cells with IL-4 in the               presence of anti-IL-12 antibodies and B7-transfected COS cells.       TLYMNOT08   pINCY   Library was constructed using RNA isolated from anergic allogenic T-lymphocyte               tissue removed from an adult (40-50-year-old) Caucasian male. The cells were               incubated for 3 days in the presence of 1 microgram/ml OKT3 mAb and 5% human               serum.                    
     [0341]                           TABLE 7                       Program   Description   Reference   Parameter Threshold                  ABI   A program that removes vector sequences and   Applied Biosystems, Foster City, CA.           FACTURA   masks ambiguous bases in nucleic acid sequences.       ABI/   A Fast Data Finder useful in comparing and   Applied Biosystems, Foster City, CA;   Mismatch &lt; 50%       PARACEL   annotating amino acid or nucleic acid sequences.   Paracel Inc., Pasadena, CA.       FDF       ABI Auto-   A program that assembles nucleic acid sequences.   Applied Biosystems, Foster City, CA.       Assembler       BLAST   A Basic Local Alignment Search Tool useful in   Altschul, S. F. et al. (1990) J. Mol. Biol.   ESTs: Probability value = 1.0E−8           sequence similarity search for amino acid and   215: 403-410; Altschul, S. F. et al. (1997)   or less           nucleic acid sequences. BLAST includes five   Nucleic Acids Res. 25: 3389-3402.   Full Length sequences: Probability           functions: blastp, blastn, blastx, tblastn, and tblastx.       value = 1.0E−10 or less       FASTA   A Pearson and Lipman algorithm that searches for   Pearson, W. R. and D. J. Lipman (1988) Proc.   ESTs: fasta E value = 1.06E−6           similarity between a query sequence and a group of   Natl. Acad Sci. USA 85: 2444-2448; Pearson,   Assembled ESTs: fasta Identity =           sequences of the same type. FASTA comprises as   W. R. (1990) Methods Enzymol. 183: 63-98;   95% or greater and           least five functions: fasta, tfasta, fastx, tfastx, and   and Smith, T. F. and M. S. Waterman (1981)   Match length = 200 bases or great-           ssearch.   Adv. Appl. Math. 2: 482-489.   er; fastx E value = 1.0E−8 or less                   Full Length sequences:                   fastx score = 100 or greater       BLIMPS   A BLocks IMProved Searcher that matches a   Henikoff, S. and J. G. Henikoff (1991) Nucleic   Probability value = 1.0E−3 or less           sequence against those in BLOCKS, PRINTS,   Acids Res. 19: 6565-6572; Henikoff, J. G. and           DOMO, PRODOM, and PFAM databases to search   S. Henikoff (1996) Methods Enzymol.           for gene families, sequence homology, and   266: 88-105; and Attwood, T. K. et al.           structural fingerprint regions.   (1997) J. Chem. Inf. Comput. Sci. 37:               417-424.       HMMER   An algorithm for searching a query sequence against   Krogh, A. et al. (1994) J. Mol. Biol.   PFAM hits: Probability value =           hidden Markov model (HMM)-based databases of   235: 1501-1531; Sonnhammer, E. L. L. et al.   1.0E−3 or less           protein family consensus sequences, such as PFAM.   (1988) Nucleic Acids Res. 26: 320-322;   Signal peptide hits: Score = 0 or               Durbin, R. et al. (1998) Our World View, in a   greater               Nutshell, Cambridge Univ. Press, pp. 1-350.       ProfileScan   An algorithm that searches for structural and   Gribskov, M. et al. (1988) CABIOS 4: 61-66;   Normalized quality score ≧ GCG-           sequence motifs in protein sequences that match   Gribskov, M. et al. (1989) Methods Enzymol.   specified “HIGH” value for that           defined in Prosite.   183: 146-159; Bairoch, A. et al. (1997)   particular Prosite motif.               Nucleic Acids Res. 25: 217-221.   Generally, score = 1.4-2.1.       Phred   A base-calling algorithm that examines automated   Ewing, B. et al. (1998) Genome Res.           sequencer traces with high sensitivity and   8: 175-185; Ewing, B. and P. Green           probability.   (1998) Genome Res. 8: 186-194.       Phrap   A Phils Revised Assembly Program including   Smith, T. F. and M. S. Waterman (1981) Adv.   Score = 120 or greater;           SWAT and CrossMatch, programs based on   Appl. Math. 2: 482-489; Smith, T. F. and   Match length = 56 or greater           efficient implementationof the Smith-Waterman   M. S. Waterman (1981) J. Mol. Biol. 147:           algorithm, useful in searching sequence homology   195-197; and Green, P., University of           and assembling DNA sequences.   Washington, Seattle, WA.       Consed   A graphical tool for viewing and editing Phrap   Gordon, D. et al. (1998) Genome Res.           assemblies.   8: 195-202.       SPScan   A weight matrix analysis program that scans protein   Nielson, H. et al. (1997) Protein Engineering   Score = 3.5 or greater           sequences for the presence of secretory   10: 1-6; Claverie, J. M. and S. Audic (1997)           signal peptides.   CABIOS 12: 431-439.       TMAP   A program that uses weight matrices to delineate   Persson, B. and P. Argos (1994) J. Mol. Biol.           transmembrane segments on protein sequences and   237: 182-192; Persson, B. and P. Argos (1996)           determine orientation.   Protein Sci. 5: 363-371.       TMHMMER   A program that uses a hidden Markov   Sonnhammer, E. L. et al. (1998) Proc. Sixth           model (HMM) to delineate transmembrane segments   Intl. Conf. on Intelligent Systems for Mol.           on protein sequences and determine orientation.   Biol., Glasgow et al., eds., The Am.               Assoc. for Artificial Intelligence Press,               Menlo Park, CA, pp. 175-182.       Motifs   A program that searches amino acid sequences for   Bairoch, A. et al. (1997) Nucleic Acids Res.           patterns that matched those defined in Prosite.   25: 217-221; Wisconsin Package Program               Manual, version 9, page M51-59, Genetics               Computer Group, Madison, WI.                    
     [0342] 
    
     
       
         1 
         
           
             24  
           
           
             1  
             461  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2344051CD1  
             
           
            1 

Met Ala Asn Asn Tyr Lys Lys Ile Val Leu Leu Lys Gly Leu Glu 
  1               5                  10                  15 

Val Ile Asn Asp Tyr His Phe Arg Ile Val Lys Ser Leu Leu Ser 
                 20                  25                  30 

Asn Asp Leu Lys Leu Asn Pro Lys Met Lys Glu Glu Tyr Asp Lys 
                 35                  40                  45 

Ile Gln Ile Ala Asp Leu Met Glu Glu Lys Phe Pro Gly Asp Ala 
                 50                  55                  60 

Gly Leu Gly Lys Leu Ile Glu Phe Phe Lys Glu Ile Pro Thr Leu 
                 65                  70                  75 

Gly Asp Leu Ala Glu Thr Leu Lys Arg Glu Lys Leu Lys Val Ala 
                 80                  85                  90 

Asn Lys Ile Glu Ser Ile Pro Val Lys Gly Ile Ile Pro Ser Lys 
                 95                 100                 105 

Lys Thr Lys Gln Lys Glu Val Tyr Pro Ala Thr Pro Ala Cys Thr 
                110                 115                 120 

Pro Ser Asn Arg Leu Thr Ala Lys Gly Ala Glu Glu Thr Leu Gly 
                125                 130                 135 

Pro Gln Lys Arg Lys Lys Pro Ser Glu Glu Glu Thr Gly Thr Lys 
                140                 145                 150 

Arg Ser Lys Met Ser Lys Glu Gln Thr Arg Pro Ser Cys Ser Ala 
                155                 160                 165 

Gly Ala Ser Thr Ser Thr Ala Met Gly Arg Ser Pro Pro Pro Gln 
                170                 175                 180 

Thr Ser Ser Ser Ala Pro Pro Asn Thr Ser Ser Thr Glu Ser Leu 
                185                 190                 195 

Lys Pro Leu Ala Asn Arg His Ala Thr Ala Ser Lys Asn Ile Phe 
                200                 205                 210 

Arg Glu Asp Pro Ile Ile Ala Met Val Leu Asn Ala Thr Lys Val 
                215                 220                 225 

Phe Lys Tyr Glu Ser Ser Glu Asn Glu Gln Arg Arg Met Phe His 
                230                 235                 240 

Ala Thr Val Ala Thr Gln Thr Gln Phe Phe His Val Lys Val Leu 
                245                 250                 255 

Asn Ile Asn Leu Lys Arg Lys Phe Ile Lys Lys Arg Ile Ile Ile 
                260                 265                 270 

Ile Ser Asn Tyr Ser Lys Arg Asn Ser Leu Leu Glu Val Asn Glu 
                275                 280                 285 

Ala Ser Ser Val Ser Glu Ala Gly Pro Asp Gln Thr Phe Glu Val 
                290                 295                 300 

Pro Lys Asp Ile Ile Arg Arg Ala Lys Lys Ile Pro Lys Ile Asn 
                305                 310                 315 

Ile Leu His Lys Gln Thr Ser Gly Tyr Ile Val Tyr Gly Leu Phe 
                320                 325                 330 

Met Leu His Thr Lys Ile Val Asn Arg Lys Thr Thr Ile Tyr Glu 
                335                 340                 345 

Ile Gln Asp Lys Thr Gly Ser Met Ala Val Val Gly Lys Gly Glu 
                350                 355                 360 

Cys His Asn Ile Pro Cys Glu Lys Gly Asp Lys Leu Arg Leu Phe 
                365                 370                 375 

Cys Phe Arg Leu Arg Lys Arg Glu Asn Met Ser Lys Leu Met Ser 
                380                 385                 390 

Glu Met His Ser Phe Ile Gln Ile Gln Lys Asn Thr Asn Gln Arg 
                395                 400                 405 

Ser His Asp Ser Arg Ser Met Ala Leu Pro Gln Glu Gln Ser Gln 
                410                 415                 420 

His Pro Lys Pro Ser Glu Ala Ser Thr Thr Leu Pro Glu Ser His 
                425                 430                 435 

Leu Lys Thr Pro Gln Met Pro Pro Thr Thr Pro Ser Ser Ser Ser 
                440                 445                 450 

Phe Thr Lys Val Thr Lys Asp Lys Asp Ile Lys 
                455                 460 

 
           
             2  
             329  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2257655CD1  
             
           
            2 

Met Glu Met Ser Gly Leu Ser Phe Ser Glu Met Glu Gly Cys Arg 
  1               5                  10                  15 

Asn Leu Leu Gly Leu Leu Asp Asn Asp Glu Ile Met Ala Leu Cys 
                 20                  25                  30 

Asp Thr Val Thr Asn Arg Leu Val Gln Pro Gln Asp Arg Gln Asp 
                 35                  40                  45 

Ala Val His Ala Ile Leu Ala Tyr Ser Gln Ser Ala Glu Glu Leu 
                 50                  55                  60 

Leu Arg Arg Arg Lys Val His Arg Glu Val Ile Phe Lys Tyr Leu 
                 65                  70                  75 

Ala Thr Gln Gly Ile Val Ile Pro Pro Ala Thr Glu Lys His Asn 
                 80                  85                  90 

Leu Ile Gln His Ala Lys Asp Tyr Trp Gln Lys Gln Pro Gln Leu 
                 95                 100                 105 

Lys Leu Lys Glu Thr Pro Glu Pro Val Thr Lys Thr Glu Asp Ile 
                110                 115                 120 

His Leu Phe Gln Gln Gln Val Lys Glu Asp Lys Lys Ala Glu Lys 
                125                 130                 135 

Val Asp Phe Arg Arg Leu Gly Glu Glu Phe Cys His Trp Phe Phe 
                140                 145                 150 

Gly Leu Leu Asn Ser Gln Asn Pro Phe Leu Gly Pro Pro Gln Asp 
                155                 160                 165 

Glu Trp Gly Pro Gln His Phe Trp His Asp Val Lys Leu Arg Phe 
                170                 175                 180 

Tyr Tyr Asn Thr Ser Glu Gln Asn Val Met Asp Tyr His Gly Ala 
                185                 190                 195 

Glu Ile Val Ser Leu Arg Leu Leu Ser Leu Val Lys Glu Glu Phe 
                200                 205                 210 

Leu Phe Leu Ser Pro Asn Leu Asp Ser His Gly Leu Lys Cys Ala 
                215                 220                 225 

Ser Ser Pro His Gly Leu Val Met Val Gly Val Ala Gly Thr Val 
                230                 235                 240 

His Arg Gly Asn Thr Cys Leu Gly Ile Phe Glu Gln Ile Phe Gly 
                245                 250                 255 

Leu Ile Arg Cys Pro Phe Val Glu Asn Thr Trp Lys Ile Lys Phe 
                260                 265                 270 

Ile Asn Leu Lys Ile Met Gly Glu Ser Ser Leu Ala Pro Gly Thr 
                275                 280                 285 

Leu Pro Lys Pro Ser Val Lys Phe Glu Gln Ser Asp Leu Glu Ala 
                290                 295                 300 

Phe Tyr Asn Val Ile Thr Val Cys Gly Thr Asn Glu Val Arg His 
                305                 310                 315 

Asn Val Lys Gln Ala Ser Asp Ser Gly Thr Gly Asp Gln Val 
                320                 325 

 
           
             3  
             683  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1520554CD1  
             
           
            3 

Met Lys Ser His Leu Met Val Gln Met Gly Glu Glu Tyr Tyr Tyr 
  1               5                  10                  15 

Ala Lys Asp Tyr Thr Lys Ala Leu Lys Leu Leu Asp Tyr Val Met 
                 20                  25                  30 

Cys Asp Tyr Arg Ser Glu Gly Trp Trp Thr Leu Leu Thr Ser Val 
                 35                  40                  45 

Leu Thr Thr Ala Leu Lys Cys Ser Tyr Leu Met Ala Gln Leu Lys 
                 50                  55                  60 

Asp Tyr Ile Thr Tyr Ser Leu Glu Leu Leu Gly Arg Ala Ser Thr 
                 65                  70                  75 

Leu Lys Asp Asp Gln Lys Ser Arg Ile Glu Lys Asn Leu Ile Asn 
                 80                  85                  90 

Val Leu Met Asn Glu Ser Pro Asp Pro Glu Pro Asp Cys Asp Ile 
                 95                 100                 105 

Leu Ala Val Lys Thr Ala Gln Lys Leu Trp Ala Asp Arg Ile Ser 
                110                 115                 120 

Leu Ala Gly Ser Asn Ile Phe Thr Ile Gly Val Gln Asp Phe Val 
                125                 130                 135 

Pro Phe Val Gln Cys Lys Ala Lys Phe His Ala Pro Ser Phe His 
                140                 145                 150 

Val Asp Val Pro Val Gln Phe Asp Ile Tyr Leu Lys Ala Asp Cys 
                155                 160                 165 

Pro His Pro Ile Arg Phe Ser Lys Leu Cys Val Ser Phe Asn Asn 
                170                 175                 180 

Gln Glu Tyr Asn Gln Phe Cys Val Ile Glu Glu Ala Ser Lys Ala 
                185                 190                 195 

Asn Glu Val Leu Glu Asn Leu Thr Gln Gly Lys Met Cys Leu Val 
                200                 205                 210 

Pro Gly Lys Thr Arg Lys Leu Leu Phe Lys Phe Val Ala Lys Thr 
                215                 220                 225 

Glu Asp Val Gly Lys Lys Ile Glu Ile Thr Ser Val Asp Leu Ala 
                230                 235                 240 

Leu Gly Asn Glu Thr Gly Arg Cys Val Val Leu Asn Trp Gln Gly 
                245                 250                 255 

Gly Gly Gly Asp Ala Ala Ser Ser Gln Glu Ala Leu Gln Ala Ala 
                260                 265                 270 

Arg Ser Phe Lys Arg Arg Pro Lys Leu Pro Asp Asn Glu Val His 
                275                 280                 285 

Trp Asp Ser Ile Ile Ile Gln Ala Ser Thr Met Ile Ile Ser Arg 
                290                 295                 300 

Val Pro Asn Ile Ser Val His Leu Leu His Glu Pro Pro Ala Leu 
                305                 310                 315 

Thr Asn Glu Met Tyr Cys Leu Val Val Thr Val Gln Ser His Glu 
                320                 325                 330 

Lys Thr Gln Ile Arg Asp Val Lys Leu Thr Ala Gly Leu Lys Pro 
                335                 340                 345 

Gly Gln Asp Ala Asn Leu Thr Gln Lys Thr His Val Thr Leu His 
                350                 355                 360 

Gly Thr Glu Leu Cys Asp Glu Ser Tyr Pro Ala Leu Leu Thr Asp 
                365                 370                 375 

Ile Pro Val Gly Asp Leu His Pro Gly Glu Gln Leu Glu Lys Met 
                380                 385                 390 

Leu Tyr Val Arg Cys Gly Thr Val Gly Ser Arg Met Phe Leu Val 
                395                 400                 405 

Tyr Val Ser Tyr Leu Ile Asn Thr Thr Val Glu Glu Lys Glu Ile 
                410                 415                 420 

Val Cys Lys Cys His Lys Asp Glu Thr Val Thr Ile Glu Thr Val 
                425                 430                 435 

Phe Pro Phe Asp Val Ala Val Lys Phe Val Ser Thr Lys Phe Glu 
                440                 445                 450 

His Leu Glu Arg Val Tyr Ala Asp Ile Pro Phe Leu Leu Met Thr 
                455                 460                 465 

Asp Leu Leu Ser Ala Ser Pro Trp Ala Leu Thr Ile Val Ser Ser 
                470                 475                 480 

Glu Leu Gln Leu Ala Pro Ser Met Thr Thr Val Asp Gln Leu Glu 
                485                 490                 495 

Ser Gln Val Asp Asn Val Ile Leu Gln Thr Gly Glu Ser Ala Ser 
                500                 505                 510 

Glu Cys Phe Cys Leu Gln Cys Pro Ser Leu Gly Asn Ile Glu Gly 
                515                 520                 525 

Gly Val Ala Thr Gly His Tyr Ile Ile Ser Trp Lys Arg Thr Ser 
                530                 535                 540 

Ala Met Glu Asn Ile Pro Ile Ile Thr Thr Val Ile Thr Leu Pro 
                545                 550                 555 

His Val Ile Val Glu Asn Ile Pro Leu His Val Asn Ala Asp Leu 
                560                 565                 570 

Pro Ser Phe Gly Arg Val Arg Glu Ser Leu Pro Val Lys Tyr His 
                575                 580                 585 

Leu Gln Asn Lys Thr Asp Leu Val Gln Asp Val Glu Ile Ser Val 
                590                 595                 600 

Glu Pro Ser Asp Ala Phe Met Phe Ser Gly Leu Lys Gln Ile Arg 
                605                 610                 615 

Leu Arg Ile Leu Pro Gly Thr Glu Gln Glu Met Leu Tyr Asn Phe 
                620                 625                 630 

Tyr Pro Leu Met Ala Gly Tyr Gln Gln Leu Pro Ser Leu Asn Ile 
                635                 640                 645 

Asn Leu Leu Arg Phe Pro Asn Phe Thr Asn Gln Leu Leu Arg Arg 
                650                 655                 660 

Phe Ile Pro Thr Ser Ile Phe Val Lys Pro Gln Gly Arg Leu Met 
                665                 670                 675 

Asp Asp Thr Ser Ile Ala Ala Ala 
                680 

 
           
             4  
             1150  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1965924CD1  
             
           
            4 

Met Ala Gln Phe Gly Gly Gln Lys Asn Pro Pro Trp Ala Thr Gln 
  1               5                  10                  15 

Phe Thr Ala Thr Ala Val Ser Gln Pro Ala Ala Leu Gly Val Gln 
                 20                  25                  30 

Gln Pro Ser Leu Leu Gly Ala Ser Pro Thr Ile Tyr Thr Gln Gln 
                 35                  40                  45 

Thr Ala Leu Ala Ala Ala Gly Leu Thr Thr Gln Thr Pro Ala Asn 
                 50                  55                  60 

Tyr Gln Leu Thr Gln Thr Ala Ala Leu Gln Gln Gln Ala Ala Ala 
                 65                  70                  75 

Ala Ala Ala Ala Leu Gln Gln Gln Tyr Ser Gln Pro Gln Gln Ala 
                 80                  85                  90 

Leu Tyr Ser Val Gln Gln Gln Leu Gln Gln Pro Gln Gln Thr Leu 
                 95                 100                 105 

Leu Thr Gln Pro Ala Val Ala Leu Pro Thr Ser Leu Ser Leu Ser 
                110                 115                 120 

Thr Pro Gln Pro Thr Ala Gln Ile Thr Val Ser Tyr Pro Thr Pro 
                125                 130                 135 

Arg Ser Ser Gln Gln Gln Thr Gln Pro Gln Lys Gln Arg Val Phe 
                140                 145                 150 

Thr Gly Val Val Thr Lys Leu His Asp Thr Phe Gly Phe Val Asp 
                155                 160                 165 

Glu Asp Val Phe Phe Gln Leu Ser Ala Val Lys Gly Lys Thr Pro 
                170                 175                 180 

Gln Val Gly Asp Arg Val Leu Val Glu Ala Thr Tyr Asn Pro Asn 
                185                 190                 195 

Met Pro Phe Lys Trp Asn Ala Gln Arg Ile Gln Thr Leu Pro Asn 
                200                 205                 210 

Gln Asn Gln Ser Gln Thr Gln Pro Leu Leu Lys Thr Pro Pro Ala 
                215                 220                 225 

Val Leu Gln Pro Ile Ala Pro Gln Thr Thr Phe Gly Val Gln Thr 
                230                 235                 240 

Gln Pro Gln Pro Gln Ser Leu Leu Gln Ala Gln Ile Ser Ala Ala 
                245                 250                 255 

Ser Ile Thr Pro Leu Leu Gln Thr Gln Pro Gln Pro Leu Leu Gln 
                260                 265                 270 

Gln Pro Gln Gln Lys Ala Gly Leu Leu Gln Pro Pro Val Arg Ile 
                275                 280                 285 

Val Ser Gln Pro Gln Pro Ala Arg Arg Leu Asp Pro Pro Ser Arg 
                290                 295                 300 

Phe Ser Gly Arg Asn Asp Arg Gly Asp Gln Val Pro Asn Arg Lys 
                305                 310                 315 

Asp Asp Arg Ser Arg Glu Arg Glu Arg Glu Arg Arg Arg Ser Arg 
                320                 325                 330 

Glu Arg Ser Pro Gln Arg Lys Arg Ser Arg Glu Arg Ser Pro Arg 
                335                 340                 345 

Arg Glu Arg Glu Arg Ser Pro Arg Arg Val Arg Arg Val Val Pro 
                350                 355                 360 

Arg Tyr Thr Val Gln Phe Ser Lys Phe Ser Leu Asp Cys Pro Ser 
                365                 370                 375 

Cys Asp Met Met Glu Leu Arg Arg Arg Tyr Gln Asn Leu Tyr Ile 
                380                 385                 390 

Pro Ser Asp Phe Phe Asp Ala Gln Phe Thr Trp Val Asp Ala Phe 
                395                 400                 405 

Pro Leu Ser Arg Pro Phe Gln Leu Gly Asn Tyr Cys Asn Phe Tyr 
                410                 415                 420 

Val Met His Arg Glu Val Glu Ser Leu Glu Lys Asn Met Ala Ile 
                425                 430                 435 

Leu Asp Pro Pro Asp Ala Asp His Leu Tyr Ser Ala Lys Val Met 
                440                 445                 450 

Leu Met Ala Ser Pro Ser Met Glu Asp Leu Tyr His Lys Ser Cys 
                455                 460                 465 

Ala Leu Ala Glu Asp Pro Gln Glu Leu Arg Asp Gly Phe Gln His 
                470                 475                 480 

Pro Ala Arg Leu Val Lys Phe Leu Val Gly Met Lys Gly Lys Asp 
                485                 490                 495 

Glu Ala Met Ala Ile Gly Gly His Trp Ser Pro Ser Leu Asp Gly 
                500                 505                 510 

Pro Asp Pro Glu Lys Asp Pro Ser Val Leu Ile Lys Thr Ala Ile 
                515                 520                 525 

Arg Cys Cys Lys Ala Leu Thr Gly Ile Asp Leu Ser Val Cys Thr 
                530                 535                 540 

Gln Trp Tyr Arg Phe Ala Glu Ile Arg Tyr His Arg Pro Glu Glu 
                545                 550                 555 

Thr His Lys Gly Arg Thr Val Pro Ala His Val Glu Thr Val Val 
                560                 565                 570 

Leu Phe Phe Pro Asp Val Trp His Cys Leu Pro Thr Arg Ser Glu 
                575                 580                 585 

Trp Glu Thr Leu Ser Arg Gly Tyr Lys Gln Gln Leu Val Glu Lys 
                590                 595                 600 

Leu Gln Gly Glu Arg Lys Glu Ala Asp Gly Glu Gln Asp Glu Glu 
                605                 610                 615 

Glu Lys Asp Asp Gly Glu Ala Lys Glu Ile Ser Thr Pro Thr His 
                620                 625                 630 

Trp Ser Lys Leu Asp Pro Lys Thr Met Lys Val Asn Asp Leu Arg 
                635                 640                 645 

Lys Glu Leu Glu Ser Arg Ala Leu Ser Ser Lys Gly Leu Lys Ser 
                650                 655                 660 

Gln Leu Ile Ala Arg Leu Thr Lys Gln Leu Lys Val Glu Glu Gln 
                665                 670                 675 

Lys Glu Glu Gln Lys Glu Leu Glu Lys Ser Glu Lys Glu Glu Asp 
                680                 685                 690 

Glu Asp Asp Asp Arg Lys Ser Glu Asp Asp Lys Glu Glu Glu Glu 
                695                 700                 705 

Arg Lys Arg Gln Glu Glu Ile Glu Arg Gln Arg Arg Glu Arg Arg 
                710                 715                 720 

Tyr Ile Leu Pro Asp Glu Pro Ala Ile Ile Val His Pro Asn Trp 
                725                 730                 735 

Ala Ala Lys Ser Gly Lys Phe Asp Cys Ser Ile Met Ser Leu Ser 
                740                 745                 750 

Val Leu Leu Asp Tyr Arg Leu Glu Asp Asn Lys Glu His Ser Phe 
                755                 760                 765 

Glu Val Ser Leu Phe Ala Glu Leu Phe Asn Glu Met Leu Gln Arg 
                770                 775                 780 

Asp Phe Gly Val Arg Ile Tyr Lys Ser Leu Leu Ser Leu Pro Glu 
                785                 790                 795 

Lys Glu Asp Lys Lys Glu Lys Asp Lys Lys Ser Lys Lys Asp Glu 
                800                 805                 810 

Arg Lys Asp Lys Lys Glu Glu Arg Asp Asp Glu Thr Asp Glu Pro 
                815                 820                 825 

Lys Pro Lys Arg Arg Lys Ser Gly Asp Asp Lys Asp Lys Lys Glu 
                830                 835                 840 

Asp Arg Asp Glu Arg Lys Lys Glu Asp Lys Arg Lys Asp Asp Ser 
                845                 850                 855 

Lys Asp Asp Asp Glu Thr Glu Glu Asp Asn Asn Gln Asp Glu Tyr 
                860                 865                 870 

Asp Pro Met Glu Ala Glu Glu Ala Glu Asp Glu Glu Asp Asp Arg 
                875                 880                 885 

Asp Glu Glu Glu Met Thr Lys Arg Asp Asp Lys Arg Asp Ile Asn 
                890                 895                 900 

Arg Tyr Cys Lys Glu Arg Pro Ser Lys Asp Lys Glu Lys Glu Lys 
                905                 910                 915 

Thr Gln Met Ile Thr Ile Asn Arg Asp Leu Leu Met Ala Phe Val 
                920                 925                 930 

Tyr Phe Asp Gln Ser His Cys Gly Tyr Leu Leu Glu Lys Asp Leu 
                935                 940                 945 

Glu Glu Ile Leu Tyr Thr Leu Gly Leu His Leu Ser Arg Ala Gln 
                950                 955                 960 

Val Lys Lys Leu Leu Asn Lys Val Val Leu Arg Glu Ser Cys Phe 
                965                 970                 975 

Tyr Arg Lys Leu Thr Asp Thr Ser Lys Asp Glu Glu Asn His Glu 
                980                 985                 990 

Glu Ser Glu Ser Leu Gln Glu Asp Met Leu Gly Asn Arg Leu Leu 
                995                1000                1005 

Leu Pro Thr Pro Thr Val Lys Gln Glu Ser Lys Asp Val Glu Glu 
               1010                1015                1020 

Asn Val Gly Leu Ile Val Tyr Asn Gly Ala Met Val Asp Val Gly 
               1025                1030                1035 

Ser Leu Leu Gln Lys Leu Glu Lys Ser Glu Lys Val Arg Ala Glu 
               1040                1045                1050 

Val Glu Gln Lys Leu Gln Leu Leu Glu Glu Lys Thr Asp Glu Asp 
               1055                1060                1065 

Glu Lys Thr Ile Leu Asn Leu Glu Asn Ser Asn Lys Ser Leu Ser 
               1070                1075                1080 

Gly Glu Leu Arg Glu Val Lys Lys Asp Leu Ser Gln Leu Gln Glu 
               1085                1090                1095 

Asn Leu Lys Ile Ser Glu Asn Met Asn Leu Gln Phe Glu Asn Gln 
               1100                1105                1110 

Met Asn Lys Thr Ile Arg Asn Leu Ser Thr Val Met Asp Glu Ile 
               1115                1120                1125 

His Thr Val Leu Lys Lys Asp Asn Val Lys Asn Glu Asp Lys Asp 
               1130                1135                1140 

Gln Lys Ser Lys Glu Asn Gly Ala Ser Val 
               1145                1150 

 
           
             5  
             349  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2073295CD1  
             
           
            5 

Met Ala Ile Pro Ile Thr Val Leu Asp Cys Asp Leu Leu Leu Tyr 
  1               5                  10                  15 

Gly Arg Gly His Arg Thr Leu Asp Arg Phe Lys Leu Asp Asp Val 
                 20                  25                  30 

Thr Asp Glu Tyr Leu Met Ser Met Tyr Gly Phe Pro Arg Gln Phe 
                 35                  40                  45 

Ile Tyr Tyr Leu Val Glu Leu Leu Gly Ala Asn Leu Ser Arg Pro 
                 50                  55                  60 

Thr Gln Arg Ser Arg Ala Ile Ser Pro Glu Thr Gln Val Leu Ala 
                 65                  70                  75 

Ala Leu Gly Phe Tyr Thr Ser Gly Ser Phe Gln Thr Arg Met Gly 
                 80                  85                  90 

Asp Ala Ile Gly Ile Ser Gln Ala Ser Met Ser Arg Cys Val Ala 
                 95                 100                 105 

Asn Val Thr Glu Ala Leu Val Glu Arg Ala Ser Gln Phe Ile Arg 
                110                 115                 120 

Phe Pro Ala Asp Glu Ala Ser Ile Gln Ala Leu Lys Asp Glu Phe 
                125                 130                 135 

Tyr Gly Leu Ala Gly Met Pro Gly Val Met Gly Val Val Asp Cys 
                140                 145                 150 

Ile His Val Ala Ile Lys Ala Pro Asn Ala Glu Asp Leu Ser Tyr 
                155                 160                 165 

Val Asn Arg Lys Gly Leu His Ser Leu Asn Cys Leu Met Val Cys 
                170                 175                 180 

Asp Ile Arg Gly Thr Leu Met Thr Val Glu Thr Asn Trp Pro Gly 
                185                 190                 195 

Ser Leu Gln Asp Cys Ala Val Leu Gln Gln Ser Ser Leu Ser Ser 
                200                 205                 210 

Gln Phe Glu Ala Gly Met His Lys Asp Ser Trp Leu Leu Gly Asp 
                215                 220                 225 

Ser Ser Phe Phe Leu Arg Thr Trp Leu Met Thr Pro Leu His Ile 
                230                 235                 240 

Pro Glu Thr Pro Ala Glu Tyr Arg Tyr Asn Met Ala His Ser Ala 
                245                 250                 255 

Thr His Ser Val Ile Glu Lys Thr Phe Arg Thr Leu Cys Ser Arg 
                260                 265                 270 

Phe Arg Cys Leu Asp Gly Ser Lys Gly Ala Leu Gln Tyr Ser Pro 
                275                 280                 285 

Glu Lys Ser Ser His Ile Ile Leu Ala Cys Cys Val Leu His Asn 
                290                 295                 300 

Ile Ser Leu Glu His Gly Met Asp Val Trp Ser Ser Pro Met Thr 
                305                 310                 315 

Gly Pro Met Glu Gln Pro Pro Glu Glu Glu Tyr Glu His Met Glu 
                320                 325                 330 

Ser Leu Asp Leu Glu Ala Asp Arg Ile Arg Gln Glu Leu Met Leu 
                335                 340                 345 

Thr His Phe Ser 

 
           
             6  
             510  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3054202CD1  
             
           
            6 

Met Ala Lys Ile Leu Lys Tyr Gln Thr Met Arg Arg His Glu Glu 
  1               5                  10                  15 

Thr Trp Ala Glu Ser Leu Arg Tyr Arg Arg Pro Asp Leu Asp Cys 
                 20                  25                  30 

Met Ala Gly Leu Arg Arg Ile Thr Leu Asn Cys Asn Thr Leu Ile 
                 35                  40                  45 

Gly Asp Leu Gly Ala Cys Ala Phe Ala Asp Ser Leu Ser Glu Asp 
                 50                  55                  60 

Leu Trp Leu Arg Ala Leu Asp Leu Gln Gln Cys Gly Leu Thr Asn 
                 65                  70                  75 

Glu Gly Ala Lys Ala Leu Leu Glu Ala Leu Glu Thr Asn Thr Thr 
                 80                  85                  90 

Leu Val Val Leu Asp Ile Arg Lys Asn Pro Leu Ile Asp His Ser 
                 95                 100                 105 

Met Met Lys Ala Val Ile Lys Lys Val Leu Gln Asn Gly Arg Ser 
                110                 115                 120 

Ala Lys Ser Glu Tyr Gln Trp Ile Thr Ser Pro Ser Val Lys Glu 
                125                 130                 135 

Pro Ser Lys Thr Ala Lys Gln Lys Arg Arg Thr Ile Ile Leu Gly 
                140                 145                 150 

Ser Gly His Lys Gly Lys Ala Thr Ile Arg Ile Gly Leu Ala Thr 
                155                 160                 165 

Lys Lys Pro Val Ser Ser Gly Arg Lys His Ser Leu Gly Lys Glu 
                170                 175                 180 

Tyr Tyr Ala Pro Ala Pro Leu Pro Pro Gly Val Ser Gly Phe Leu 
                185                 190                 195 

Pro Trp Arg Thr Ala Glu Arg Ala Lys Arg His Arg Gly Phe Pro 
                200                 205                 210 

Leu Ile Lys Thr Arg Asp Ile Cys Asn Gln Leu Gln Gln Pro Gly 
                215                 220                 225 

Phe Pro Val Thr Val Thr Val Glu Ser Pro Ser Ser Ser Glu Val 
                230                 235                 240 

Glu Glu Val Asp Asp Ser Ser Glu Ser Val His Glu Val Pro Glu 
                245                 250                 255 

Lys Thr Ser Ile Glu Gln Glu Ala Leu Gln Glu Lys Leu Glu Glu 
                260                 265                 270 

Cys Leu Lys Gln Leu Lys Glu Glu Arg Val Ile Arg Leu Lys Val 
                275                 280                 285 

Asp Lys Arg Val Ser Glu Leu Glu His Glu Asn Ala Gln Leu Arg 
                290                 295                 300 

Asn Ile Asn Phe Ser Leu Ser Glu Ala Leu His Ala Gln Ser Leu 
                305                 310                 315 

Thr Asn Met Ile Leu Asp Asp Glu Gly Val Leu Gly Ser Ile Glu 
                320                 325                 330 

Asn Ser Phe Gln Lys Phe His Ala Phe Leu Asp Leu Leu Lys Asp 
                335                 340                 345 

Ala Gly Leu Gly Gln Leu Ala Thr Met Ala Gly Ile Asp Gln Ser 
                350                 355                 360 

Asp Phe Gln Leu Leu Gly His Pro Gln Met Thr Ser Thr Val Ser 
                365                 370                 375 

Asn Pro Pro Lys Glu Glu Lys Lys Ala Leu Glu Asp Glu Lys Pro 
                380                 385                 390 

Glu Pro Lys Gln Asn Ala Leu Gly Gln Met Gln Asn Ile Gln Val 
                395                 400                 405 

Ser Ile Cys Met Gln Ser Ala Tyr Asn Glu Gly Thr Leu Met Lys 
                410                 415                 420 

Phe Gln Lys Ile Thr Gly Asp Ala Arg Ile Pro Leu Pro Leu Asp 
                425                 430                 435 

Ser Phe Pro Val Pro Val Ser Thr Pro Glu Gly Leu Gly Thr Ser 
                440                 445                 450 

Ser Asn Asn Leu Gly Val Pro Ala Thr Glu Gln Arg Gln Glu Ser 
                455                 460                 465 

Phe Glu Gly Phe Ile Ala Arg Met Cys Ser Pro Ser Pro Asp Ala 
                470                 475                 480 

Thr Ser Gly Thr Gly Ser Gln Arg Lys Glu Glu Glu Leu Ser Arg 
                485                 490                 495 

Asn Ser Arg Ser Ser Ser Glu Lys Lys Thr Lys Thr Glu Ser His 
                500                 505                 510 

 
           
             7  
             91  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5316792CD1  
             
           
            7 

Met Arg Met Ser His Ala Gly Cys Pro Glu Arg Ala Ser Arg Gln 
  1               5                  10                  15 

Arg Glu Gln Lys Val Pro Ser Ser Pro Ser Ser Ala Gly Pro Gly 
                 20                  25                  30 

Thr Phe Ser Ser Ala Phe Tyr Ser Gln Ser His Cys Ser Ala Thr 
                 35                  40                  45 

His Phe Ser Phe Leu Gly Thr Pro Asp Gly Lys Trp Leu Tyr Leu 
                 50                  55                  60 

Phe Ile Pro Ile Ala Leu Gly His Ser Gln Gln Pro Arg Arg His 
                 65                  70                  75 

Glu Ala Pro Ser Arg Pro Cys Leu Thr Ser Ala Pro Val Ala His 
                 80                  85                  90 

Pro 

 
           
             8  
             599  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5572967CD1  
             
           
            8 

Met Ser Gly Pro Cys Gly Glu Lys Pro Val Leu Glu Ala Ser Pro 
  1               5                  10                  15 

Thr Met Ser Leu Trp Glu Phe Glu Asp Ser His Ser Arg Gln Gly 
                 20                  25                  30 

Thr Pro Arg Pro Gly Gln Glu Leu Ala Ala Glu Glu Ala Ser Ala 
                 35                  40                  45 

Leu Glu Leu Gln Met Lys Val Asp Phe Phe Arg Lys Leu Gly Tyr 
                 50                  55                  60 

Ser Ser Thr Glu Ile His Ser Val Leu Gln Lys Leu Gly Val Gln 
                 65                  70                  75 

Ala Asp Thr Asn Thr Val Leu Gly Glu Leu Val Lys His Gly Thr 
                 80                  85                  90 

Ala Thr Glu Arg Glu Arg Gln Thr Ser Pro Asp Pro Cys Pro Gln 
                 95                 100                 105 

Leu Pro Leu Val Pro Arg Gly Gly Gly Thr Pro Lys Ala Pro Asn 
                110                 115                 120 

Leu Glu Pro Pro Leu Pro Glu Glu Glu Lys Glu Gly Ser Asp Leu 
                125                 130                 135 

Arg Pro Val Val Ile Asp Gly Ser Asn Val Ala Met Ser His Gly 
                140                 145                 150 

Asn Lys Glu Val Phe Ser Cys Arg Gly Ile Leu Leu Ala Val Asn 
                155                 160                 165 

Trp Phe Leu Glu Arg Gly His Thr Asp Ile Thr Val Phe Val Pro 
                170                 175                 180 

Ser Trp Arg Lys Glu Gln Pro Arg Pro Asp Val Pro Ile Thr Asp 
                185                 190                 195 

Gln His Ile Leu Arg Glu Leu Glu Lys Lys Lys Ile Leu Val Phe 
                200                 205                 210 

Thr Pro Ser Arg Arg Val Gly Gly Lys Arg Val Val Cys Tyr Asp 
                215                 220                 225 

Asp Arg Phe Ile Val Lys Leu Ala Tyr Glu Ser Asp Gly Ile Val 
                230                 235                 240 

Val Ser Asn Asp Thr Tyr Arg Asp Leu Gln Gly Glu Arg Gln Glu 
                245                 250                 255 

Trp Lys Arg Phe Ile Glu Glu Arg Leu Leu Met Tyr Ser Phe Val 
                260                 265                 270 

Asn Asp Lys Phe Met Pro Pro Asp Asp Pro Leu Gly Arg His Gly 
                275                 280                 285 

Pro Ser Leu Asp Asn Phe Leu Arg Lys Lys Pro Leu Thr Leu Glu 
                290                 295                 300 

His Arg Lys Gln Pro Cys Pro Tyr Gly Arg Lys Cys Thr Tyr Gly 
                305                 310                 315 

Ile Lys Cys Arg Phe Phe His Pro Glu Arg Pro Ser Cys Pro Gln 
                320                 325                 330 

Arg Ser Val Ala Asp Glu Leu Arg Ala Asn Ala Leu Leu Ser Pro 
                335                 340                 345 

Pro Arg Ala Pro Ser Lys Asp Lys Asn Gly Arg Arg Pro Ser Pro 
                350                 355                 360 

Ser Ser Gln Ser Ser Ser Leu Leu Thr Glu Ser Glu Gln Cys Ser 
                365                 370                 375 

Leu Asp Gly Lys Lys Leu Gly Ala Gln Ala Ser Pro Gly Ser Arg 
                380                 385                 390 

Gln Glu Gly Leu Thr Gln Thr Tyr Ala Pro Ser Gly Arg Ser Leu 
                395                 400                 405 

Ala Pro Ser Gly Gly Ser Gly Ser Ser Phe Gly Pro Thr Asp Trp 
                410                 415                 420 

Leu Pro Gln Thr Leu Asp Ser Leu Pro Tyr Val Ser Gln Asp Cys 
                425                 430                 435 

Leu Asp Ser Gly Ile Gly Ser Leu Glu Ser Gln Met Ser Glu Leu 
                440                 445                 450 

Trp Gly Val Arg Gly Gly Gly Pro Gly Glu Pro Gly Pro Pro Arg 
                455                 460                 465 

Ala Pro Tyr Thr Gly Tyr Ser Pro Tyr Gly Ser Glu Leu Pro Ala 
                470                 475                 480 

Thr Ala Ala Phe Ser Ala Phe Gly Arg Ala Met Gly Ala Gly His 
                485                 490                 495 

Phe Ser Val Pro Ala Asp Tyr Pro Pro Ala Pro Pro Ala Phe Pro 
                500                 505                 510 

Pro Arg Glu Tyr Trp Ser Glu Pro Tyr Pro Leu Pro Pro Pro Thr 
                515                 520                 525 

Ser Val Leu Gln Glu Pro Pro Val Gln Ser Pro Gly Ala Gly Arg 
                530                 535                 540 

Ser Pro Trp Gly Arg Ala Gly Ser Leu Ala Lys Glu Gln Ala Ser 
                545                 550                 555 

Val Tyr Thr Lys Leu Cys Gly Val Phe Pro Pro His Leu Val Glu 
                560                 565                 570 

Ala Val Met Gly Arg Phe Pro Gln Leu Leu Asp Pro Gln Gln Leu 
                575                 580                 585 

Ala Ala Glu Ile Leu Ser Tyr Lys Ser Gln His Pro Ser Glu 
                590                 595 

 
           
             9  
             128  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7473247CD1  
             
           
            9 

Met Leu Gly Pro Gly Ser Asn Arg Arg Arg Pro Thr Gln Gly Glu 
  1               5                  10                  15 

Arg Gly Pro Gly Ser Pro Gly Glu Pro Met Glu Lys Tyr Gln Val 
                 20                  25                  30 

Leu Tyr Gln Leu Asn Pro Gly Ala Leu Gly Val Asn Leu Val Val 
                 35                  40                  45 

Glu Glu Met Glu Thr Lys Val Lys His Val Ile Lys Gln Val Glu 
                 50                  55                  60 

Cys Met Asp Asp His Tyr Ala Ser Gln Ala Leu Glu Glu Gly Thr 
                 65                  70                  75 

Glu Ala Met His Leu Arg Lys Ser Leu Arg Gln Ser Pro Gly Ser 
                 80                  85                  90 

Leu Lys Ala Val Leu Lys Thr Met Glu Glu Lys Gln Ile Pro Asp 
                 95                 100                 105 

Val Glu Thr Phe Arg Asn Leu Leu Pro Leu Met Leu Gln Ile Asp 
                110                 115                 120 

Pro Ser Asp Arg Ile Thr Ile Lys 
                125 

 
           
             10  
             859  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7482930CD1  
             
           
            10 

Met Asp Ala Asn Lys Asn Lys Ile Lys Leu Gly Ile Cys Lys Ala 
  1               5                  10                  15 

Ala Thr Glu Glu Glu Asn Ser His Gly Gln Ala Asn Gly Leu Leu 
                 20                  25                  30 

Asn Ala Pro Ser Leu Gly Ser Pro Ile Arg Val Arg Ser Glu Ile 
                 35                  40                  45 

Thr Gln Pro Asp Arg Asp Ile Pro Leu Val Arg Lys Leu Arg Ser 
                 50                  55                  60 

Ile His Ser Phe Glu Leu Glu Lys Arg Leu Thr Leu Glu Pro Lys 
                 65                  70                  75 

Pro Asp Thr Asp Lys Phe Leu Glu Thr Cys Leu Glu Lys Met Gln 
                 80                  85                  90 

Lys Asp Thr Ser Ala Gly Lys Glu Ser Ile Leu Pro Ala Leu Leu 
                 95                 100                 105 

His Lys Pro Cys Val Pro Ala Val Ser Arg Thr Asp His Ile Trp 
                110                 115                 120 

His Tyr Asp Glu Glu Tyr Leu Pro Asp Ala Ser Lys Pro Ala Ser 
                125                 130                 135 

Ala Asn Thr Pro Glu Gln Ala Asp Gly Gly Gly Ser Asn Gly Phe 
                140                 145                 150 

Ile Ala Val Asn Leu Ser Ser Cys Lys Gln Glu Ile Asp Ser Lys 
                155                 160                 165 

Glu Trp Val Ile Val Asp Lys Glu Gln Asp Leu Gln Asp Phe Arg 
                170                 175                 180 

Thr Asn Glu Ala Val Gly His Lys Thr Thr Gly Ser Pro Ser Asp 
                185                 190                 195 

Glu Glu Pro Glu Val Leu Gln Val Leu Glu Ala Ser Pro Gln Asp 
                200                 205                 210 

Glu Lys Leu Gln Leu Gly Pro Trp Ala Glu Asn Asp His Leu Lys 
                215                 220                 225 

Lys Glu Thr Ser Gly Val Val Leu Ala Leu Ser Ala Glu Gly Pro 
                230                 235                 240 

Pro Thr Ala Ala Ser Glu Gln Tyr Thr Asp Arg Leu Glu Leu Gln 
                245                 250                 255 

Pro Gly Ala Ala Ser Gln Phe Ile Ala Ala Thr Pro Thr Ser Leu 
                260                 265                 270 

Met Glu Ala Gln Ala Glu Gly Pro Leu Thr Ala Ile Thr Ile Pro 
                275                 280                 285 

Arg Pro Ser Val Ala Ser Thr Gln Ser Thr Ser Gly Ser Phe His 
                290                 295                 300 

Cys Gly Gln Gln Pro Glu Lys Lys Asp Leu Gln Pro Met Glu Pro 
                305                 310                 315 

Thr Val Glu Leu Tyr Ser Pro Arg Glu Asn Phe Ser Gly Leu Val 
                320                 325                 330 

Val Thr Glu Gly Glu Pro Pro Ser Gly Gly Ser Arg Thr Asp Leu 
                335                 340                 345 

Gly Leu Gln Ile Asp His Ile Gly His Asp Met Leu Pro Asn Ile 
                350                 355                 360 

Arg Glu Ser Asn Lys Ser Gln Asp Leu Gly Pro Lys Glu Leu Pro 
                365                 370                 375 

Asp His Asn Arg Leu Val Val Arg Glu Phe Glu Asn Leu Pro Gly 
                380                 385                 390 

Glu Thr Glu Glu Lys Ser Ile Leu Leu Glu Ser Asp Asn Glu Asp 
                395                 400                 405 

Glu Lys Leu Ser Arg Gly Gln His Cys Ile Glu Ile Ser Ser Leu 
                410                 415                 420 

Pro Gly Asp Leu Val Ile Val Glu Lys Asp His Ser Ala Thr Thr 
                425                 430                 435 

Glu Pro Leu Asp Val Thr Lys Thr Gln Thr Phe Ser Val Val Pro 
                440                 445                 450 

Asn Gln Asp Lys Asn Asn Glu Ile Met Lys Leu Leu Thr Val Gly 
                455                 460                 465 

Thr Ser Glu Ile Ser Ser Arg Asp Ile Asp Pro His Val Glu Gly 
                470                 475                 480 

Gln Ile Gly Gln Val Ala Glu Met Gln Lys Asn Lys Ile Ser Lys 
                485                 490                 495 

Asp Asp Asp Ile Met Ser Glu Asp Leu Pro Gly His Gln Gly Asp 
                500                 505                 510 

Leu Ser Thr Phe Leu His Gln Glu Gly Lys Arg Glu Lys Ile Thr 
                515                 520                 525 

Pro Arg Asn Gly Glu Leu Phe His Cys Val Ser Glu Asn Glu His 
                530                 535                 540 

Gly Ala Pro Thr Arg Lys Asp Met Val Arg Ser Ser Phe Val Thr 
                545                 550                 555 

Arg His Ser Arg Ile Pro Val Leu Ala Gln Glu Ile Asp Ser Thr 
                560                 565                 570 

Leu Glu Ser Ser Ser Pro Val Ser Ala Lys Glu Lys Leu Leu Gln 
                575                 580                 585 

Lys Lys Ala Tyr Gln Pro Asp Leu Val Lys Leu Leu Val Glu Lys 
                590                 595                 600 

Arg Gln Phe Lys Ser Phe Leu Gly Asp Leu Ser Ser Ala Ser Asp 
                605                 610                 615 

Lys Leu Leu Glu Glu Lys Leu Ala Thr Val Pro Ala Pro Phe Cys 
                620                 625                 630 

Glu Glu Glu Val Leu Thr Pro Phe Ser Arg Leu Thr Val Asp Ser 
                635                 640                 645 

His Leu Ser Arg Ser Ala Glu Asp Ser Phe Leu Ser Pro Ile Ile 
                650                 655                 660 

Ser Gln Ser Arg Lys Ser Lys Ile Pro Arg Pro Val Ser Trp Val 
                665                 670                 675 

Asn Thr Asp Gln Val Asn Ser Ser Thr Ser Ser Gln Phe Phe Pro 
                680                 685                 690 

Arg Pro Pro Pro Gly Lys Pro Pro Thr Arg Pro Gly Val Glu Ala 
                695                 700                 705 

Arg Leu Arg Arg Tyr Lys Val Leu Gly Ser Ser Asn Ser Asp Ser 
                710                 715                 720 

Asp Leu Phe Ser Arg Leu Ala Gln Ile Leu Gln Asn Gly Ser Gln 
                725                 730                 735 

Lys Pro Arg Ser Thr Thr Gln Cys Lys Ser Pro Gly Ser Pro His 
                740                 745                 750 

Asn Pro Lys Thr Pro Pro Lys Ser Pro Val Val Pro Arg Arg Ser 
                755                 760                 765 

Pro Ser Ala Ser Pro Arg Ser Ser Ser Leu Pro Arg Thr Ser Ser 
                770                 775                 780 

Ser Ser Pro Ser Arg Ala Gly Arg Pro His His Asp Gln Arg Ser 
                785                 790                 795 

Ser Ser Pro His Leu Gly Arg Ser Lys Ser Pro Pro Ser His Ser 
                800                 805                 810 

Gly Ser Ser Ser Ser Arg Arg Ser Cys Gln Gln Glu His Cys Lys 
                815                 820                 825 

Pro Ser Lys Asn Gly Leu Lys Gly Ser Gly Ser Leu His His His 
                830                 835                 840 

Ser Ala Ser Thr Lys Thr Pro Gln Gly Lys Ser Lys Pro Ala Ser 
                845                 850                 855 

Lys Leu Ser Arg 

 
           
             11  
             484  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2049942CD1  
             
           
            11 

Met Asp Leu Gly Lys Asp Gln Ser His Leu Lys His His Gln Thr 
  1               5                  10                  15 

Pro Asp Pro His Gln Glu Glu Asn His Ser Pro Glu Val Ile Gly 
                 20                  25                  30 

Thr Trp Ser Leu Arg Asn Arg Glu Leu Leu Arg Lys Arg Lys Ala 
                 35                  40                  45 

Glu Val His Glu Lys Glu Thr Ser Gln Trp Leu Phe Gly Glu Gln 
                 50                  55                  60 

Lys Lys Arg Lys Gln Gln Arg Thr Gly Lys Gly Asn Arg Arg Gly 
                 65                  70                  75 

Arg Lys Arg Gln Gln Asn Thr Glu Leu Lys Val Glu Pro Gln Pro 
                 80                  85                  90 

Gln Ile Glu Lys Glu Ile Val Glu Lys Ala Leu Ala Pro Ile Glu 
                 95                 100                 105 

Lys Lys Thr Glu Pro Pro Gly Ser Ile Thr Lys Val Phe Pro Ser 
                110                 115                 120 

Val Ala Ser Pro Gln Lys Val Val Pro Glu Glu His Phe Ser Glu 
                125                 130                 135 

Ile Cys Gln Glu Ser Asn Ile Tyr Gln Glu Asn Phe Ser Glu Tyr 
                140                 145                 150 

Gln Glu Ile Ala Val Gln Asn His Ser Ser Glu Thr Cys Gln His 
                155                 160                 165 

Val Ser Glu Pro Glu Asp Leu Ser Pro Lys Met Tyr Gln Glu Ile 
                170                 175                 180 

Ser Val Leu Gln Asp Asn Ser Ser Lys Ile Cys Gln Asp Met Lys 
                185                 190                 195 

Glu Pro Glu Asp Asn Ser Pro Asn Thr Cys Gln Val Ile Ser Val 
                200                 205                 210 

Ile Gln Asp His Pro Phe Lys Met Tyr Gln Asp Met Ala Lys Arg 
                215                 220                 225 

Glu Asp Leu Ala Pro Lys Met Cys Gln Glu Ala Ala Val Pro Lys 
                230                 235                 240 

Ile Leu Pro Cys Pro Thr Ser Glu Asp Thr Ala Asp Leu Ala Gly 
                245                 250                 255 

Cys Ser Leu Gln Ala Tyr Pro Lys Pro Asp Val Pro Lys Gly Tyr 
                260                 265                 270 

Ile Leu Asp Thr Asp Gln Asn Pro Ala Glu Pro Glu Glu Tyr Asn 
                275                 280                 285 

Glu Thr Asp Gln Gly Ile Ala Glu Thr Glu Gly Leu Phe Pro Lys 
                290                 295                 300 

Ile Gln Glu Ile Ala Glu Pro Lys Asp Leu Ser Thr Lys Thr His 
                305                 310                 315 

Gln Glu Ser Ala Glu Pro Lys Tyr Leu Pro His Lys Thr Cys Asn 
                320                 325                 330 

Glu Ile Ile Val Pro Lys Ala Pro Ser His Lys Thr Ile Gln Glu 
                335                 340                 345 

Thr Pro His Ser Glu Asp Tyr Ser Ile Glu Ile Asn Gln Glu Thr 
                350                 355                 360 

Pro Gly Ser Glu Lys Tyr Ser Pro Glu Thr Tyr Gln Glu Ile Pro 
                365                 370                 375 

Gly Leu Glu Glu Tyr Ser Pro Glu Ile Tyr Gln Glu Thr Ser Gln 
                380                 385                 390 

Leu Glu Glu Tyr Ser Pro Glu Ile Tyr Gln Glu Thr Pro Gly Pro 
                395                 400                 405 

Glu Asp Leu Ser Thr Glu Thr Tyr Lys Asn Lys Asp Val Pro Lys 
                410                 415                 420 

Glu Cys Phe Pro Glu Pro His Gln Glu Thr Gly Gly Pro Gln Gly 
                425                 430                 435 

Gln Asp Pro Lys Ala His Gln Glu Asp Ala Lys Asp Ala Tyr Thr 
                440                 445                 450 

Phe Pro Gln Glu Met Lys Glu Lys Pro Lys Glu Glu Pro Gly Ile 
                455                 460                 465 

Pro Ala Ile Leu Asn Glu Ser His Pro Glu Asn Asp Val Tyr Ser 
                470                 475                 480 

Tyr Val Leu Phe 

 
           
             12  
             631  
             PRT  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2418711CD1  
             
           
            12 

Met Gln Gly Val Gly Leu Ser Arg Val Pro Ser Ser Pro Pro Gly 
  1               5                  10                  15 

Arg Ala Phe Arg Pro Ala Gly Val His Val Phe Gly Leu Cys Ala 
                 20                  25                  30 

Thr Ala Leu Val Thr Asp Val Ile Gln Leu Ala Thr Gly Tyr His 
                 35                  40                  45 

Thr Pro Phe Phe Leu Thr Val Cys Lys Pro Asn Tyr Thr Leu Leu 
                 50                  55                  60 

Gly Thr Ser Cys Glu Val Asn Pro Tyr Ile Thr Gln Asp Ile Cys 
                 65                  70                  75 

Ser Gly His Asp Ile His Ala Ile Leu Ser Ala Arg Lys Thr Phe 
                 80                  85                  90 

Pro Ser Gln His Ala Thr Leu Ser Ala Phe Ala Ala Val Tyr Val 
                 95                 100                 105 

Ser Met Tyr Phe Asn Ser Val Ile Ser Asp Thr Thr Lys Leu Leu 
                110                 115                 120 

Lys Pro Ile Leu Val Phe Ala Phe Ala Ile Ala Ala Gly Val Cys 
                125                 130                 135 

Gly Leu Thr Gln Ile Thr Gln Tyr Arg Ser His Pro Val Asp Val 
                140                 145                 150 

Tyr Ala Gly Phe Leu Ile Gly Ala Gly Ile Ala Ala Tyr Leu Ala 
                155                 160                 165 

Cys His Ala Val Gly Asn Phe Gln Ala Pro Pro Ala Glu Lys Pro 
                170                 175                 180 

Ala Ala Pro Ala Pro Ala Lys Asp Ala Leu Arg Ala Leu Thr Gln 
                185                 190                 195 

Arg Gly His Asp Ser Val Tyr Gln Gln Asn Lys Ser Val Ser Thr 
                200                 205                 210 

Asp Glu Leu Gly Pro Pro Gly Arg Leu Glu Gly Ala Pro Arg Pro 
                215                 220                 225 

Val Ala Arg Glu Lys Thr Ser Leu Gly Ser Leu Lys Arg Ala Ser 
                230                 235                 240 

Val Asp Val Asp Leu Leu Ala Pro Arg Ser Pro Met Ala Lys Glu 
                245                 250                 255 

Asn Met Val Thr Phe Ser His Thr Leu Pro Arg Ala Ser Ala Pro 
                260                 265                 270 

Ser Leu Asp Asp Pro Ala Arg Arg His Met Thr Ile His Val Pro 
                275                 280                 285 

Leu Asp Ala Ser Arg Ser Lys Gln Leu Ile Ser Glu Trp Lys Gln 
                290                 295                 300 

Lys Ser Leu Glu Gly Pro Arg Pro Gly Ala Ala Arg Arg Arg Gln 
                305                 310                 315 

Pro Arg Ala Pro Ala Arg Ala Arg Arg Thr His Gly Gly Gly Gly 
                320                 325                 330 

Gly Arg Gly Gly Gly Arg Arg Gly Arg Gly Gly Gly Gly Arg Gly 
                335                 340                 345 

Gly Gly Arg Gly Pro Gly Pro Ala Leu Ala Leu Pro His Arg Ala 
                350                 355                 360 

Gly Ala Ala Gly Ala Gly Ala Ser Gly His Pro Pro Thr Ala Arg 
                365                 370                 375 

Gly Ala Ala Ala Ala Gly Ala His Pro Gly Gly Gly Arg Ala Gly 
                380                 385                 390 

Gly Gly Arg Pro Val Pro Gln Lys Arg Arg Arg Gly Ala Arg Gln 
                395                 400                 405 

Val Ala His Asp Gly Arg Glu Glu Arg Gly Gly Ser Gly Gln Pro 
                410                 415                 420 

Ser Ala Ala Ala Ala Gly His Arg His Val Gln Gly Ser Gly Arg 
                425                 430                 435 

Ala Gly Pro Gln Gly Gly Arg Asp Gly Val Val Val Gln Arg Gln 
                440                 445                 450 

Leu Arg Leu Leu Ala Val Pro Val Ala Val Gly Pro Arg Leu Arg 
                455                 460                 465 

Gln His Arg Asp His Arg Arg Ala Arg Ala Ala Pro Pro Arg Gly 
                470                 475                 480 

Ala Pro Val Gly Arg Arg Arg Ala Leu Gly Val Glu Gly Gly Gly 
                485                 490                 495 

Arg Arg Gly Gln Gly Gly Gly Arg Arg Arg Leu Arg Ala Gly Gly 
                500                 505                 510 

Pro Gly Ala Arg Leu Pro Arg Arg Gly Gln Ala Pro Gly Arg Val 
                515                 520                 525 

Pro Arg Leu Val Gly Gln Arg Arg Gly Pro Gly Gly Ala Ala Val 
                530                 535                 540 

Arg Gly Arg Gly His Arg Gln Pro Gly His Gly Arg Gly Ala Ala 
                545                 550                 555 

Pro Ala Gly Arg Gly Arg Trp Gly Ala Gly Pro Gly Gln Pro Gly 
                560                 565                 570 

Val His Ala Ala Ala Pro Arg Gly Arg Pro Gly Ala Gly Gly Ala 
                575                 580                 585 

Arg Gly Gly Gly Gly Gly Arg Gly Leu Leu Pro Gln Asp Ala Gly 
                590                 595                 600 

Ala Pro Leu Pro Arg Leu Ala Arg Arg Gly Arg Gly Arg Ala Gly 
                605                 610                 615 

Gly Gly Pro Arg Ala Arg Ala Ala Ala Arg Met Leu Asn Lys Ala 
                620                 625                 630 

Ala 

 
           
             13  
             1892  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2344051CB1  
             
           
            13 

gtctttgaaa atacttcatt ttcttagcat ttcaggagat tataacatcc tgtatttcag     60 

tttctgagag ctttactgac tgatttccct attcaaaaca atcctcattt cctacatttc    120 

tgaagatctc aagatctgga ctactgttga agaaattccc agtaaggctc acttatatct    180 

ttagagatgg caaataacta caagaaaatt gttctactga aaggattaga ggtcatcaat    240 

gattatcatt ttagaattgt taagtcctta ctgagtaacg atttaaaact taatccaaaa    300 

atgaaagaag agtatgacaa aattcagatt gctgacttga tggaggaaaa gttcccaggt    360 

gatgccggtt tgggcaaact aatagaattc ttcaaagaaa taccaacact gggagacctt    420 

gctgaaactc ttaaaagaga aaagttaaaa gttgcaaata aaattgaatc cattccagtc    480 

aaaggaataa tcccatctaa aaagacgaaa cagaaagaag tgtatcctgc tacacctgca    540 

tgcaccccaa gcaaccgtct cacagctaaa ggagcagagg agactcttgg acctcagaaa    600 

agaaaaaaac catctgaaga agagactgga accaaaagga gtaagatgtc caaagagcag    660 

actcggcctt cctgctctgc aggagccagc acgtccacag ccatgggccg ttccccacct    720 

ccccagacct catcatcagc tccacccaac acttcctcaa ctgagagcct aaaaccattg    780 

gccaaccgtc acgcaactgc cagtaaaaat attttccgag aagacccaat aatcgcgatg    840 

gtactaaatg caacaaaagt atttaaatat gaatcctcag aaaatgagca aagaagaatg    900 

tttcatgcta cagtggctac gcagacacag ttctttcatg tgaaggtttt aaacatcaac    960 

ttgaagagga aattcattaa aaagagaatc atcattatat caaattattc caaacgtaat   1020 

agtctcctag aggtgaatga agcctcttct gtatctgaag ctggtcctga ccaaacgttt   1080 

gaggttccaa aggacatcat cagaagagca aagaaaattc cgaagatcaa tattcttcac   1140 

aaacaaactt caggatatat tgtatatgga ttatttatgc tacatacgaa aattgtaaat   1200 

aggaagacga caatctatga aattcaggat aaaacaggaa gtatggctgt agtaggaaaa   1260 

ggagaatgcc acaatatccc ctgtgaaaaa ggagataagc ttcgactctt ctgctttcga   1320 

ctgagaaaga gggaaaatat gtcaaaactg atgtcagaaa tgcatagttt catccagata   1380 

cagaaaaata caaaccagag aagccatgac tccaggagca tggcactacc ccaggaacag   1440 

agtcagcatc caaaaccttc agaggccagc acaaccctac ctgaaagcca tctcaagact   1500 

cctcagatgc caccaacaac cccatccagc agttccttca ccaaggtcac caaggacaag   1560 

gatatcaaat aactactgtt caatctttac tcaagtgtgg aaattttgcc tgaagtcctc   1620 

cacctaaaaa cctgatgcca ttggtaatga tgtttatgaa gataagatca aagcacagaa   1680 

aataatatat gtatatatat gtatatatat ctggttgaaa tactatatat atatatatat   1740 

ataccagcta ttaattctag gaaatggagt attaagggtg cattttattt cattagtttt   1800 

acttttatgc attttcttca tatcatattt tgcattcaga attttcataa tttgaaaaaa   1860 

aataaacttt ttttttctta aaaaaaaaaa aa                                 1892 

 
           
             14  
             2693  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2257655CB1  
             
           
            14 

ctcgcggtgc gcccgggtgg cgggctgctt tccacgcacc tgcacctgcg cagccctcca     60 

aggcgctctt ttggaggagg gacttctctt tcggtaacca gctcccttgc ggatagtcta    120 

tgttctccat ataaacccag cacttccctt aattgagata cgtgggactt cactccgtcc    180 

ccagcccgga accacaagtg agggcactgc gtttcctgat tgacctcttt ggcgattact    240 

tccgcccagg ggcctggaat actggaggcc cttcgacgga gaacaacaag aaaggcactt    300 

ccggtgtctg ttgccaggcg cgggcccagt gggccgtagg ggcgacattg ttgccgtcgt    360 

ctttcccccc ccagtcccgg ggatggagat gtcgggactc agcttttcag agatggaggg    420 

ctgccgtaac ctacttggcc tactggacaa cgacgagatc atggccctat gcgacaccgt    480 

caccaaccgc ctggtgcagc ctcaggaccg ccaagatgct gttcatgcaa tattagcata    540 

cagtcaaagt gcagaagaac ttctgaggcg tagaaaagtc caccgagaag ttatatttaa    600 

gtacttggca acacagggga ttgttatacc tccagctact gaaaaacaca atcttattca    660 

gcatgcaaaa gattactggc aaaagcaacc acaactgaaa ttgaaggaaa cgccagagcc    720 

agttacaaag acagaggaca tccacctatt tcaacagcag gtgaaagaag ataaaaaagc    780 

tgaaaaagtt gattttcgtc gcctaggaga agaattctgt cattggttct ttggacttct    840 

taattctcag aatccttttc taggaccacc tcaagatgaa tggggaccac agcacttctg    900 

gcatgatgtg aagcttaggt tttattacaa cacatcagaa caaaatgtta tggactacca    960 

tggagcagaa atcgtgagcc ttcgtttgct gtcactagta aaagaagaat ttctttttct   1020 

cagccccaac ctagattcac atggactgaa atgtgcatct tctcctcatg ggctggttat   1080 

ggttggagtt gctgggactg tccatcgagg aaacacttgt ttgggcattt ttgaacaaat   1140 

ttttggactc atccgctgcc cttttgtgga gaatacttgg aaaatcaaat ttatcaacct   1200 

gaaaattatg ggagagagtt cccttgctcc tggaacatta ccgaaaccat ctgttaaatt   1260 

tgaacaaagt gatctagagg ccttttataa tgtaatcact gtatgtggta ccaatgaagt   1320 

acgacataat gtaaagcagg cttcggatag tggaactggg gaccaagttt gaggtagtgg   1380 

aaatgagaca ttgctgaaca aaagagaact gggtttacct gaccctctaa agcgctaagt   1440 

actgtcagcc tgaaaaaaat cttctataca gaaactcttc caaatactat atcagtaatg   1500 

tctgaatgat ttcagatgtg aaaattgaca tattttagtt gaaatacctt tctggactac   1560 

agacttacat atcatgtgaa tacttaccta tttctacccg agttgcagca agtattctga   1620 

aagcttaatg caaataaatc ccactttaga tcttacagct aactgtgtgc cttagaaacc   1680 

aggtaatatt ttccttttac ttagtgaata ttctgctaat atctgcactt ttcatgtggg   1740 

aaaggattaa taatggtcca ggcttcccct ctttaagttt catgtttact tttgtctaac   1800 

tctggataat tgtattttac aaatgcatct cactgtaata tatttttaaa actattaaat   1860 

attttagaga tgtttaacgt aaactcaaag ttctcatttt agaaaattta aataacattc   1920 

tttttgcaaa aaagtccaat aatttaacag ttgaagaaaa acttactacc tctttaaata   1980 

tttgagaaac atttttcaaa gttatcagct gtagtccaag ctaaatatct tttgtaatct   2040 

gcaacatttt ccttactgtt tttgggcagt gataaatgct gttctcgaaa tagactttat   2100 

tcttacctag gcttcagaca acagttttat agagcagtta ctgtaataca atataaagga   2160 

aatatgctgt tgaaatttta aaggtatgcc cagttcctaa cttttaaacg aattaccgtt   2220 

cttcctcttg gctgatcttg gcagagatga caaaaaaaac cccaaaacaa cccatgcatg   2280 

tataatgtgt gtatacacat atacataagt atacatatac tcccacatta taacttagaa   2340 

tatttagttt tttacctgtt actaggtttg agttacatgg ttgagttgcc aaattattta   2400 

catgctttgt ttaaattctt catcacctag caactgtttg ctgatcatgg atttacttag   2460 

ttactttaat ttataaaatt accatttgga aaagaactca attgggaaat gtgatgacgt   2520 

attgtacatg ttactttttc ctttgctata atcatctagg gagactgata agaattttgg   2580 

aaatgggagc ctggaaactc atctttgttt ttttaatgct atgcctctta cgaggaatac   2640 

gaattggtat gtcctaaaat aagaacttaa taaaggaggg aaatcccaaa aaa          2693 

 
           
             15  
             2351  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1520554CB1  
             
           
            15 

cagatgatcg gtgattatag aagagctatg acgtcctgcc gcgtacgtag ctcggaatcg     60 

gctcgagctc tgagaatcat actcttctga gcaagctgtg cacagttcaa gaagtatagt    120 

gcccgcgaat gaaaagtcac ctaatggttc agatgggaga ggaatattat tacgcaaagg    180 

attataccaa agctttgaag ttgctggatt atgtgatgtg tgattatcgg agtgaaggat    240 

ggtggactct gctcacttct gtattaacta cagctctgaa gtgctcctac ctcatggccc    300 

aattaaagga ttacattact tactccctag aactccttgg tagagcttca actctgaaag    360 

atgaccagaa gtctcggata gaaaagaacc tcataaatgt tttaatgaat gaaagtcctg    420 

atccagaacc cgactgtgat atcttagctg tgaaaactgc tcagaagctg tgggcagacc    480 

gaatttctct ggctggcagc aatattttca caataggagt acaggacttt gtgccatttg    540 

tgcagtgcaa agccaagttt catgccccaa gttttcatgt tgatgttcct gttcagtttg    600 

atatttatct gaaggctgat tgtccacatc ccattaggtt ttccaagctc tgtgtcagct    660 

ttaataatca ggaatacaac cagttctgtg taatagaaga agcatccaaa gcaaatgaag    720 

ttttagaaaa tctgactcaa ggaaagatgt gcctagttcc tggcaaaaca agaaaactgt    780 

tatttaagtt tgttgcaaaa actgaagatg tgggaaagaa aattgagatt acttcagtgg    840 

atcttgctct gggcaatgag acgggaagat gtgtggtttt aaattggcag ggaggaggag    900 

gagatgctgc ttcctcccaa gaagccttac aggcagctcg gtctttcaaa aggcgaccta    960 

agctacctga caatgaagtt cactgggaca gcattataat tcaggcaagc acaatgatca   1020 

tatccagagt cccaaacatt tctgtacatc tgctacatga accccctgca ctgactaatg   1080 

aaatgtattg tttggttgtg actgttcagt cccatgaaaa gacccaaatc agagatgtga   1140 

agctcaccgc tggcttaaaa ccaggacagg atgccaattt aactcagaag actcacgtga   1200 

ctcttcatgg aacagaactg tgtgatgaat cctacccggc tttactcact gacattcctg   1260 

ttggagactt acatccaggg gaacagctgg aaaaaatgtt gtatgttcgc tgtggaacag   1320 

tgggttccag aatgtttctt gtatatgttt cttacctgat aaatacaacc gttgaagaaa   1380 

aagaaattgt ttgcaagtgt cacaaggatg aaactgtaac aattgaaaca gtctttccat   1440 

ttgatgttgc ggttaaattt gtttctacca agtttgagca cctggaaagg gtttatgctg   1500 

acatcccctt tctgttgatg acggacctct taagtgcctc accctgggcc ctcactattg   1560 

tttccagtga gctccagctt gctccatcca tgaccacagt ggaccagctc gagtctcaag   1620 

tggacaatgt tatcttacag actggagaga gtgctagtga atgcttttgt cttcaatgcc   1680 

catctcttgg aaatattgaa ggtggagtag caaccgggca ttatattatc tcttggaaaa   1740 

ggacctcagc aatggagaat atccccatca tcacaactgt catcactctg ccgcacgtga   1800 

ttgtggagaa tatccctctc catgtgaatg cagatctgcc gtcatttggg cgtgtcagag   1860 

agtcgttacc tgtcaagtat cacctacaga ataagaccga cttagttcaa gatgtagaaa   1920 

tttctgtgga gcccagtgat gccttcatgt tctcaggtct caaacagatt cgattacgta   1980 

tcctccctgg cacggagcag gaaatgctat ataatttcta tcctctgatg gctggatacc   2040 

agcagctgcc atctctcaac atcaacttgc ttagatttcc taacttcaca aatcagctgc   2100 

tcaggcgttt tatacctacc agtatttttg tcaagccaca gggtcgactc atggatgata   2160 

cctctattgc tgctgcatga tgttcaagac cggcccttgg ctgttgttac agagatgttg   2220 

ggcagagcta tgcaggtgtt tcattgtgaa ctctagcttt gatcatggta aaaagttaac   2280 

cttttctatt ttttaatgga tgttatacca actattcaga ggaactcata cttcaaaaat   2340 

attaggaaaa c                                                        2351 

 
           
             16  
             3827  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 1965924CB1  
             
           
            16 

ggcttcgatg ttagccggga cccgactcag atcgatgcta tagaagacaa acaagggaag     60 

gttttttttc cttttgcatc atggctcaat ttggaggaca gaagaatccg ccatgggcta    120 

ctcagtttac agccactgca gtatcacagc cagctgcact gggtgttcaa cagccatcac    180 

tccttggagc atctcctacc atttatacac agcaaactgc attggcagca gcaggcctta    240 

ccacacaaac tccagcaaac tatcagttaa cacaaactgc tgcattgcag caacaagccg    300 

cagctgcagc agctgcatta caacagcaat attcacaacc tcagcaggcc ctgtatagtg    360 

tgcaacaaca gttacagcaa ccccagcaaa ccctcttaac acagccagct gttgcactgc    420 

ctacaagcct tagcctgtct actcctcagc caacagcaca aataactgta tcatatccaa    480 

caccaaggtc cagtcaacag caaacccagc ctcagaagca gcgtgttttc acaggggtgg    540 

ttacaaaact acatgataca tttggatttg tggatgaaga tgtattcttt cagcttagtg    600 

ctgtcaaagg gaaaaccccc caagtaggtg acagagtatt ggttgaagct acttataatc    660 

ctaatatgcc ttttaaatgg aatgcacaga gaattcaaac actaccaaat cagaatcagt    720 

cgcaaaccca gccattactg aagactcctc ctgctgtact tcagccaatt gcaccacaga    780 

caacatttgg tgttcagact cagccccagc cccagtcact gctgcaggca cagatttcag    840 

cagcttctat tacaccacta ttgcagactc aaccacagcc cttattacag cagcctcagc    900 

aaaaagctgg tttattgcag cctcctgttc gtatagtttc acagccacaa ccggcacgac    960 

gattagatcc cccatcccga ttttcaggaa gaaatgacag aggggatcaa gtgcctaaca   1020 

gaaaagatga tcgaagtcgt gagagagaga gagaaagacg tagatcgaga gaaagatcac   1080 

ctcagaggaa acgttcccgg gaaagatctc cacgaagaga gcgagagcga tcacctcgga   1140 

gagttcgacg tgttgttcca cgttacacag ttcagttttc aaagttttct ttagattgtc   1200 

ccagttgtga catgatggaa ctaaggcgcc gttatcaaaa tttgtatata cctagtgact   1260 

tttttgatgc tcaatttaca tgggtggatg ctttcccttt gtcaagacca tttcagctgg   1320 

gaaattactg caatttttat gtaatgcaca gagaagtaga gtccttagaa aaaaatatgg   1380 

ccattcttga tccaccagat gctgaccact tatacagtgc aaaggtaatg ctgatggcta   1440 

gccctagtat ggaagattta tatcataagt catgtgctct tgctgaggac ccacaagaac   1500 

ttcgagatgg attccaacat cctgctagac ttgttaagtt tttagtgggc atgaaaggca   1560 

aggatgaagc tatggccatt ggaggccact ggtctccttc gttggatgga ccagacccag   1620 

aaaaagatcc ctctgtgttg attaagactg ctattcgttg ttgtaaggct ctgacaggca   1680 

ttgatctaag tgtgtgcaca caatggtacc gttttgcaga gattcgctac catcgccctg   1740 

aggagaccca caaggggcgt acagttccag ctcatgtgga gacagtggtt ttatttttcc   1800 

cggatgtttg gcattgcctt cccacccgct cagagtggga aaccctctcc cgaggataca   1860 

agcagcagct ggtcgagaag cttcagggtg aacgcaagga ggctgatgga gaacaggatg   1920 

aagaagagaa ggatgatggt gaagctaaag aaatttctac acctacccat tggtctaaac   1980 

ttgatccaaa gacaatgaag gtaaatgacc tccgaaaaga attagaaagt cgagctctta   2040 

gttccaaagg attaaaatcc cagttaatag cccgattgac aaaacagctt aaagtagagg   2100 

aacaaaaaga agaacagaag gagttagaga aatctgaaaa agaagaggat gaggatgatg   2160 

ataggaaatc tgaagacgat aaagaggaag aagaaaggaa acgtcaagag gaaatagaac   2220 

gccagcgtcg agaaagaaga tatattttgc ctgatgaacc ggccatcatt gtacatccaa   2280 

attgggctgc aaaaagtggc aagtttgatt gtagcatcat gtctttgagt gtcctattgg   2340 

actacagatt agaggataat aaagaacatt catttgaggt ttcattgttt gcggaacttt   2400 

tcaacgaaat gcttcaaaga gattttggtg tccgtatata caaatcatta ctgtctcttc   2460 

ctgagaaaga ggacaaaaaa gaaaaggata aaaaaagcaa aaaagatgag agaaaagata   2520 

aaaaagaaga aagagatgat gaaactgatg aaccaaaacc caaacggaga aaatcaggcg   2580 

atgataaaga taaaaaagaa gatagagatg aaaggaagaa agaagataaa agaaaagatg   2640 

attctaaaga tgatgatgaa actgaagaag ataacaatca agatgaatat gaccctatgg   2700 

aagcagaaga agctgaggat gaagaagatg atagggatga ggaagaaatg accaaacgag   2760 

atgacaaaag agatatcaac agatactgca aggagaggcc ctctaaagat aaggaaaaag   2820 

aaaagactca aatgatcaca attaacagag atctgttaat ggcttttgtt tattttgatc   2880 

aaagtcattg tggttacctt cttgaaaagg atttggaaga aatactttat actcttggac   2940 

tacatctttc tcgggctcag gtaaagaagc ttcttaataa agtagtgctc cgtgaatctt   3000 

gcttttaccg gaaattaaca gacacctcaa aagatgaaga gaaccatgaa gagtctgagt   3060 

cattgcagga agatatgcta ggaaacagat tattacttcc aacaccaaca gtaaagcagg   3120 

aatcaaagga tgtggaagaa aatgttggcc tcattgtgta caatggtgca atggtagatg   3180 

taggaagcct cttgcaaaaa ttggaaaaga gcgaaaaagt aagagctgag gtagaacaga   3240 

agctgcagtt actagaagaa aaaacagatg aagatgaaaa aaccatatta aatttggaga   3300 

attccaacaa aagcctctct ggtgaactca gagaagttaa aaaggacctt agtcagttac   3360 

aagaaaactt aaagatttcg gaaaacatga atttacaatt tgaaaaccaa atgaataaga   3420 

caatcagaaa cttatctacg gtaatggatg aaatccacac tgttctcaag aaggataatg   3480 

taaagaatga agacaaagat caaaaatcca aggagaatgg tgccagtgta tgataaaatc   3540 

catgtagtga tgaggaatgg tgttaaataa tgtaatatat aaaaatcatg atataagaat   3600 

gtttgaaggt gatgcatgtt tgattttagt agtataaatg tattttagtt caaatgatgt   3660 

ataaagtttt atgaatgtga gtttctgctt ttgaaaattg cttgtaattc ctagccttca   3720 

aattattaaa cactccttga gtgaaataat tttgcattgc aaagtgtttt aggatgaact   3780 

ttgttatagt tttaactcca ataaagttca tcagtttaaa aaaaaaa                 3827 

 
           
             17  
             2193  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2073295CB1  
             
           
            17 

gcgccgtggc ggcctctgtg cagtcgccgg ttccggagga gggcccaacc cggctgggtg     60 

ggtgggaagt gtggctggta acctggcagc cgcggagaga gagaagatta taaatggcag    120 

agccatttaa ctgtggttag ctgttggatt ctgatacttt cttaaaaata cgttcttgca    180 

ccaacatctt cattgggaac agttcagaaa aagcaaagag gagagccaac attcacattt    240 

accatggcta taccaataac agtgcttgac tgtgacctct tgctatatgg ccgtggtcac    300 

cggacattgg accgttttaa gctggatgat gtgactgatg aatacttgat gtccatgtat    360 

gggtttccac ggcagttcat ttattacttg gtggagctct tgggggcgaa tctttctagg    420 

cctactcagc gatccagggc tattagccca gagacacagg tccttgcagc attgggtttt    480 

tatacctcag gttccttcca gactcggatg ggagatgcca ttggaatcag tcaggcgtct    540 

atgagtcgtt gtgttgccaa tgtcactgaa gcacttgtgg aaagggcctc acagttcatt    600 

cgctttccag ctgatgaagc ctccattcag gctctgaagg atgaattcta tgggttggca    660 

gggatgccag gggtgatggg ggtggttgac tgtatccatg tggccatcaa ggcaccaaat    720 

gctgaagacc tctcctatgt gaaccgaaaa ggcctgcatt ctttaaactg cctgatggtg    780 

tgtgacatta gagggacact aatgaccgtg gagacaaact ggcccggcag cctacaggac    840 

tgtgctgtgc tgcagcagtc ttccctcagt agtcagtttg aagcgggtat gcacaaagat    900 

agctggcttc tgggtgacag ttccttcttt cttcgaacct ggctcatgac cccacttcac    960 

attcctgaaa ctccagcaga atatcgctat aacatggccc attctgcaac tcacagtgtg   1020 

attgagaaga ctttccgaac cctctgctcc cgattccgct gcctggatgg atccaagggg   1080 

gcactgcagt actcaccaga gaaatccagc catatcatct tggcctgttg tgtcctccac   1140 

aacatctccc tggagcatgg gatggatgtt tggtcctctc caatgacagg acccatggaa   1200 

cagcccccgg aagaggagta tgagcacatg gagtccctgg acttagaggc tgaccgtatt   1260 

cgtcaggagc taatgctcac tcattttagc taatgtagaa ggtggagagg agggatactt   1320 

cccaggagtt gtgacagact ttcctcctca tcacctttta cacagttcca tcatctagca   1380 

tgactgagta tacagatact tgtcataaac tgacatttaa tatgtgtgtt ttggtaaggt   1440 

tggggctatg ccagaatatc ttgattcatt tgcatatgca ttaattaaac tgaaaccaag   1500 

acagcggctc cctactatcc agtgaactct aggttgagta ccactaattt gaaagctcag   1560 

tggttgcaaa catttatgac tgtgcctaca aagtcatagt aaaggtcagg agttcaagac   1620 

aagaccagcc tggccaacat ggtgaaaccc cgtctctact aaaaatacaa aaattagcgg   1680 

ccgggtgcgg tggctcacgc ctgtaatccc agcactttgg gaggccgagg cgggcggatc   1740 

acctgagttc aggagttaag accagcctgg gcaacatggc aagaccctgt ctctactaaa   1800 

aatacaaaaa aattagctgg gcgtggtgac aggtgcctgt aatcccagct actcggtagg   1860 

ctgaggcagg agaatcactt gaaccaggga ggcggaggtt gtggtgagcc gagatcgtgc   1920 

cattgcactc cagactaggc gagaagagcg aaagtccgtc tcacaagaaa gatcagaaag   1980 

aaaataagcg gggcgggggg gcacatgccg gaaaacccga gaaccgggga ggcggcgcgg   2040 

ggacaaccgt ggaccctgcg acccgaggtt gcctgaccga atcatcgcat gggcccagct   2100 

ggtggcaagc aggttctccg aaaacaatat cacgagaaac aggggggcgg aaaaggacgt   2160 

cacacgataa acgccggccc aggggggcga aat                                2193 
 
           
             18  
             2926  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 3054202CB1  
             
           
            18 

gtctccatca agagcttctt ccagccctgg ctgggggaca caggttctga catgaagtaa     60 

attttgcaga agtcgtgttc ctgcgataag atacaaagat gtgaccttcc agttgtgtaa    120 

agctcttaaa ggctgtttag tatatcaagt gtgctaaaga acctggagct aaatggacta    180 

attctgagag agagggattt aactattcta gcaaagggat tgaataaatc ggcttctttg    240 

gtgcacctgt ctcttgcaaa ttgtccaatt ggagatggag gtttagaaat tatttgtcaa    300 

ggtataaaga gctctatcac tcttaagaca gtcaacttca caggatgtaa tctgacatgg    360 

cagggagcag atcacatggc caagatctta aagtatcaga ccatgagaag gcatgaagaa    420 

acctgggctg agagtcttcg ctataggaga cctgatcttg actgtatggc tggcttaaga    480 

cgtatcacac tgaattgcaa cacacttatt ggtgacctag gtgcatgtgc ttttgcagac    540 

tctctcagtg aggatttatg gctgagagct cttgacctgc aacagtgcgg cctcaccaat    600 

gaaggagcaa aggctttgct agaggccctt gaaaccaata caactctggt cgttctggat    660 

ataagaaaaa atccactcat tgatcattct atgatgaaag cagttatcaa aaaagtcctc    720 

cagaatggaa ggagtgccaa atcagagtac cagtggataa cttctccatc agtgaaggaa    780 

ccatccaaaa ctgctaaaca gaaaaggaga actataattc taggaagtgg tcacaaagga    840 

aaagctacta ttagaattgg attggctaca aagaaacctg taagtagtgg cagaaaacac    900 

tcccttggta aagaatatta tgcgcccgca cctcttccac ctggtgtgtc tggtttcttg    960 

ccgtggcgta ctgcagaacg tgcaaaaaga cacaggggtt tcccattaat caaaacacgt   1020 

gatatatgta atcagttgca gcaaccaggt tttcctgtga ctgtgacagt agagagtcct   1080 

tcatcctctg aagttgaaga ggttgatgat tcttcagaga gtgttcatga agtgcctgag   1140 

aaaactagta tagaacaaga agcattacag gaaaaactgg aggagtgcct aaagcagtta   1200 

aaggaagaaa gagtgataag gcttaaggtt gataaacgag tcagtgagct ggaacatgaa   1260 

aatgcccagt taagaaatat aaatttctct ttgtctgaag cccttcatgc acagtcattg   1320 

acaaatatga tcctggatga tgaaggtgtt ttgggcagca ttgagaattc ttttcagaag   1380 

tttcatgctt tcttggatct ccttaaagat gctgggcttg ggcagcttgc cacaatggct   1440 

gggatagatc agtcagattt tcaattacta ggtcatcccc agatgacttc tactgttagt   1500 

aatccaccta aagaagaaaa gaaggcgctt gaagatgaaa aaccagaacc gaagcagaat   1560 

gccctagggc aaatgcaaaa tatccaggtt tctatttgta tgcagtcagc ttacaatgaa   1620 

ggaacactaa tgaagtttca gaaaattaca ggtgatgcta gaattccttt gcctctcgac   1680 

tcctttcctg tcccagtttc tactccagag ggcttaggaa cttccagcaa caacctagga   1740 

gtcccagcta ctgagcagcg gcaggagtct tttgaaggat tcattgctag aatgtgttct   1800 

ccttcaccag atgcgacttc tggaactgga agtcaaagaa aagaagagga gttgtccaga   1860 

aatagcagat cttcttcaga gaaaaagacc aaaacagaat cccattgaaa tgactggaga   1920 

aatattaaaa taaaaataat agcagagttg gaaaaccaga aatttgaaca gtgaaatttc   1980 

tggaagataa gaagcagatg atttaagtac cagttaatta aaggatggaa cagctaagcc   2040 

attccactca tctttggagc atctgattct ggagtttgcc accaggctaa gaaagcagct   2100 

atctgaagtg ggagctctga cccaagaaat gctgggatcg gagaataagg gaattatcca   2160 

aaatggctcc gaagaggaac tgaagttaag ctgcccacat gatctctcta actatgatga   2220 

cctgccactt ccgtttataa tcaccatata agtgcctgta atcatttgtg ttcattaaaa   2280 

gtgaaccaga attcccattt ggatgaaaaa ataacacttc caactttaat cttaggccct   2340 

catttataaa tatggacaac caagaatcat caaatttgaa gaaaaccagt aacataaaag   2400 

gaggcatgaa attaaaatta acctgttcaa gaagatagtt actaggagaa acatgaaatt   2460 

tttaaattaa tgaatcaaaa tcttcagcaa ttcataaaga tactgtgttc ataaagaata   2520 

ggatgccatg aaaaaaatat ttagagtttc tggaaattaa aaatttgatt atgaaactga   2580 

aacactcaga agatggacta cacagcagaa tggattcatt tgaagcttaa attcatgaaa   2640 

tggaaggtat taattggtct tagacgtttc atcagcaact taattactta gaaaaaatct   2700 

ttctcagagt aactaagcaa aatgaacaat gaacccatta acgtgtggtt ttgttttttg   2760 

ggtttttttt ttttgagtca aggtctcact catgtcaccc aggctggggt gtagtgatgg   2820 

gatcacagct tattgtaacc atgaaccatt gggcttaaat tatcttccca cctcagcctc   2880 

ccaagtagct gcaatgtacc accatgccga agttttaaaa aattag                  2926 

 
           
             19  
             279  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5316792CB1  
             
           
            19 

atgagaatga gccatgcagg ttgcccagag agagcatcca ggcagaggga gcagaaagtt     60 

ccatcctcac ccagctctgc cggcccaggt actttctcct ctgccttcta ctcccagtct    120 

cactgcagtg caacacactt cagttttctg ggaactcctg atggaaagtg gctgtatttg    180 

ttcatcccta tagccttggg gcacagccag cagcccagac gacatgaggc tcccagccgg    240 

ccctgcctca cctctgcgcc ggtggcccat ccatgatga                           279 

 
           
             20  
             2131  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 5572967CB1  
             
           
            20 

tggagacgcc gccggccgcc gctggcgcat ggcgggtagg agctgtggcg cggggccttc     60 

caggagtctg agctatgagt ggcccctgtg gagagaagcc tgtcctggaa gccagcccca    120 

ccatgagtct gtgggaattt gaggacagcc acagccgtca gggcacccca aggccgggtc    180 

aagagctggc cgctgaggag gcctcggccc tggaactgca gatgaaggtg gacttcttcc    240 

ggaagctggg ctattcatcc acggagatcc acagcgtcct gcagaagctg ggcgtccagg    300 

cagacaccaa cacggtgctg ggtgagctgg tgaaacacgg gacagccacc gagcgggagc    360 

gccagacctc accggacccc tgccctcagc tccctctagt cccgcggggt ggtggcaccc    420 

ctaaggctcc caacctggag cctccactcc cagaagagga aaaggagggc agcgacctga    480 

gaccagtggt catcgatggg agcaacgtgg ccatgagcca tgggaacaag gaggtcttct    540 

cctgccgggg catcctgctg gcagtgaact ggtttctgga gcggggccac acagacatca    600 

cagtgtttgt gccatcctgg aggaaggagc agcctcggcc cgacgtgccc atcacagacc    660 

agcacatcct gcgggaactg gagaagaaga agatcctggt gttcacacca tcacgacgcg    720 

tgggtggcaa gcgggtggtg tgctatgacg acagattcat tgtgaagctg gcctacgagt    780 

ctgacgggat cgtggtttcc aacgacacat accgtgacct ccaaggcgag cggcaggagt    840 

ggaagcgctt catcgaggag cggctgctca tgtactcctt cgtcaatgac aagtttatgc    900 

cccctgatga cccactgggc cggcacgggc ccagcctgga caacttcctg cgtaagaagc    960 

cactcacttt ggagcacagg aagcagccgt gtccctatgg aaggaaatgc acctatggga   1020 

tcaagtgccg attcttccac ccagagcggc caagctgccc ccagcgctct gtggcagatg   1080 

agctccgtgc caatgctctc ctctcacccc ccagagcccc aagcaaggac aaaaatggcc   1140 

ggcggccttc accttcatcc cagtccagct ctctgctaac agagagtgag cagtgcagcc   1200 

tggatgggaa gaagctgggg gcccaggcat ccccagggtc ccgccaagag ggtctaacac   1260 

agacctatgc cccatcaggc aggagcctcg cacctagcgg gggcagtggc agcagctttg   1320 

ggcccacaga ctggctccca cagacgctgg actcactccc gtacgtctcc caggattgcc   1380 

tggactcggg cattggctcc ctggagagcc agatgtcgga actttggggg gttcgaggag   1440 

gaggccctgg tgagccgggc ccaccccgag ccccttacac gggctacagt ccctatggat   1500 

ctgagctccc agccaccgca gccttctctg cctttggccg ggccatgggt gctggccact   1560 

tcagtgtccc tgccgactac ccacccgcgc cccctgcctt tccacctcga gagtactggt   1620 

ctgaaccata cccactgccc ccacccacat cagtccttca ggagccccca gtgcagagcc   1680 

caggggctgg caggagcccg tggggcaggg caggcagcct ggccaaggag caggccagcg   1740 

tgtatactaa gctgtgtggt gtgtttcccc cgcacctggt ggaggctgtg atggggcgct   1800 

tcccacagct cctggacccc cagcagctgg ctgccgagat cctctcctac aagtcccagc   1860 

accccagtga gtaagctgcc tgtggctggc aagggcagca cccccagcct ccaagggccg   1920 

tcaggctggg ctttgggcca ttgagcagcc cattcccagc cctgaggccc accccagagg   1980 

ctggacagag ggaggattca agtcgggaag gaaacccaca aaccaaagat actgtaggat   2040 

tggttctggc ccatgcagca cctctagctg tctgcctcag tgggtcagaa gcgatcaccc   2100 

tgttgataca cattgtatct ctgtagttta a                                  2131 

 
           
             21  
             880  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7473247CB1  
             
           
            21 

gcggtccctc ccggcccggc ggaacgcgtc cttttaaggg ggcggggacc tgggggtctg     60 

gggccagcgc gcgggaggga cgcctgagtg cctcgagggc gccgttcggg cggggaggat    120 

cccgcgggtc ccactgaccc acgcggggtg gggccagggg tggacgctcg cccgtacgcg    180 

gtcgctactg atcatgcttg ggccagggtc caatcgcagg cgccccacgc agggggagcg    240 

aggcccaggg tcccccggag agcccatgga gaagtaccag gttttgtacc agctgaatcc    300 

tggggccttg ggggtgaacc tggtggtgga ggaaatggaa accaaagtca agcatgtgat    360 

aaagcaggtg gaatgcatgg atgaccatta cgccagtcag gccctggagg agggcacaga    420 

agccatgcat ctgcggaagt ccctccgcca gagcccaggc agcctgaagg ccgtcctgaa    480 

gacaatggag gagaagcaga tcccggatgt ggaaaccttc aggaatcttc tgcccttgat    540 

gctccagatc gacccctcgg atcgaataac gataaagtga gctcagggtc ggggtttatt    600 

ttaacctgtg gatttatctt tcaacatctc tccaccctaa tacaagcaca gctagttggc    660 

tttgtaacgc ctcaaagaac tccatcacag atgccctgat tatccctgca cagctaggct    720 

ttgcccagtt ctggctctcc caaaccgtgc tgcggcgagt aatcccgaat gtacggtgga    780 

gtgagcagac tgacccccag gaggcacagg aggcgtagcc cccaggaccc acgacacttt    840 

tagggttcca gaaaaaagtt ttcattctac ataaaaaaaa                          880 

 
           
             22  
             3787  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 7482930CB1  
             
           
            22 

ggagagatat gaccacaggc tcatgtgaaa catctccctc cagaattcag catctttcta     60 

gaccatatct cttctttgga ttattttaca aaaccagact accagcttct tacatccgtg    120 

tttgacaata gcatcaagac ttttggagta attgagagtg acccttttga ctgggagaag    180 

actggaaatg atggctccct aacaaccacc actacttcta ccacccctca gttgcacact    240 

cgcttgaccc ctgctgcaat tggaattgcc aatgctactc ccatccctgg agacttgctt    300 

cgagaaaata cagatgaggt atttccagat gaacagctta gcgatggaga aaatggcatc    360 

cctgttggtg tgtcaccaga taaattgcct ggatctctgg gacacccccg tccccaggag    420 

aaggatgttt gggaagagat ggatgccaac aaaaacaaga taaagcttgg aatttgtaag    480 

gctgctactg aagaggagaa cagccatggc caggcaaatg gtcttctcaa tgctccaagc    540 

cttgggtcac caattcgtgt ccgctcagag attactcagc cagacagaga tattccactg    600 

gtgcgaaagt tacgttccat tcacagcttt gagctggaaa aacgtctgac cctggagcca    660 

aagccagaca ctgacaagtt ccttgagacc tgcctggaga aaatgcagaa agataccagt    720 

gcaggaaaag aatctattct ccctgctctg ctgcataagc cttgcgttcc tgctgtgtcc    780 

cgtactgacc acatctggca ctatgatgaa gaatatcttc cagatgcctc caagcctgct    840 

tctgccaaca cccctgagca ggcagatggt ggtggcagca atggatttat agctgttaac    900 

ctgagctctt gcaagcaaga aattgattcc aaagaatggg tgattgtgga caaggagcag    960 

gaccttcagg attttaggac aaatgaggct gtaggacata aaacaactgg aagtccttct   1020 

gatgaggagc ctgaagtact tcaagtcctg gaggcatcac ctcaagatga aaagctccag   1080 

ttaggtcctt gggcagaaaa tgatcattta aagaaggaaa cctcaggtgt ggtcttagca   1140 

ctttctgcag agggtcctcc tactgctgct tcagaacaat atacagatag gctggaactc   1200 

cagcctggag ctgctagtca gtttattgca gcgacgccca caagtctaat ggaggcgcag   1260 

gcagaaggac cccttacagc gattacaatt cctagacctt ctgtggcatc tacacagtca   1320 

acttcaggaa gctttcactg tggtcagcag ccagagaaga aagatcttca gcccatggag   1380 

cccactgtgg aactttactc tccaagggaa aacttctctg gcttggttgt gacagagggt   1440 

gaacctccta gtggaggaag cagaacagat ttggggcttc agatagatca cattggtcat   1500 

gacatgttac ccaacattag agaaagtaac aaatctcaag acctgggacc aaaagaactt   1560 

cctgatcata atagactggt tgtgagagaa tttgaaaatc tccctgggga aactgaagag   1620 

aaaagcatcc ttttagagtc agataatgaa gatgagaagt taagtcgagg gcagcattgt   1680 

attgagatct cctctctccc aggagatttg gtaattgtgg aaaaggatca ctcagctact   1740 

actgaacctc ttgatgtgac aaaaacacag acttttagtg tggtgccaaa tcaagacaaa   1800 

aataatgaga taatgaagct tctgacagtt ggaacttcag aaatttcttc cagagacatt   1860 

gacccacatg ttgaaggtca gataggccaa gtggcagaaa tgcaaaaaaa taagatatct   1920 

aaggatgatg acatcatgag tgaagacttg ccaggtcatc aaggagacct ctctactttt   1980 

ttgcaccaag agggcaagag agagaaaatc acccctagaa atggagaact atttcattgt   2040 

gtttcagaga atgaacatgg tgccccaacc cggaaggata tggttaggtc atcctttgta   2100 

actagacaca gccgaatccc tgttttagca caagagatag actcaacttt ggaatcatcc   2160 

tctccagttt ctgcaaaaga aaagctcctc caaaagaaag cctatcagcc agacctagtc   2220 

aagcttctgg tggaaaaaag acaattcaag tccttccttg gcgacctctc aagtgcctct   2280 

gataaattgc tagaggagaa actagctact gttcctgctc ccttttgtga ggaggaagtg   2340 

ctcactccct tttcaagact gacagtagat tctcacctga gtaggtcagc tgaagatagc   2400 

tttctgtcac ccatcatctc ccagtctaga aagagcaaaa ttccaaggcc agtttcatgg   2460 

gtcaacacag atcaggtcaa tagctcaact tcgtctcagt tctttcctcg gccaccacca   2520 

ggaaagccac ccacgaggcc tggagtagaa gccaggctac gcagatataa agtcctaggg   2580 

agtagtaact ccgactcaga ccttttctcc cgcctggccc aaattcttca aaatggatct   2640 

cagaaacccc ggagcactac tcagtgcaag agtccaggat ctcctcacaa tccaaaaaca   2700 

ccacccaaga gtccagttgt ccctcgcagg agtcccagtg cctctcctcg aagctcatcc   2760 

ttgcctcgca cgtctagttc ctcaccatct agggctggac ggccccacca tgaccagagg   2820 

agttcgtccc cacatctggg gagaagcaag tcacctccca gccactcagg atcttcctcc   2880 

tccaggaggt cctgccaaca ggagcattgc aaacccagca agaatggcct gaaaggatcc   2940 

ggcagcctcc accaccactc agccagcact aaaacccccc aagggaagag taagccagcc   3000 

agtaaactca gcagatagga gccaggctgc atctctttga aaggtgtgag atcttcctcc   3060 

taaacctgat gcatgtgtgt ccctgtactt tctatgtaaa aaaatcagtg ttgatcttct   3120 

cttgcaaaag aaagtaacat gatcaattat ttataagaag acataataca tgataaggaa   3180 

ttacctaagg caggcagcaa gtagattagg aatcaatgtc tttgtacaag aaggaaaaat   3240 

agagcaaaaa tccaaggggg agaaactcat taaaatgagc tctcattttt taagctgcct   3300 

ttgaaacaaa agagttgagg ataggagata gaatggaatt ttaggggggt tgcctaattt   3360 

ttttaagcct caattcaaag attatatagc aaaagtgaaa cttcttgttt gatattttca   3420 

ttcaaaactt tcccaccctg aagagtcatt gatcagatat tagattatat aagaagtctg   3480 

ttgccaggga gccagtattc atgtatattt ggcttgtgtg tttatttcgt gtattgagaa   3540 

tgaacacctt tacttagcct cattcctagt aacctccctg gagttcagat tttatagtta   3600 

aaaattagaa tgtctcgtct gattcaatct ctctgcttaa attaaatggt cctaggttgt   3660 

ctatcaaatc caattatttt ttataaggtc ccctgatttt tatatcaaga gcagagtttt   3720 

aaatattact tttcatttga cactcaacag tgggcgaaga attgaaataa gtttgatacg   3780 

gcactag                                                             3787 

 
           
             23  
             2130  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2049942CB1  
             
           
            23 

ttttttttaa gtgttagatg tttttgatat tttaaaaaag catctaggct gcttgtggaa     60 

gtcagaccaa aatagcagga aggtattgca gcaagatgga tttgggaaag gaccaatctc    120 

atttgaagca ccatcagaca cctgaccctc atcaagaaga gaaccattct ccagaagtca    180 

ttggaacctg gagtttgaga aacagagaac tacttagaaa aagaaaagct gaagtgcatg    240 

aaaaggaaac atcacaatgg ctatttggag aacagaaaaa acgcaagcag cagagaacag    300 

gaaaaggaaa tcgaagaggc agaaagagac aacaaaacac agaattgaag gtggagcctc    360 

agccacagat agaaaaggaa atagtggaga aagcactggc acctatagag aaaaaaactg    420 

agccacctgg gagcataacc aaagtatttc cttcagtagc ctccccgcaa aaagttgtgc    480 

ctgaggaaca cttttctgaa atatgtcaag aaagtaacat atatcaggag aatttttctg    540 

agtaccaaga aatagcagta caaaaccatt cttctgaaac atgccaacat gtgtctgaac    600 

ctgaagacct ctctcctaaa atgtaccaag aaatatctgt acttcaagac aattcttcca    660 

aaatatgcca agacatgaag gaacctgaag acaactctcc taacacatgc caagtaatat    720 

ctgtaattca agaccatcct ttcaaaatgt accaagatat ggctaaacga gaagatctgg    780 

ctcctaaaat gtgccaagaa gctgctgtac ccaaaatcct tccttgtcca acatctgaag    840 

acacagctga tctggcagga tgctctcttc aagcatatcc aaaaccagat gtgcctaaag    900 

gctatattct tgacacagac caaaatccag cagaaccaga ggaatacaat gaaacagatc    960 

aaggaatagc tgagacagaa ggcctttttc ctaaaataca agaaatagct gagcctaaag   1020 

acctttctac aaaaacacac caagaatcag ctgaacctaa ataccttcct cataaaacat   1080 

gtaacgaaat tattgtgcct aaagccccct ctcataaaac aatccaagaa acacctcatt   1140 

ctgaagacta ttcaattgaa ataaaccaag aaactcctgg gtctgaaaaa tattcacctg   1200 

aaacgtatca agaaatacct gggcttgaag aatattcacc tgaaatatac caagaaacat   1260 

cccagcttga agaatattca cctgaaatat accaagaaac accggggcct gaagacctct   1320 

ctactgagac atataaaaat aaggatgtgc ctaaagaatg ctttccagaa ccacaccaag   1380 

aaacaggtgg gccccaaggc caggatccta aagcacacca ggaagatgct aaagatgctt   1440 

atacttttcc tcaagaaatg aaagaaaaac ccaaagaaga gccaggaata ccagcaattc   1500 

tgaatgagag tcatccagaa aatgatgtct atagttatgt tttgttttaa caatgctcaa   1560 

ccataaagtt gtggtccaat ggaacataca gcttaatagt ttatgcgtga ttttctcaaa   1620 

atattgtaaa acttttgaca atgctcatta atattatttt ttctatttgt agaccatatc   1680 

tgaaagaaat aacatttttt aaggctctac cacatagaca atatcatgct agaatgtgtg   1740 

tgtgtgtgtg tgtgtgtgtg tgtatgtatg tataggtcgg ggagaggata gtggtgggaa   1800 

cagacaaata aggaagcggg gaggactgga taattggttt tcccccctaa gaacatttat   1860 

ttacgtctta agagcagata agtgactaag actgaacaca tacattttgt ggagtatata   1920 

gttttcttgt aaatgctgtt caattattaa tgtaacagta gcatcaaaat tttattcagg   1980 

ctttagttga ctcttttggt cagttttaac aattctcctt aaaagatatt ttggagtgat   2040 

gaatgtagtt tacttttgta tttgaatttt gattttctat ttttattttt taaatattgt   2100 

atttgtgcac aatgtacatt aaatcattat                                    2130 

 
           
             24  
             2607  
             DNA  
             Homo sapiens  
             
               misc_feature  
               Incyte ID No 2418711CB1  
             
           
            24 

ggcagcatca acgccggcgg ctgcaacttc aactccttcc tgcggcgtac ggtgcggttt     60 

gtgggtgagt tgcgggccgc gccccgaccc tgagctacct ccacatgcag ggggtggggc    120 

tgtcccgggt ccccagctcc ccgcctggcc gagccttccg ccccgcaggt gtccacgtgt    180 

tcggcctgtg tgccacagcc ctggtgacgg acgtgatcca gctggccacg ggttaccaca    240 

ctcccttctt cctcaccgtc tgcaagccca actacactct cctgggcacg tcctgcgagg    300 

tcaaccccta catcacgcag gacatctgct ccggccacga catccacgcc atcctgtctg    360 

cacggaagac cttcccgtcc cagcacgcca cgctgtcagc cttcgccgcg gtctatgtgt    420 

cgatgtactt caactcggtc atctcggaca ccaccaagct gctgaagccc atcctggtct    480 

tcgcctttgc catcgccgcg ggcgtatgcg ggctcacgca gatcacgcag taccgcagcc    540 

accctgtgga cgtgtatgcc ggcttcctca tcggggcggg catcgctgcc tacctggcct    600 

gccacgcggt gggcaacttc caggccccac ctgcagagaa gcccgcggcc ccggcccccg    660 

ccaaggacgc gctgcgggcc ctgacgcagc ggggccacga ctcggtttat cagcagaata    720 

agtcggtgag caccgacgag ctggggcccc cagggcggct ggagggcgcg ccccggcccg    780 

tggcccgcga gaagacctcg ctgggcagcc tgaagcgcgc cagcgtggac gtggacctgc    840 

tggccccgcg cagccccatg gccaaggaga acatggtgac cttcagccac acgctgccca    900 

gggccagcgc gccctcgctg gacgaccccg cgcgccgcca catgaccatc cacgtgccgc    960 

tggacgcctc gcgctccaag cagctcatca gcgagtggaa gcagaagagc ctggagggcc   1020 

cgcggcctgg ggctgcccga cgacgccagc cccgggcacc tgcgcgcgcc cgccgaaccc   1080 

atggcggagg aggaggaaga ggaggaggac gaagaggaag aggaggagga ggaagaggag   1140 

gaggacgagg gcccggcccc gccctcgctc taccccaccg tgcaggcgcg gccggggctg   1200 

gggcctcggg tcatcctccc accgcgcgcg gggccgccgc cgctggtgca catcccggag   1260 

gagggcgcgc aggcgggggc cggcctgtcc cccaaaagcg gcgccggggt gcgcgccaag   1320 

tggctcatga tggccgagaa gagcggggcg gcagtggcca accctccgcg gctgctgcag   1380 

gtcatcgcca tgtccaaggc tccgggcgcg ccgggcccca aggcggccga gacggcgtcg   1440 

tcgtccagcg ccagctccga ctcctcgcag taccggtcgc cgtcggaccg cgactccgcc   1500 

agcatcgtga ccatcgacgc gcacgcgccg caccaccccg tggtgcacct gtcggccggc   1560 

ggcgcgccct gggagtggaa ggcggcgggc ggcggggcca aggcggaggc cgacggcggc   1620 

tacgagctgg gggacctggc gcgcggcttc cgcggcgggg ccaagccccc gggcgtgtcc   1680 

cccggctcgt cggtcagcga cgtggaccag gaggagccgc ggttcggggc cgtggccacc   1740 

gtcaacctgg ccacgggcga ggggctgccc ccgctgggcg cggccgatgg ggcgctgggc   1800 

ccgggcagcc gggagtccac gctgcggcgc cacgcgggcg gcctggggct ggcggagcgc   1860 

gaggcggagg cggaggccga gggctacttc cgcaagatgc aggcgcgccg cttccccgac   1920 

tagcgcggcg gggccggggg cgggcggggg gcgggccgag ggcgcgggcg gccgcgcgga   1980 

tgctcaataa agcggcataa accgaggtcc ggctcttggt cattcgctct ggcccgcacg   2040 

ccccacgcag ggacccccac tctcagggcc gggcccaccc cgcccgtggc cccacctggc   2100 

gcttcggcgg acacccgggc gggagtcggg gccgcccgcg gcacagaaag aggaagccag   2160 

caacgaaggc ggaacggagc gaggatacag aagatttatt cgaagtccag gtacagactg   2220 

gccaacctgc ctctacagcg tccacagcga acacagggct agacaaggga ggagtttctc   2280 

aaacggtttt aatcggttct ctccgcgtca caagccatcg ggtaaggcaa cggaatgtgc   2340 

gtggggtccc ctgtggctcc gcggtcacaa tactgagcct ggaattgctg ttagcaaaat   2400 

atacatttgt gtcaccataa aaaaccgcgc cgccgcccct cgggtctcac aacaggtata   2460 

aaaaattata aatatttaca cccttgttac acgcttttac ggaaagggga tcctaggaga   2520 

gcccccggga caggacgcgg gggcggtaga aagagcacag agaagacagg aggagcgccc   2580 

gccttccggg tcccagcatc agaggca                                       2607