NOVEL COMPOUNDS

Abstract: Polypeptides and polynucleotides of the genes set forth in Table I and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing polypeptides and polynucleotides of the genes set forth in Table I in diagnostic assays.

Description: Novel Compounds Field of Invention This invention relates to newly identified polypeptides and polynucleotides encoding such polypeptides, to their use in diagnosis and in identifying compounds that may be agonists, antagonists that are potentially useful in therapy, and to production of such polypeptides and polynucleotides. The polynucleotides and polypeptides of the present invention also relate to proteins with signal sequences which allow them to be secreted extracellularly or membrane-associated (hereinafter often referred collectively as secreted proteins or secreted polypeptides). Background of the Invention The drug discovery process is currently undergoing a fundamental revolution as it embraces "functional genomics", that is, high throughput genome- or gene-based biology. This approach as a means to identify genes and gene products as therapeutic targets is rapidly superseding earlier approaches based on "positional cloning". A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position. Functional genomics relies heavily on high-throughput DNA sequencing technologies and the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery. Proteins and polypeptides that are naturally secreted into blood, lymph and other body fluids, or secreted into the cellular membrane are of primary interest for pharmaceutical research and development. The reason for this interest is the relative ease to target protein therapeutics into their place of action (body fluids or the cellular membrane). The natural pathway for protein secretion into extracellular space is the endoplasmic reticulum in eukaryotes and the inner membrane in prokaryotes (Palade, 1975, Science, 189, 347; Milstein, Brownlee, Harrison, and Mathews, 1972, Nature New Biol, 239, 117; Blobel, and Dobberstein, 1975, J. Cell. Biol., 67, 835). On the other hand, there is no known natural pathway for exporting a protein from the exterior of the cells into the cytosol (with the exception of pinocytosis, a mechanism of snake venom toxin intrusion into cells). Therefore targeting protein therapeutics into cells poses extreme difficulties. The secreted and membrane-associated proteins include but are not limited to all peptide hormones and their receptors (including but not limited to insulin, growth hormones, chemokines, cytokines, neuropeptides, integrins, kallikreins, lamins, melanins, natriuretic hormones, neuropsin, neurotropins, pituitiary hormones, pleiotropins, prostaglandins, secretogranins, selectins, thromboglobulins, thymosins), the breast and colon cancer gene products, leptin, the obesity gene protein and its receptors, serum albumin, superoxide dismutase, spliceosome proteins, 7TM (transmembrane) proteins also called as G-protein coupled receptors, immunoglobulins, several families of serine proteinases (including but not limited to proteins of the blood coagulation cascade, digestive enzymes), deoxyribonuclease I, etc. Therapeutics based on secreted or membrane-associated proteins approved by FDA or foreign agencies include but are not limited to insulin, glucagon, growth hormone, chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone, calcitonin, adrenocorticotropic hormone (ACTH), vasopressin, interleukines, interferones, immunoglobulins, lactofeπϊn (diverse products marketed by several companies), tissue-type plasminogen activator (Alteplase by Genentech), hyaulorindase (Wydase by Wyeth-Ayerst), dornase alpha (Pulmozyme\ by Genentech), Chymodiactin (chymopapain by Knoll), alglucerase (Ceredase by Genzyme), streptokinase (Kabikinase by Pharmacia) (Streptase by Astra), etc. This indicates that secreted and membrane-associated proteins have an established, proven history as therapeutic targets. Clearly, there is a need for identification and characterization of further secreted and membrane-associated proteins which can play a role in preventing, ameliorating or correcting dysfunction or disease, including but not limited to diabetes, breast- , prostate-, colon cancer and other malignant tumors, hyper- and hypotension, obesity, bulimia, anorexia, growth abnormalities, asthma, manic depression, dementia, delirium, mental retardation, Huntington's disease, Tourette's syndrome, schizophrenia, growth, mental or sexual development disorders, and dysfunctions of the blood cascade system including those leading to stroke. The proteins of the present invention which include the signal sequences are also useful to further elucidate the mechanism of protein transport which at present is not entirely understood, and thus can be used as research tools. Summary of the Invention The present invention relates to particular polypeptides and polynucleotides of the genes set forth in Table I, including recombinant materials and methods for their production. Such polypeptides and polynucleotides are of interest in relation to methods of treatment of certain diseases, including, but not limited to, the diseases set forth in Tables III and V, hereinafter referred to as "diseases of the invention". In a further aspect, the invention relates to methods for identifying agonists and antagonists (e.g., inhibitors) using the materials provided by the invention, and treating conditions associated with imbalance of polypeptides and/or polynucleotides of the genes set forth in Table I with the identified compounds. In still a further aspect, the invention relates to diagnostic assays for detecting diseases associated with inappropriate activity or levels the genes set forth in Table I. Another aspect ofthe invention concerns a polynucleotide comprising any of the nucleotide sequences set forth in the Sequence Listing and a polypeptide comprising a polypeptide encoded by the nucleotide sequence. In another aspect, the invention relates to a polypeptide comprising any of the polypeptide sequences set forth in the Sequence Listing and recombinant materials and methods for their production. Another aspect ofthe invention relates to methods for using such polypeptides and polynucleotides. Such uses include the treatment of diseases, abnormalities and disorders (hereinafter simply referred to as diseases) caused by abnormal expression, production, function and or metabolism of the genes of this invention, and such diseases are readily apparent by those skilled in the art from the homology to other proteins disclosed for each attached sequence. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with the imbalance with the identified compounds. Yet another aspect ofthe invention relates to diagnostic assays for detecting diseases associated with inappropriate activity or levels of the secreted proteins ofthe present invention. Description of the Invention In a first aspect, the present invention relates to polypeptides the genes set forth in Table I. Such polypeptides include: (a) an isolated polypeptide encoded by a polynucleotide comprising a sequence set forth in the Sequence Listing, herein when referring to polynucleotides or polypeptides of the Sequence Listing, a reference is also made to the Sequence Listing referred to in the Sequence Listing; (b) an isolated polypeptide comprising a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; (c) an isolated polypeptide comprising a polypeptide sequence set forth in the Sequence Listing; (d) an isolated polypeptide having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; (e) a polypeptide sequence set forth in the Sequence Listing; and (f) an isolated polypeptide having or comprising a polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence set forth in the Sequence Listing; (g) fragments and variants of such polypeptides in (a) to (f). Polypeptides of the present invention are believed to be members of the gene families set forth in Table II . They are therefore of therapeutic and diagnostic interest for the reasons set forth in Tables III and V. The biological properties of the polypeptides and polynucleotides of the genes set forth in Table I are hereinafter referred to as "the biological activity" of polypeptides and polynucleotides of the genes set forth in Table I. Preferably, a polypeptide of the present invention exhibits at least one biological activity of the genes set forth in Table I. Polypeptides of the present invention also include variants of the aforementioned polypeptides, including all allelic forms and splice variants. Such polypeptides vary from the reference polypeptide by insertions, deletions, and substitutions that may be conservative or non-conservative, or any combination thereof. Particularly preferred variants are those in which several, for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acids are inserted, substituted, or deleted, in any combination. Preferred fragments of polypeptides of the present invention include an isolated polypeptide comprising an amino acid sequence having at least 30, 50 or 100 contiguous amino acids from an amino acid sequence set forth in the Sequence Listing, or an isolated polypeptide comprising an amino acid sequence having at least 30, 50 or 100 contiguous amino acids truncated or deleted from an amino acid sequence set forth in the Sequence Listing. Preferred fragments are biologically active fragments that mediate the biological activity of polypeptides and polynucleotides of the genes set forth in Table I, including those with a similar activity or an improved activity, or with a decreased undesirable activity. Also preferred are those fragments that are antigenic or immunogenic in an animal, especially in a human. Fragments of a polypeptide of the invention may be employed for producing the corresponding full-length polypeptide by peptide synthesis; therefore, these variants may be employed as intermediates for producing the full-length polypeptides of the invention. A polypeptide of the present invention may be in the form of the "mature" protein or may be a part of a larger protein such as a precursor or a fusion protein. It is often advantageous to include an additional amino acid sequence that contains secretory or leader sequences, pro-sequences, sequences that aid in purification, for instance multiple histidine residues, or an additional sequence for stability during recombinant production. Polypeptides of the present invention can be prepared in any suitable manner, for instance by isolation form naturally occurring sources, from genetically engineered host cells comprising expression systems (vide infra) or by chemical synthesis, using for instance automated peptide synthesizers, or a combination of such methods. Means for preparing such polypeptides are well understood in the art. In a further aspect, the present invention relates to polynucleotides of the genes set forth in Table I. Such polynucleotides include: (a) an isolated polynucleotide comprising a polynucleotide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polynucleotide sequence set forth in the Sequence Listing; (b) an isolated polynucleotide comprising a polynucleotide set forth in the Sequence Listing; (c) an isolated polynucleotide having at least 95%, 96%, 97%, 98%, or 99% identity to a polynucleotide set forth in the Sequence Listing; (d) an isolated polynucleotide set forth in the Sequence Listing; (e) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; (f) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing; (g) an isolated polynucleotide having a polynucleotide sequence encoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptide sequence set forth in the Sequence Listing; (h) an isolated polynucleotide encoding a polypeptide set forth in the Sequence Listing; (i) an isolated polynucleotide having or comprising a polynucleotide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polynucleotide sequence set forth in the Sequence Listing; (j) an isolated polynucleotide having or comprising a polynucleotide sequence encoding a polypeptide sequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to a polypeptide sequence set forth in the Sequence Listing; and polynucleotides that are fragments and variants of the above mentioned polynucleotides or that are complementary to above mentioned polynucleotides, over the entire length thereof. Preferred fragments of polynucleotides of the present invention include an isolated polynucleotide comprising an nucleotide sequence having at least 15, 30, 50 or 100 contiguous nucleotides from a sequence set forth in the Sequence Listing, or an isolated polynucleotide comprising a sequence having at least 30, 50 or 100 contiguous nucleotides truncated or deleted from a sequence set forth in the Sequence Listing. Preferred variants of polynucleotides of the present invention include splice variants, allelic variants, and polymorphisms, including polynucleotides having one or more single nucleotide polymorphisms (SNPs). Polynucleotides of the present invention also include polynucleotides encoding polypeptide variants that comprise an amino acid sequence set forth in the Sequence Listing and in which several, for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acid residues are substituted, deleted or added, in any combination. In a further aspect, the present invention provides polynucleotides that are RNA transcripts of the DNA sequences of the present invention. Accordingly, there is provided an RNA polynucleotide that: (a) comprises an RNA transcript of the DNA sequence encoding a polypeptide set forth in the Sequence Listing; (b) is a RNA transcript of a DNA sequence encoding a polypeptide set forth in the Sequence Listing; (c) comprises an RNA transcript of a DNA sequence set forth in the Sequence Listing; or (d) is a RNA transcript of a DNA sequence set forth in the Sequence Listing; and RNA polynucleotides that are complementary thereto. The polynucleotide sequences set forth in the Sequence Listing show homology with the polynucleotide sequences set forth in Table II. A polynucleotide sequence set forth in the Sequence Listing is a cDNA sequence that encodes a polypeptide set forth in the Sequence Listing. A polynucleotide sequence encoding a polypeptide set forth in the Sequence Listing may be identical to a polypeptide encoding a sequence set forth in the Sequence Listing or it may be a sequence other than a sequence set forth in the Sequence Listing, which, as a result of the redundancy (degeneracy) of the genetic code, also encodes a polypeptide set forth in the Sequence Listing. A polypeptide of a sequence set forth in the Sequence Listingis related to other proteins of the gene families set forth in Table II, having homology and/or structural similarity with the polypeptides set forth in Table II. Preferred polypeptides and polynucleotides of the present invention are expected to have, inter alia, similar biological functions/properties to their homologous polypeptides and polynucleotides. Furthermore, preferred polypeptides and polynucleotides of the present invention have at least one activity of the genes set forth in Table I. Polynucleotides of the present invention may be obtained using standard cloning and screening techniques from a cDNA library derived from mRNA from the tissues set forth in Table IV (see for instance, Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)). Polynucleotides of the invention can also be obtained from natural sources such as genomic DNA libraries or can be synthesized using well known and commercially available techniques. When polynucleotides of the present invention are used for the recombinant production of polypeptides of the present invention, the polynucleotide may include the coding sequence for the mature polypeptide, by itself, or the coding sequence for the mature polypeptide in reading frame with other coding sequences, such as those encoding a leader or secretory sequence, a pre-, or pro- or prepro- protem sequence, or other fusion peptide portions. For example, a marker sequence that facilitates purification of the fused polypeptide can be encoded. In certain preferred embodiments of this aspect of the invention, the marker sequence is a hexa-histidine peptide, as provided in the pQE vector (Qiagen, Inc.) and described in Gentz et al, Proc Natl Acad Sci USA (1989) 86:821-824, or is an HA tag. A polynucleotide may also contain non-coding 5' and 3' sequences, such as transcribed, non-translated sequences, splicing and polyadenylation signals, ribosome binding sites and sequences that stabilize mRNA. Polynucleotides that are identical, or have sufficient identity to a polynucleotide sequence set forth in the Sequence Listing, may be used as hybridization probes for cDNA and genomic DNA or as primers for a nucleic acid amplification reaction (for instance, PCR). Such probes and primers may be used to isolate full-length cDNAs and genomic clones encoding polypeptides of the present invention and to isolate cDNA and genomic clones of other genes (including genes encoding paralogs from human sources and orthologs and paralogs from other species) that have a high sequence similarity to sequences set forth in the Sequence Listing, typically at least 95% identity. Preferred probes and primers will generally comprise at least 15 nucleotides, preferably, at least 30 nucleotides and may have at least 50, if not at least 100 nucleotides. Particularly preferred probes will have between 30 and 50 nucleotides. Particularly preferred primers will have between 20 and 25 nucleotides. A polynucleotide encoding a polypeptide of the present invention, including homologs from other species, may be obtained by a process comprising the steps of screening a library under stringent hybridization conditions with a labeled probe having a sequence set forth in the Sequence Listing or a fragment thereof, preferably of at least 15 nucleotides; and isolating full-length cDNA and genomic clones containing the polynucleotide sequence set forth in the Sequence Listing. Such hybridization techniques are well known to the skilled artisan. Preferred stringent hybridization conditions include overnight incubation at 42°C in a solution comprising: 50% formamide, 5xSSC (150mM NaCl, 15mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5x Denhardt's solution, 10 % dextran sulfate, and 20 microgram/ml denatured, sheared salmon sperm DNA; followed by washing the filters in O.lx SSC at about 65°C. Thus the present invention also includes isolated polynucleotides, preferably with a nucleotide sequence of at least 100, obtained by screening a library under stringent hybridization conditions with a labeled probe having the sequence set forth in the Sequence Listing or a fragment thereof, preferably of at least 15 nucleotides. The skilled artisan will appreciate that, in many cases, an isolated cDNA sequence will be incomplete, in that the region coding for the polypeptide does not extend all the way through to the 5' terminus. This is a consequence of reverse transcriptase, an enzyme with inherently low "processivity" (a measure of the ability of the enzyme to remain attached to the template during the polymerisation reaction), failing to complete a DNA copy of the mRNA template during first strand cDNA synthesis. There are several methods available and well known to those skilled in the art to obtain full-length cDNAs, or extend short cDNAs, for example those based on the method of Rapid Amplification of cDNA ends (RACE) (see, for example, Frohman et al., Proc Nat Acad Sci USA 85, 8998-9002, 1988). Recent modifications of the technique, exemplified by the Marathon (trade mark) technology (Clontech Laboratories Inc.) for example, have significantly simplified the search for longer cDNAs. In the Marathon (trade mark) technology, cDNAs have been prepared from mRNA extracted from a chosen tissue and an 'adaptor' sequence ligated onto each end. Nucleic acid amplification (PCR) is then carried out to amplify the "missing" 5' end of the cDNA using a combination of gene specific and adaptor specific oligonucleotide primers. The PCR reaction is then repeated using 'nested' primers, that is, primers designed to anneal within the amplified product (typically an adapter specific primer that anneals further 3 'in the adaptor sequence and a gene specific primer that anneals further 5' in the known gene sequence). The products of this reaction can then be analyzed by DNA sequencing and a full-length cDNA constructed either by joining the product directly to the existing cDNA to give a complete sequence, or carrying out a separate full-length PCR using the new sequence information for the design of the 5 'primer. Recombinant polypeptides of the present invention may be prepared by processes well known in the art from genetically engineered host cells comprising expression systems. Accordingly, in a further aspect, the present invention relates to expression systems comprising a polynucleotide or polynucleotides of the present invention, to host cells which are genetically engineered with such expression systems and to the production of polypeptides of the invention by recombinant techniques. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. For recombinant production, host cells can be genetically engineered to incorporate expression systems or portions thereof for polynucleotides of the present invention. Polynucleotides may be introduced into host cells by methods described in many standard laboratory manuals, such as Davis et al., Basic Methods in Molecular Biology (1986) and Sambrook et al.(ibid). Preferred methods of introducing polynucleotides into host cells include, for instance, calcium phosphate transfection, DEAE-dextran mediated transfection, transvection, micro-injection, cationic lipid- mediated transfection, electroporation, transduction, scrape loading, ballistic introduction or infection. Representative examples of appropriate hosts include bacterial cells, such as Streptococci, Staphylococci, E. coli, Streptomyces and Bacillus subtilis cells; fungal cells, such as yeast cells and Aspergillus cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, HeLa, C127, 3T3, BHK, HEK 293 and Bowes melanoma cells; and plant cells. A great variety of expression systems can be used, for instance, chromosomal, episomal and virus-derived systems, e.g., vectors derived from bacterial plasmids, from bacteriophage, from transposons, from yeast episomes, from insertion elements, from yeast chromosomal elements, from viruses such as baculoviruses, papova viruses, such as SV40, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabies viruses and retroviruses, and vectors derived from combinations thereof, such as those derived from plasmid and bacteriophage genetic elements, such as cosmids and phagemids. The expression systems may contain control regions that regulate as well as engender expression. Generally, any system or vector that is able to maintain, propagate or express a polynucleotide to produce a polypeptide in a host may be used. The appropriate polynucleotide sequence may be inserted into an expression system by any of a variety of well-known and routine techniques, such as, for example, those set forth in Sambrook et al., (ibid). Appropriate secretion signals may be incorporated into the desired polypeptide to allow secretion of the translated protein into the lumen of the endoplasmic reticulum, the periplasmic space or the extracellular environment. These signals may be endogenous to the polypeptide or they may be heterologous signals. If a polypeptide of the present invention is to be expressed for use in screening assays, it is generally preferred that the polypeptide be produced at the surface of the cell. In this event, the cells may be harvested prior to use in the screening assay. If the polypeptide is secreted into the medium, the medium can be recovered in order to recover and purify the polypeptide. If produced intracellularly, the cells must first be lysed before the polypeptide is recovered. Polypeptides of the present invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography is employed for purification. Well known techniques for refolding proteins may be employed to regenerate active conformation when the polypeptide is denatured during intracellular synthesis, isolation and/or purification. Polynucleotides of the present invention may be used as diagnostic reagents, through detecting mutations in the associated gene. Detection of a mutated form of a gene is characterized by the polynucleotides set forth in the Sequence Listing in the cDNA or genomic sequence and which is associated with a dysfunction. Will provide a diagnostic tool that can add to, or define, a diagnosis of a disease, or susceptibility to a disease, which results from under-expression, over-expression or altered spatial or temporal expression of the gene. Individuals carrying mutations in the gene may be detected at the DNA level by a variety of techniques well known in the art. Nucleic acids for diagnosis may be obtained from a subject's cells, such as from blood, urine, saliva, tissue biopsy or autopsy material. The genomic DNA may be used directly for detection or it may be amplified enzymatically by using PCR, preferably RT- PCR, or other amplification techniques prior to analysis. RNA or cDNA may also be used in similar fashion. Deletions and insertions can be detected by a change in size of the amplified product in comparison to the normal genotype. Point mutations can be identified by hybridizing amplified DNA to labeled nucleotide sequences of the genes set forth in Table I. Perfectly matched sequences can be distinguished from mismatched duplexes by RNase digestion or by differences in melting temperatures. DNA sequence difference may also be detected by alterations in the electrophoretic mobility of DNA fragments in gels, with or without denaturing agents, or by direct DNA sequencing (see, for instance, Myers et al, Science (1985) 230:1242). Sequence changes at specific locations may also be revealed by nuclease protection assays, such as RNase and SI protection or the chemical cleavage method (see Cotton et al., Proc Natl Acad Sci USA (1985) 85: 4397-4401). An array of oligonucleotides probes comprising polynucleotide sequences or fragments thereof of the genes set forth in Table I can be constructed to conduct efficient screening of e.g., genetic mutations. Such arrays are preferably high density arrays or grids. Array technology methods are well known and have general applicability and can be used to address a variety of questions in molecular genetics including gene expression, genetic linkage, and genetic variability, see, for example, M. Chee et al., Science, 274, 610-613 (1996) and other references cited therein. Detection of abnormally decreased or increased levels of polypeptide or mRNA expression may also be used for diagnosing or determining susceptibility of a subject to a disease of the invention. Decreased or increased expression can be measured at the RNA level using any of the methods well known in the art for the quantitation of polynucleotides, such as, for example, nucleic acid amplification, for instance PCR, RT- PCR, RNase protection, Northern blotting and other hybridization methods. Assay techniques that can be used to determine levels of a protein, such as a polypeptide of the present invention, in a sample derived from a host are well-known to those of skill in the art. Such assay methods include radio-immunoassays, competitive-binding assays, Western Blot analysis and ELISA assays. Thus in another aspect, the present invention relates to a diagnostic kit comprising: (a) a polynucleotide of the present invention, preferably the nucleotide sequence set forth in the Sequence Listing , or a fragment or an RNA transcript thereof; (b) a nucleotide sequence complementary to that of (a); (c) a polypeptide of the present invention, preferably the polypeptide set forth in the Sequence Listing or a fragment thereof; or (d) an antibody to a polypeptide of the present invention, preferably to the polypeptide set forth in the Sequence Listing . It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise a substantial component. Such a kit will be of use in diagnosing a disease or susceptibility to a disease, particularly diseases of the invention, amongst others. The polynucleotide sequences of the present invention are valuable for chromosome localisation studies. The sequences set forth in the Sequence Listing are specifically targeted to, and can hybridize with, a particular location on an individual human chromosome. The mapping of relevant sequences to chromosomes according to the present invention is an important first step in correlating those sequences with gene associated disease. Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found in, for example, V. McKusick, Mendelian Inheritance in Man (available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and diseases that have been mapped to the same chromosomal region are then identified through linkage analysis (co-inheritance of physically adjacent genes). Precise human chromosomal localisations for a genomic sequence (gene fragment etc.) can be determined using Radiation Hybrid (RH) Mapping (Walter, M. Spillett, D., Thomas, P., Weissenbach, J., and Goodfellow, P., (1994) A method for constructing radiation hybrid maps of whole genomes, Nature Genetics 7, 22- 28). A number of RH panels are available from Research Genetics (Huntsville, AL, USA) e.g. the GeneBridge4 RH panel (Hum Mol Genet 1996 Mar;5(3):339-46 A radiation hybrid map of the human genome. Gyapay G, Schmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D, Muselet D, PrudΗomme JF, Dib C, Auffray C, Morissette J, Weissenbach J, Goodfellow PN). To determine the chromosomal location of a gene using this panel, 93 PCRs are performed using primers designed from the gene of interest on RH DNAs. Each of these DNAs contains random human genomic fragments maintained in a hamster background (human / hamster hybrid cell lines). These PCRs result in 93 scores indicating the presence or absence of the PCR product of the gene of interest. These scores are compared with scores created using PCR products from genomic sequences of known location. This comparison is conducted at http://www.genome.wi.mit.edu/. The polynucleotide sequences of the present invention are also valuable tools for tissue expression studies. Such studies allow the determination of expression patterns of polynucleotides of the present invention which may give an indication as to the expression patterns of the encoded polypeptides in tissues, by detecting the mRNAs that encode them. The techniques used are well known in the art and include in situ hydridization techniques to clones arrayed on a grid, such as cDNA microarray hybridization (Schena et al, Science, 270, 467-470, 1995 and Shalon et al, Genome Res, 6, 639-645, 1996) and nucleotide amplification techniques such as PCR. A preferred method uses the TAQMAN (Trade mark) technology available from Perkin Elmer. Results from these studies can provide an indication of the normal function of the polypeptide in the organism. In addition, comparative studies of the normal expression pattern of mRNAs with that of mRNAs encoded by an alternative form of the same gene (for example, one having an alteration in polypeptide coding potential or a regulatory mutation) can provide valuable insights into the role of the polypeptides of the present invention, or that of inappropriate expression thereof in disease. Such inappropriate expression may be of a temporal, spatial or simply quantitative nature. A further aspect of the present invention relates to antibodies. The polypeptides of the invention or their fragments, or cells expressing them, can be used as immunogens to produce antibodies that are immunospecific for polypeptides of the present invention. The term "immunospecific" means that the antibodies have substantially greater affinity for the polypeptides of the invention than their affinity for other related polypeptides in the prior art. Antibodies generated against polypeptides of the present invention may be obtained by administering the polypeptides or epitope-bearing fragments, or cells to an animal, preferably a non-human animal, using routine protocols. For preparation of monoclonal antibodies, any technique which provides antibodies produced by continuous cell line cultures can be used. Examples include the hybridoma technique (Kohler, G. and Milstein, C, Nature (1975) 256:495-497), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Immunology Today (1983) 4:72) and the EBV- hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, 77-96, Alan R. Liss, Inc., 1985). Techniques for the production of single chain antibodies, such as those described in U.S. Patent No. 4,946,778, can also be adapted to produce single chain antibodies to polypeptides of this invention. Also, transgenic mice, or other organisms, including other mammals, may be used to express humanized antibodies. The above-described antibodies may be employed to isolate or to identify clones expressing the polypeptide or to purify the polypeptides by affinity chromatography. Antibodies against polypeptides of the present invention may also be employed to treat diseases of the invention, amongst others. Polypeptides and polynucleotides of the present invention may also be used as vaccines. Accordingly, in a further aspect, the present invention relates to a method for inducing an immunological response in a mammal that comprises inoculating the mammal with a polypeptide of the present invention, adequate to produce antibody and/or T cell immune response, including, for example, cytokine-producing T cells or cytotoxic T cells, to protect said animal from disease, whether that disease is already established within the individual or not. An immunological response in a mammal may also be induced by a method comprises delivering a polypeptide of the present invention via a vector directing expression of the polynucleotide and coding for the polypeptide in vivo in order to induce such an immunological response to produce antibody to protect said animal from diseases of the invention. One way of administering the vector is by accelerating it into the desired cells as a coating on particles or otherwise. Such nucleic acid vector may comprise DNA, RNA, a modified nucleic acid, or a DNA/RNA hybrid. For use a vaccine, a polypeptide or a nucleic acid vector will be normally provided as a vaccine formulation (composition). The formulation may further comprise a suitable carrier. Since a polypeptide may be broken down in the stomach, it is preferably administered parenterally (for instance, subcutaneous, intra-muscular, intravenous, or intra-dermal injection). Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions that may contain anti-oxidants, buffers, bacteriostats and solutes that render the formulation instonic with the blood of the recipient; and aqueous and non-aqueous sterile suspensions that may include suspending agents or thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampoules and vials and may be stored in a freeze-dried condition requiring only the addition of the sterile liquid carrier immediately prior to use. The vaccine formulation may also include adjuvant systems for enhancing the immunogenicity of the formulation, such as oil-in water systems and other systems known in the art. The dosage will depend on the specific activity of the vaccine and can be readily determined by routine experimentation. Polypeptides of the present invention have one or more biological functions that are of relevance in one or more disease states, in particular the diseases of the invention hereinbefore mentioned. It is therefore useful to identify compounds that stimulate or inhibit the function or level of the polypeptide. Accordingly, in a further aspect, the present invention provides for a method of screening compounds to identify those that stimulate or inhibit the function or level of the polypeptide. Such methods identify agonists or antagonists that may be employed for therapeutic and prophylactic purposes for such diseases of the invention as hereinbefore mentioned. Compounds may be identified from a variety of sources, for example, cells, cell-free preparations, chemical libraries, collections of chemical compounds, and natural product mixtures. Such agonists or antagonists so-identified may be natural or modified substrates, ligands, receptors, enzymes, etc., as the case may be, of the polypeptide; a structural or functional mimetic thereof (see Coligan et al., Current Protocols in Immunology l(2):Chapter 5 (1991)) or a small molecule. Such small molecules preferably have a molecular weight below 2,000 daltons, more preferably between 300 and 1,000 daltons, and most preferably between 400 and 700 daltons. It is preferred that these small molecules are organic molecules. The screening method may simply measure the binding of a candidate compound to the polypeptide, or to cells or membranes bearing the polypeptide, or a fusion protein thereof, by means of a label directly or indirectly associated with the candidate compound. Alternatively, the screening method may involve measuring or detecting (qualitatively or quantitatively) the competitive binding of a candidate compound to the polypeptide against a labeled competitor (e.g. agonist or antagonist). Further, these screening methods may test whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide, using detection systems appropriate to the cells bearing the polypeptide. Inhibitors of activation are generally assayed in the presence of a known agonist and the effect on activation by the agonist by the presence of the candidate compound is observed. Further, the screening methods may simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide of the present invention, to form a mixture, measuring an activity of the genes set forth in Table I in the mixture, and comparing activity of the mixture of the genes set forth in Table I to a control mixture which contains no candidate compound. Polypeptides of the present invention may be employed in conventional low capacity screening methods and also in high-throughput screening (HTS) formats. Such HTS formats include not only the well-established use of 96- and, more recently, 384- well micotiter plates but also emerging methods such as the nanowell method described by Schullek et al, Anal Biochem., 246, 20-29, (1997). Fusion proteins, such as those made from Fc portion and polypeptide of the genes set forth in Table I, as hereinbefore described, can also be used for high-throughput screening assays to identify antagonists for the polypeptide of the present invention (see D. Bennett et al, J Mol Recognition, 8:52-58 (1995); and K. Johanson et al., J Biol Chem, 270(16):9459-9471 (1995)). The polynucleotides, polypeptides and antibodies to the polypeptide of the present invention may also be used to configure screening methods for detecting the effect of added compounds on the production of mRNA and polypeptide in cells. For example, an ELISA assay may be constructed for measuring secreted or cell associated levels of polypeptide using monoclonal and polyclonal antibodies by standard methods known in the art. This can be used to discover agents that may inhibit or enhance the production of polypeptide (also called antagonist or agonist, respectively) from suitably manipulated cells or tissues. A polypeptide of the present invention may be used to identify membrane bound or soluble receptors, if any, through standard receptor binding techniques known in the art. These include, but are not limited to, ligand binding and crosslinking assays in which the polypeptide is labeled with a radioactive isotope (for instance, ^^1), chemically modified (for instance, biotinylated), or fused to a peptide sequence suitable for detection or purification, and incubated with a source of the putative receptor (cells, cell membranes, cell supernatants, tissue extracts, bodily fluids). Other methods include biophysical techniques such as surface plasmon resonance and spectroscopy. These screening methods may also be used to identify agonists and antagonists of the polypeptide that compete with the binding of the polypeptide to its receptors, if any. Standard methods for conducting such assays are well understood in the art. Examples of antagonists of polypeptides of the present invention include antibodies or, in some cases, oligonucleotides or proteins that are closely related to the ligands, substrates, receptors, enzymes, etc., as the case may be, of the polypeptide, e.g., a fragment of the ligands, substrates, receptors, enzymes, etc.; or a small molecule that bind to the polypeptide of the present invention but do not elicit a response, so that the activity of the polypeptide is prevented. Screening methods may also involve the use of transgenic technology and the genes set forth in Table I. The art of constructing transgenic animals is well established. For example, the genes set forth in Table I may be introduced through microinjection into the male pronucleus of fertilized oocytes, retroviral transfer into pre- or post-implantation embryos, or injection of genetically modified, such as by electroporation, embryonic stem cells into host blastocysts. Particularly useful transgenic animals are so-called "knock-in" animals in which an animal gene is replaced by the human equivalent within the genome of that animal. Knock-in transgenic animals are useful in the drug discovery process, for target validation, where the compound is specific for the human target. Other useful transgenic animals are so-called "knock-out" animals in which the expression of the animal ortholog of a polypeptide of the present invention and encoded by an endogenous DNA sequence in a cell is partially or completely annulled. The gene knock-out may be targeted to specific cells or tissues, may occur only in certain cells or tissues as a consequence of the limitations of the technology, or may occur in all, or substantially all, cells in the animal. Transgenic animal technology also offers a whole animal expression- cloning system in which introduced genes are expressed to give large amounts of polypeptides of the present invention Screening kits for use in the above described methods form a further aspect of the present invention. Such screening kits comprise: (a) a polypeptide of the present invention; (b) a recombinant cell expressing a polypeptide of the present invention; (c) a cell membrane expressing a polypeptide of the present invention; or (d) an antibody to a polypeptide of the present invention; which polypeptide is preferably that set forth in the Sequence Listing. It will be appreciated that in any such kit, (a), (b), (c) or (d) may comprise a substantial component. Glossary The following definitions are provided to facilitate understanding of certain terms used frequently hereinbefore. "Antibodies" as used herein includes polyclonal and monoclonal antibodies, chimeric, single chain, and humanized antibodies, as well as Fab fragments, including the products of an Fab or other immunoglobulin expression library. "Isolated" means altered "by the hand of man" from its natural state, i.e., if it occurs in nature, it has been changed or removed from its original environment, or both. For example, a polynucleotide or a polypeptide naturally present in a living organism is not "isolated," but the same polynucleotide or polypeptide separated from the coexisting materials of its natural state is "isolated", as the term is employed herein. Moreover, a polynucleotide or polypeptide that is introduced into an organism by transformation, genetic manipulation or by any other recombinant method is "isolated" even if it is still present in said organism, which organism may be living or non-living. "Secreted protein activity or secreted polypeptide activity" or "biological activity of the secreted protein or secreted polypeptide" refers to the metabolic or physiologic function of said secreted protein including similar activities or improved activities or these activities with decreased undesirable side-effects. Also included are antigenic and immunogenic activities of said secreted protein. "Secreted protein gene" refers to a polynucleotide comprising any of the attached nucleotide sequences or allelic variants thereof and/or their complements. "Polynucleotide" generally refers to any polyribonucleotide (RNA) or polydeoxribonucleotide (DNA), which may be unmodified or modified RNA or DNA. "Polynucleotides" include, without limitation, single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double- stranded or a mixture of single- and double-stranded regions. In addition, "polynucleotide" refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term "polynucleotide" also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications may be made to DNA and RNA; thus, "polynucleotide" embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. "Polynucleotide" also embraces relatively short polynucleotides, often referred to as oligonucleotides. "Polypeptide" refers to any polypeptide comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres. "Polypeptide" refers to both short chains, commonly referred to as peptides, oligopeptides or oligomers, and to longer chains, generally referred to as proteins. Polypeptides may contain amino acids other than the 20 gene-encoded amino acids. "Polypeptides" include amino acid sequences modified either by natural processes, such as post-translational processing, or by chemical modification techniques that are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature.' Modifications may occur anywhere in a polypeptide, including the peptide backbone, the amino acid side- chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present to the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched and branched cyclic polypeptides may result from post-translation natural processes or may be made by synthetic methods. Modifications include acetylation, acylation, ADP-ribosylation, amidation, biotinylation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cystine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, and ubiquitination (see, for instance, Proteins - Structure and Molecular Properties, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York, 1993; Wold, F., Post-translational Protein Modifications: Perspectives and Prospects, 1-12, in Post-translational Covalent Modification of Proteins, B. C. Johnson, Ed., Academic Press, New York, 1983; Seifter et al., "Analysis for protein modifications and nonprotein cofactors", Meth Enzymol, 182, 626-646, 1990, and Rattan et al, "Protein Synthesis: Post-translational Modifications and Aging", Ann NY Acad Sci, 663, 48-62, 1992). "Fragment" of a polypeptide sequence refers to a polypeptide sequence that is shorter than the reference sequence but that retains essentially the same biological function or activity as the reference polypeptide. "Fragment" of a polynucleotide sequence refers to a polynucleotide sequence that is shorter than the reference sequence set forth in the Sequence Listing. "Variant" refers to a polynucleotide or polypeptide that differs from a reference polynucleotide or polypeptide, but retains the essential properties thereof. A typical variant of a polynucleotide differs in nucleotide sequence from the reference polynucleotide. Changes in the nucleotide sequence of the variant may or may not alter the amino acid sequence of a polypeptide encoded by the reference polynucleotide. Nucleotide changes may result in amino acid substitutions, additions, deletions, fusions and truncations in the polypeptide encoded by the reference sequence, as discussed below. A typical variant of a polypeptide differs in amino acid sequence from the reference polypeptide. Generally, alterations are limited so that the sequences of the reference polypeptide and the variant are closely similar overall and, in many regions, identical. A variant and reference polypeptide may differ in amino acid sequence by one or more substitutions, insertions, deletions in any combination. A substituted or inserted amino acid residue may or may not be one encoded by the genetic code. Typical conservative substitutions include Gly, Ala; Val, He, Leu; Asp, Glu; Asn, Gin; Ser, Thr; Lys, Arg; and Phe and Tyr. A variant of a polynucleotide or polypeptide may be naturally occurring such as an allele, or it may be a variant that is not known to occur naturally. Non-naturally occurring variants of polynucleotides and polypeptides may be made by mutagenesis techniques or by direct synthesis. Also included as variants are polypeptides having one or more post-translational modifications, for instance glycosylation, phosphorylation, methylation, ADP ribosylation and the like. Embodiments include methylation of the N-terminal amino acid, phosphorylations of serines and threonines and modification of C-terminal glycines. "Allele" refers to one of two or more alternative forms of a gene occurring at a given locus in the genome. "Polymorphism" refers to a variation in nucleotide sequence (and encoded polypeptide sequence, if relevant) at a given position in the genome within a population. "Single Nucleotide Polymorphism" (SNP) refers to the occurrence of nucleotide variability at a single nucleotide position in the genome, within a population. An SNP may occur within a gene or within intergenic regions of the genome. SNPs can be assayed using Allele Specific Amplification (ASA). For the process at least 3 primers are required. A common primer is used in reverse complement to the polymorphism being assayed. This common primer can be between 50 and 1500 bps from the polymorphic base. The other two (or more) primers are identical to each other except that the final 3' base wobbles to match one of the two (or more) alleles that make up the polymorphism. Two (or more) PCR reactions are then conducted on sample DNA, each using the common primer and one of the Allele Specific Primers. "Splice Variant" as used herein refers to cDNA molecules produced from RNA molecules initially transcribed from the same genomic DNA sequence but which have undergone alternative RNA splicing. Alternative RNA splicing occurs when a primary RNA transcript undergoes splicing, generally for the removal of introns, which results in the production of more than one mRNA molecule each of that may encode different amino acid sequences. The term splice variant also refers to the proteins encoded by the above cDNA molecules. "Identity" reflects a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, determined by comparing the sequences. In general, identity refers to an exact nucleotide to nucleotide or amino acid to amino acid correspondence of the two polynucleotide or two polypeptide sequences, respectively, over the length of the sequences being compared. "% Identity" - For sequences where there is not an exact correspondence, a "% identity" may be determined. In general, the two sequences to be compared are aligned to give a maximum correlation between the sequences. This may include inserting "gaps" in either one or both sequences, to enhance the degree of alignment. A % identity may be determined over the whole length of each of the sequences being compared (so- called global alignment), that is particularly suitable for sequences of the same or very similar length, or over shorter, defined lengths (so-called local alignment), that is more suitable for sequences of unequal length. "Similarity" is a further, more sophisticated measure of the relationship between two polypeptide sequences. In general, "similarity" means a comparison between the amino acids of two polypeptide chains, on a residue by residue basis, taking into account not only exact correspondences between a between pairs of residues, one from each of the sequences being compared (as for identity) but also, where there is not an exact correspondence, whether, on an evolutionary basis, one residue is a likely substitute for the other. This likelihood has an associated "score" from which the "% similarity" of the two sequences can then be determined. Methods for comparing the identity and similarity of two or more sequences are well known in the art. Thus for instance, programs available in the Wisconsin Sequence Analysis Package, version 9.1 (Devereux J et al, Nucleic Acids Res, 12, 387-395, 1984, available from Genetics Computer Group, Madison, Wisconsin, USA), for example the programs BESTFJ and GAP, may be used to determine the % identity between two polynucleotides and the % identity and the % similarity between two polypeptide sequences. BESTFIT uses the "local homology" algorithm of Smith and Waterman (J Mol Biol, 147,195-197, 1981, Advances in Applied Mathematics, 2, 482-489, 1981) and finds the best single region of similarity between two sequences. BESTFIT is more suited to comparing two polynucleotide or two polypeptide sequences that are dissimilar in length, the program assuming that the shorter sequence represents a portion of the longer. In comparison, GAP aligns two sequences, finding a "maximum similarity", according to the algorithm of Neddleman and Wunsch (J Mol Biol, 48, 443-453, 1970). GAP is more suited to comparing sequences that are approximately the same length and an alignment is expected over the entire length. Preferably, the parameters "Gap Weight" and "Length Weight" used in each program are 50 and 3, for polynucleotide sequences and 12 and 4 for polypeptide sequences, respectively. Preferably, % identities and similarities are determined when the two sequences being compared are optimally aligned. Other programs for determining identity and/or similarity between sequences are also known in the art, for instance the BLAST family of programs (Altschul S F et al, J Mol Biol, 215, 403-410, 1990, Altschul S F et al, Nucleic Acids Res., 25:389-3402, 1997, available from the National Center for Biotechnology Information (NCBI), Bethesda, Maryland, USA and accessible through the home page of the NCBI at www.ncbi.nlm.nih.gov) and FASTA (Pearson W R, Methods in Enzymology, 183, 63-99, 1990; Pearson W R and Lipman D J, Proc Nat Acad Sci USA, 85, 2444-2448,1988, available as part of the Wisconsin Sequence Analysis Package). Preferably, the BLOSUM62 amino acid substitution matrix (Henikoff S and Henikoff J G, Proc. Nat. Acad Sci. USA, 89, 10915-10919, 1992) is used in polypeptide sequence comparisons including where nucleotide sequences are first translated into amino acid sequences before comparison. Preferably, the program BESTFIT is used to determine the % identity of a query polynucleotide or a polypeptide sequence with respect to a reference polynucleotide or a polypeptide sequence, the query and the reference sequence being optimally aligned and the parameters of the program set at the default value, as hereinbefore described. "Identity Index" is a measure of sequence relatedness which may be used to compare a candidate sequence (polynucleotide or polypeptide) and a reference sequence. Thus, for instance, a candidate polynucleotide sequence having, for example, an Identity Index of 0.95 compared to a reference polynucleotide sequence is identical to the reference sequence except that the candidate polynucleotide sequence may include on average up to five differences per each 100 nucleotides of the reference sequence. Such differences are selected from the group consisting of at least one nucleotide deletion, substitution, including transition and transversion, or insertion. These differences may occur at the 5' or 3' terminal positions of the reference polynucleotide sequence or anywhere between these terminal positions, interspersed either individually among the nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence. In other words, to obtain a polynucleotide sequence having an Identity Index of 0.95 compared to a reference polynucleotide sequence, an average of up to 5 in every 100 of the nucleotides of the in the reference sequence may be deleted, substituted or inserted, or any combination thereof, as hereinbefore described. The same applies mutatis mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99. Similarly, for a polypeptide, a candidate polypeptide sequence having, for example, an Identity Index of 0.95 compared to a reference polypeptide sequence is identical to the reference sequence except that the polypeptide sequence may include an average of up to five differences per each 100 amino acids of the reference sequence. Such differences are selected from the group consisting of at least one amino acid deletion, substitution, including conservative and non-conservative substitution, or insertion. These differences may occur at the amino- or carboxy-terminal positions of the reference polypeptide sequence or anywhere between these terminal positions, interspersed either individually among the amino acids in the reference sequence or in one or more contiguous groups within the reference sequence. In other words, to obtain a polypeptide sequence having an Identity Index of 0.95 compared to a reference polypeptide sequence, an average of up to 5 in every 100 of the amino acids in the reference sequence may be deleted, substituted or inserted, or any combination thereof, as hereinbefore described. The same applies mutatis mutandis for other values of the Identity Index, for instance 0.96, 0.97, 0.98 and 0.99. The relationship between the number of nucleotide or amino acid differences and the Identity Index may be expressed in the following equation: n a ≤ x a - (x a » I), in which: n a is the number of nucleotide or amino acid differences, x a is the total number of nucleotides or amino acids in a sequence set forth in the Sequence Listing, I is the Identity Index, • is the symbol for the multiplication operator, and in which any non-integer product of x a and I is rounded down to the nearest integer prior to subtracting it from x a . "Homolog" is a generic term used in the art to indicate a polynucleotide or polypeptide sequence possessing a high degree of sequence relatedness to a reference sequence. Such relatedness may be quantified by determining the degree of identity and/or similarity between the two sequences as hereinbefore defined. Falling within this generic term are the terms "ortholog", and "paralog". "Ortholog" refers to a polynucleotide or polypeptide that is the functional equivalent of the polynucleotide or polypeptide in another species. "Paralog" refers to a polynucleotideor polypeptide that within the same species which is functionally similar. "Fusion protein" refers to a protein encoded by two, often unrelated, fused genes or fragments thereof. In one example, EP-A-0464 533-A discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof. In many cases, employing an immunoglobulin Fc region as a part of a fusion protein is advantageous for use in therapy and diagnosis resulting in, for example, improved pharmacokinetic properties [see, e.g., EP-A 0232 262]. On the other hand, for some uses it would be desirable to be able to delete the Fc part after the fusion protem has been expressed, detected and purified. All publications and references, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference in their entirety as if each individual publication or reference were specifically and individually indicated to be incorporated by reference herein as being fully set forth. Any patent application to which this application claims priority is also incorporated by reference herein in its entirety in the manner described above for publications and references. Table I. Table I (cont). Table II Table II (cont). Table II (cont). Table II cont. Table II cont. Table II cont). Table II cont. Table II (cont). Table II (cont). Table III Table III (cont). Table III (cont). Gene Name Uses Associated Diseases sbgl521449 An embodiment of the invention is the use of Cardiovascular connexin sbgl521449connexin in the propagation of the action disease, osteogenesis, potential from the conduction system to the working and wound healing myocardium. Close homologues of disorders sbgl521449connexin include connexin 43 and connexin 45. Two members of the connexin family of gap junction proteins, connexin 43 (Cx43; Gj alpha 1) and Table III (cont). adhesion or receptor-ligand binding. Close homologues hematopoietic of sbgl8525LRRb are connectin, slit, chaoptin, and toll. disorder, wound It is likely that leucine-rich repeat (LRR) proteins such healing disorder, as connectin, slit, chaoptin, and toll have important roles inflammation, in neuronal development and the adult nervous system gastrointestinal as cell adhesion molecules (Taguchi A, Wanaka A, Mori ulceration, and T, Matsumoto K, Imai Y, Tagaki T, Tohyama M, 1996, diseases in spinal Brain Res Mol Brain Res; 35:31-4). At least one LRR cord, thyroid gland, was shown to be specifically expressed on B cells, heart, trachea, suggesting its role in immunization (Miyake K, thymus, lymph Yamashita Y, Ogata M, Sudo T, Kimoto M, 1995. J node, muscular Immunol 154:3333-40). Some studies have shown that system, and nervous brain injury can cause overexepression of neuronal system LRR, suggesting that neuronal LRR may be an important component of the pathophysiological response to brain injury (Ishii N, Wanaka A, Tohyama M, 1996, Brain Res Mol Brain Res 40: 148-52). SBhACRP30 An embodiment of the invention is the use of Cancer, obesity, c SBhACRP30c in regulating inflammation, cell anorexia, proliferation, cell death, immunity, and/or energy inflammation , homeostatis. Close homologues of SBhACRP30c are cardiovadcular ACRP30, chipmunk Hib27, Clq complement proteins, disease, growth TNF, and other members of the TNF superfamily. abnormalities ACRP30 (Adipocyte Complement-Related Protein of 30 kDa) is made exclusively in adipocytes, and its expression is dysregulated in various forms of obesity (Hu, E, Liang, P and Spiegelman, BM. J. Biol. Chem 271, 10697-10703, 1996). ACRP30 secretion is acutely stimulated by insulin (Scherer, PE, Williams S., Fogliano, M., Baldini, G. and Lodish, J Biol. Chem. 270, 26746-26749, 1995) and is repressed by chronically elevated levels of insulin. A related molecule, the Hib27 protein from Siberian chipmunks, seems also to be involved in energy homeostasis, as its expression is specifically extinguished during hibernation (Takamatsu, N., Ohba, K, Kondo, J.,Kondo, N., and Shiba, T. Mol. Cell Biol.13 1516-1521, 1993). Recently, it has been shown that the three dimensional structure of ACRP30 is superimposible with that of the TNF's, suggesting that these proteins may have a similar function and mode of action (Shapiro, L and Scherer PE., Current Biology 8, 335-338, 1997). TNF's are known to play a role in energy homeostasis, where they are implicated in cachexia, obesity and in insulin resistance (Hotamisligil GS., and Spiegelman BM. Diabetes (1994) 43, 1271-1278; Teoman Uysal K., Wiesbrock SM, Marina MW and Hotamisligil GS., Nature 389, 610-614, 1997). Based on EST expression data, SBHACRP30a is primarily or exclusively expressed in heart. sbgl23493SL An embodiment of the invention is the use of Diseases in spinal ITc sbgl 23493 SLITc, a secreted protein, in preventing and cord, thyroid gland, treatment of diseases in spinal cord, thyroid gland, ovary, prostate, ovary, prostate, renal gland, small intestine, heart, renal gland, small trachea, thymus, lymph node, muscular system and intestine, heart, colon. Close homologues of sbgl23493SLITc are rat trachea, thymus, slit protein and pineal gland specific gene-1 protein. lymph node, Table IV. Quantitative, Tissue-specific mRNA expression detected using SybrMan Quantitative, tissue-specific, mRNA expression patterns of the genes were measured using SYBR- Green Quantitative PCR (Applied Biosystems, Foster City, CA; see Schmittgen T.D. et al., Analytical Biochemistry 285:194-204, 2000) and human cDNAs prepared from various human tissues. Gene-specific PCR primers were designed using the first nucleic acid sequence listed in the Sequence List for each gene. The threshold cycle (C t ) is defined as the fractional cycle number at which the reporter fluorescence generated by cleavage of the probe reaches a threshold defined as 10 times the background. In cases sequence detection system software predicted more than one PCR product, Taqman was used for the specific PCR amplification as indicated under the specific genes. In each gene's first subset table, two replicate measurements of gene of identification (GOI) mRNA were measured from various human tissues (column 3 and 4). The average GOI mRNA copies ofthe two replicates were made from each tissue RNA (column 5). The average amount of 18S rRNA from each tissue RNA was measured (column 6) and used for normalization. To make each tissue with the same amount of 50 ng of 18S rRNA, the normalization factor (column 7) was calculated by dividing 50 ng with the amount of 18S rRNA measured from each tissue (column 6). The mRNA copies per 50 ng of total RNA were obtained by multipling each GOI normalization factor and the average mRNA copies (columnδ). Fold changes shown in each gene's second subset table were only calculated for disease tissues which have a normal counterpart. There are blanks in the fold change column for all samples that do not have counterparts. In addition, the fold change calculations are the fold change in the disease sample as compared to the normal sample. Accordingly, there will not be a fold change calculation next to any ofthe normal samples. For patient matched cancer pairs (colon, lung, and breast), each tumor is compared to its specific normal counterpart. When patient-matched normal/disease pairs do not exist, each disease sample was compared back to the average of all the normal samples of that same tissue type. For example, normal brain from the same patient that provided Alzheimer's brain is not applicable . Three normal brain samples and 4 Alzheimer's brain samples are used in the fold change. Three normal samples were averaged, and each of the Alzheimer's samples was compared back to that average. Abbreviations ALZ Alzheimer's Disease CT CLONTECH (1020 East Meadow Circle Palo Alto, CA 94303-4230, USA) KC Sample prepared by GSK investigator COPD chronic obstructive pulmonary disease endo endothelial VEGF vascular endothelial growth factor bFGF basic fibroblast growth factor BM bone marrow osteo osteoblast OA osteoarthritis RA rheumatoid arthritis PBL peripheral blood lymphocytes PBMNC peripheral blood mononuclear cells HIV human immunodeficiency virus HSV Herpes simplex virus HPV human papilloma virus Gene Name sbgl571549cystatin-re Moderate to low overall expression. Highest normal expression is seen in the whole brain, hypothalamus, liver, head of pancreas, small intestine, and uterus. This pattern of expression suggests that this gene may be involved in diabetes or other metabolic diseases. Highest disease expression is seen in the normal/tumor breast samples as well as in the RA and OA synovium samples. Upregulation in 2 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in 2 of 4 Alzheimer's brain samples suggests involvement in Alzheimer's disease. Downregulation in 3 of 3 COPD samples and in 2 of 4 asthmatic lung samples suggests a potential role for this gene in chronic obstructive pulmonary disorder and asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Downregulation in the HIV-infected PBL cells and in the HSV- infected MRC5 cells suggests a role for this gene in HIV and HSV. Gene Name sbgl571549cystatin-re Gene Name sbgl558434SRCR Moderate to low overall expression. This gene is expressed fairly ubiquitously in all normal samples analyzed with the highest levels of expression seen in the whole brain, fetal brain, endometrium, and parotid gland. Highest disease expression is seen in the normal and Alzheimer's brain samples and in the RA and OA bone samples. Upregulation in 2 of 4 breast tumor samples implicates this gene in breast cancer. Downregulation in 1 of 3 COPD samples and in 1 of 4 asthmatic lung samples suggests a potential role for this gene in chronic obstructive pulmonary disorder and asthma. Downregulation in the HIV-infected PBL cells and in the HSV-infected MRC5 cells suggests a role for this gene in HIV and HSV. Gene Name sbgl558434SRCR Gene Name sbgl546354LRR This primer set was shown to amplify two products of approximately equal proportions by the dissociation curve program. Moderate to low overall expression. Highest normal expression is seen in the whole brain, endometrium, and uterus. Good levels of expression are seen in all of the samples representing the female reproductive system. Highest disease expression is seen in the normal and Alzheimer's brain samples. Downregulation in 2 of 4 lung tumors and upregulation in 3 of 4 breast tumors implicates this gene in cancers of the lung and breast. Downregulation in 1 of 4 Alzheimer's brain samples may suggest a role in Alzheimer's disease. Downregulation in 3 of 3 COPD samples and in 3 of 4 asthmatic lung samples suggests a potential role for this gene in chronic obstructive pulmonary disorder and asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Upregulation in the OA cartilage sample suggests a possible role for this gene in osteoarthritis. Gene Name sbgl546354LRR Gene Name sbgl 555869CABP Failed. Gene Name sbgl518024NKR Moderate to low overall expression. The highest normal expression is seen in the liver with lower levels of expression in the tissues specific to the female reproductive system including the uterus, cervix, endometrium, myometrium, and the ovary. The highest disease expression is seen in the HIV-infected and uninfected peripheral blood lymphocytes. Upregulation in 2 of 4 colon tumor samples implicates this gene in colon cancer. Downregulation in 2 of 4 lung tumor samples suggests a potential role in cancer of the lung. Upregulation in 1 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in the VEGF-treated endothelial cell line implicates a possible role for this gene in angiogenesis. Upregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. Moderate to high expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in the PBMNCs, B cells, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl518024NKR Gene Name sbgl525809WNT8 Low overall expression. The highest normal expression is seen in the whole brain, testis, liver, parotid gland, and thymus. Some of the tissues representing the GI tract including the colon and the jejunum are represented as well as some of the tissue of the female reproductive system including the endometrium, ovary, and uterus. The highest disease expression is seen in the normal and disease brain samples. Upregulation in 1 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. Gene Name sbgl525809WNT8 Gene Name sbgl519904cdk Moderate to high overall expression. The highest normal expression is seen in the whole brain, fetal liver, and thymus. Additional high expression is seen in the subcutaneous adipocytes, the salivary gland and many of the tissues representing the female reproductive system including the mammary gland, the placenta, and the myometrium. This gene is expressed fairly ubiquitously in the disease samples with the highest expression seen in the T cells, uninfected PBLs, and the W12 cells. Upregulation in 2 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in 1 of 4 asthmatic lung samples indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Upregulated in the stimulated bone marrow and the differentiated osteoblasts. May be implicated in diseases of the bone such as osteoporosis. Downregulation in the HIV-infected PBLs and the HSV-infected MRC5 cells suggests that this gene may be a host factor in HIV and HSV. Gene Name sbgl519904cdk Gene Name sbgl521449connexin Moderate to low overall expression. This gene is expressed fairly ubiquitously in the normal samples with highest levels of expression seen in the whole brain, hypothalamus, liver, fetal liver, and thymus. The highest disease expression is seen in the breast, colon, and lung normal and tumor samples and in the normal and disease brain samples. Upregulation in 2 of 4 breast tumor samples implicates this gene in breast cancer. Downregulation in 2 of 4 asthmatic lung samples indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Moderate to high expression in the RA and OA synovium samples and the chondrocytes with corroborating high expression in the T cells, B cells, dendritic cells, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl521449connexin Gene Name sbgl522659Siglec (Taqman was performed for this sample) Moderate to high overall expression. The highest normal expression is seen in the myometrium, ovary, adrenal gland, whole brain, spleen, and fetal liver. The other tissues representing both the GI tract and the female reproductive system also show high expression. These tissues include the jejunum, omentum, small intestine, rectum, stomach, endometrium, and placenta. The GI pattern of expression suggests that this gene may be involved in diseases of the digestive tract such as IBS and Crohn's Disease. The highest disease expression is seen in the Clontech normal lung sample, some of the asthmatic lung samples, the Clontech normal heart sample, and all of the OA samples. Upregulation in 2 of 4 lung tumor samples implicates this gene in lung cancer. Downregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non- obstructive and obstructive DCM and ischemia. Upregulated in the stimulated bone marrow sample. Downregulation in the OA cartilage pool suggests that this gene may be involved in or a consequence of osteoarthritis. Upregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. Upregulation in the W12 cells suggests that this gene may be a host factor in HPV. Gene Name sbgl522659Siglec Gene Name sbgl528389ITI Moderate overall expression. This gene is expressed fairly ubiquitously in the normal samples with the highest expression seen in the whole brain, lung, thymus, and testis. The highest disease expression is seen in some of the colon, breast, and lung normal and tumor samples as well as in the asthmatic lung samples. Upregulation in 2 of 4 colon tumor samples implicates this gene in colon cancer. Upregulation in 2 of 4 asthmatic lung samples indicates a possible involvement in asthma. Upregulation in the HIV-infected PBLs cells suggests that this gene may be a host factor in HIV. Upregulation in the OA cartilage pool and high expression in the RA and OA synovium samples, and the OA bone samples with corroborating high expression in the T cells, B cells, and neutrophils, dendritic cells, and the eosinophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl528389ITI Gene Name sbgl526964ISLR Moderate overall expression. The highest normal expression is seen in the subcutaneous adipocytes, whole brain, fetal brain, liver, thymus, and fetal liver. Additional expression is seen in the colon and rectum. The highest disease expression is seen in the breast, colon, and lung normal and tumor samples as well as in the dendritic cell, the eosinophils, and the uninfected PBLs. Upregulation in 1 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in 3 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Upregulation in 4 of 4 asthmatic lung samples indicates a possible involvement in asthma. Upregulated in the stimulated bone marrow and the differentiated osteoblasts. Downregulation in the HIV-infected PBLs and the HSV-infected MRC5 cells suggests that this gene may be a host factor in HIV and HSV. Downregulation in the W12 cells suggests that this gene may be a host factor in HPV. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in the T cells, B cells, neutrophils, dendritic cells, and the eosinophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl526964ISLR Gene Name sbgl539439TSPK Moderate to low overall expression. The highest normal expression is seen in the whole brain, testis, endometrium, and trachea. The highest disease expression is seen in one of the lung tumor samples, one of the breast tumor samples, and one of the normal breast samples. Upregulation in 1 of 4 colon tumor samples, 1 of 4 lung tumor samples, and 1 of 4 breast tumor samples implicates this gene in cancers of the colon, lung, and breast. Upregulation in 1 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Downregulation in the VEGF and bFGF- treated endothelial cells suggests an involvement in angiogenesis. Upregulation in 2 of 3 disease heart samples implies an involvement in cardiovascular diseases such as obstructive DCM and ischemia. Downregulated in the differentiated osteoblasts. Downregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. Gene Name sbgl539439TSPK Gene Name sbgl5713491ipase Highly specific overall expression. The highest normal expression is seen in the whole brain, colon, and rectum with additional high expression in other GI tract-specific tissues including the ileum and the jejunum. This pattern of expression suggests that this gene may be involved in diseases ofthe digestive tract such as IBS. The highest disease expression is seen in the colon normal and tumor samples. Large upregulation in 1 of 4 colon tumor samples is sufficient to make a claim for colon cancer. Upregulation in 1 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Upregulation in the HIV- infected PBL cells suggests that this gene may be a host factor in HIV. Upregulation in the W12 cells suggests that this gene may be a host factor in HPV. Gene Name sbgl5713491ipase Gene Name sbgl565539aCONNEXIN Failed Gene Name sbgl565539bCONNEXIN Highly specific overall expression. The highest normal expression is seen primarily in tissues representing the female reproductive system including the endometrium, ovary, placenta, and uterus as well as tissues representing the GI tract such as the colon, ileum, jejunum, omentum, and stomach. Additional high expression is seen in the whole brain and the liver. Highest disease" expression is specific to the Alzheimer's brain samples. Upregulation in 2 of 3 disease heart samples implies an involvement in cardiovascular diseases such as obstructive DCM and ischemia. Upregulated in the differentiated osteoblasts. Downregulation in the HIV-infected PBLs and the HSV-infected MRC5 cells suggests that this gene may be a host factor in HIV and HSV. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in the T cells, B cells, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Upregulation in the W12 cells suggests that this gene may be a host factor in HPV. Gene Name sbg!565539bCONNEXIN Gene Name sbgl563294acadherin Moderate to low overall expression. The highest normal expression is seen in the whole brain, prostate, thymus, and trachea. The highest disease expression is seen in some of the colon and lung normal and tumor samples as well as in 2 of the asthmatic lung samples. Upregulation in 1 of 4 colon tumor samples and 1 of 4 lung tumor samples implicates this gene in cancers of the colon and lung. Upregulation in 3 of 4 asthmatic lung samples coupled with immune cell expression in indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. This gene appears to show the same expression patterns in the disease samples as 1563294b. Based on this, it is likely that these two different primer sets are amplifying the same gene. Gene Name sbgl563294acadherin Gene Name sbgl563294bcadherin Moderate overall expression. The highest normal expression is seen in the adrenal gland, whole brain, fetal brain, pancreas, hypothalamus, and the testis. Additional high expression is seen in the endometrium, esophagus, heart, liver, pancreas, rectum, and small intestine. This normal expression pattern suggests that this gene may be involved in certain metabolic disorders. The highest disease expression is seen in some of the colon, lung, and breast normal and tumor samples as well as in the asthmatic lung samples and the adenoid and tonsil. Large upregulation in 1 of 4 colon tumor samples is sufficient to make a claim for colon cancer. Upregulation in 1 of 4 lung tumor samples implicates this gene in cancer of the lung. Upregulation in 3 of 4 asthmatic lung samples coupled with immune cell expression in indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Downregulation in the HIV-infected PBLs and the HSV- infected MRC5 cells suggests that this gene may be a host factor in HIV and HSV. This gene appears to show the same expression patterns in the disease samples as 1563294a. Based on this, it is likely that these two different primer sets are amplifying the same gene. Gene Name sbgl563294bcadherin Gene Name sbgl563509ECM Moderate to high overall expression. This gene is expressed fairly ubiquitously throughout most of the normal tissues. The highest normal expression is seen in the lung, fetal liver, and mammary gland while the lowest normal expression is seen in the adrenal, fetal brain, hypothalamus, head of pancreas, skeletal muscle, and the testis. The highest disease expression is seen in some of the normal and tumor lung samples and in the OA and RA synovium samples. Downregulation in 1 of 4 lung tumor samples suggests a potential role in cancer of the lung. Upregulation in 1 of 4 breast tumor samples implicates this gene in breast cancer. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Downregulation in the HIV-infected PBLs and the HSV-infected MRC5 cells suggests that this gene may be a host factor in HIV and HSV. High expression in the OA and RA synovium samples with corroborating immune cell expression implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl563509ECM Gene Name sbgl552159Serprotease Moderate overall expression. The highest normal expression is seen in the whole brain, fetal brain, thymus, and testis. The highest disease expression is seen in the some of the normal counterparts of both the lung and breast tumor samples as well as in three of the asthmatic lung samples. Significant downregulation in 1 of 4 lung tumor samples and 1 of 4 breast tumor samples is sufficient to claim involvement in lung and breast cancer. Upregulation in 3 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Upregulation in 3 of 4 asthmatic lung samples with corroborating high expression in the neutrophils indicates a possible involvement in asthma. Upregulated in the differentiated osteoblasts. Downregulation in the HIV-infected PBLs and the HSV-infected MRC5 cells suggests that this gene may be a host factor in HIV and HSV. Downregulation in the W12 cells suggests that this gene may be a host factor in HPV. Gene Name sbgl552159Serprotease Gene Name sbgl551159thymosinb4 High overall expression. This gene is expressed fairly ubiquitously in the normal samples with the highest levels of expression seen in the whole brain, endometrium, myometrium, rectum, spleen, uterus, and thymus. This gene is also expressed fairly ubiquitously in the disease samples with the highest levels of expression seen in the uninfected and infected PBLs. Upregulation in 2 of 4 colon tumor samples and 1 of 4 breast tumor samples is sufficient to claim that this gene may be involved in cancers of the colon and breast. Upregulation in 1 of 4 asthmatic lung samples with corroborating high expression in all of the inflammatory immune cells indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Downregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in all of the inflammatory immune cells implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl551159thymosinb4 Gene Name SBhl686954.SOCS Moderate to high overall expression. The highest disease expression is seen in the whole brain, fetal liver, and thymus. The expression of this gene in the disease samples is fairly ubiquitous with the highest expression seen in the uninfected PBLs. Upregulation in 1 of 4 breast tumor samples implicates this gene in cancer of the breast. Upregulation in 2 of 4 asthmatic lung samples with corroborating high expression in the eosinophils and neutrophils indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Upregulated in the stimulated bone marrow. Downregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in T cells, B cells, dendritic cells, eosinophils, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name SBM686954.SOCS Gene Name sbgl548844slit Moderate overall expression. The highest normal expression is seen in the whole brain, cerebellum, and thymus. The expression in the disease samples is highly specific to most of the immune cells including the adenoid, tonsil, T cells, B cells, dendritic cells, neutrophils, eosinophils, and the uninfected peripheral blood lymphocytes. Upregulation in 3 of 4 asthmatic lung samples with corroborating high expression in the immune cells indicates a possible involvement in asthma. Upregulation in the HSV-infected MRC5 cells and the W12 cells suggests that this gene may be a host factor in HSV and HPV. High expression in the RA synovium samples with corroborating high immune cell expression implicates this gene in rheumatoid arthritis. Gene Name sbgl 548844slit Gene Name sbgl545249GGT Moderate to high overall expression. The highest normal expression is seen in the whole brain, fetal liver, jejunum, and kidney. The highest disease expression is seen in the uninfected PBLs, one of the normal lung samples, two of the lung tumor samples, one of the breast tumor samples, and one of the Alzheimer's brain samples. Upregulation in 1 of 4 asthmatic lung samples with corroborating high expression in the eosinophils and neutrophils indicates a possible involvement in asthma. Upregulated in the stimulated bone marrow and the differentiated osteoblasts. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in T cells, B cells, dendritic cells, eosinophils, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbg!545249GGT Gene Name SBhl813899.Y82017 (Taqman was performed for this sample) Moderate to low overall expression. The highest normal expression is seen in the omentum, prostate, testis, ovary, and uterus. The highest disease expression is seen in the tonsil sample suggesting that this gene may play a role in chronic ear infections and tonsillitis. Upregulation in 2 of 4 lung tumor samples implicates this gene in cancer of lung. Downregulation in 2 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Downregulation in the VEGF- and bFGF-treated endothelial cells suggests that this gene may be involved in angiogenesis. Gene Name SBhl813899.Y82017 Gene Name sbgl536324mapkkk Moderate overall expression. The highest normal expression is seen in the whole brain, cerebellum, and kidney as well as many of the tissues representing the GI tract including the colon, jejunum, rectum, and stomach. The highest disease expression is seen in many of the tumor samples and their matched normal counterparts as well as in the uninfected peripheral blood lymphocytes, W12 cells, and the normal keratinocytes. Significant upregulation in 1 of 4 colon tumor samples is sufficient to implicate this gene in colon cancer. Upregulation in 1 of 4 asthmatic lung samples with corroborating high expression in the eosinophils and neutrophils indicates a possible involvement in asthma. Upregulation in 2 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM. Upregulated in the stimulated bone marrow and the differentiated osteoblasts. Downregulation in the HIV-infected PBLs suggests that this gene may be a host factor in HIV. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in T cells, B cells, eosinophils, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl536324maρkkk Gene Name gskl810944BrCaAg Moderate to low overall expression. The highest normal expression is seen in the pancreas, prostate, and testis. The highest disease expression is seen in the normal and tumor breast samples. Upregulation in 2 of 4 colon tumors, 2 of 4 lung tumors, and 3 of 4 breast tumors implicates this gene in cancers of the colon, lung, and breast. Upregulation in 3 of 4 Alzheimer's brain samples and downregulation in 1 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Downregulated in the stimulated bone marrow. Downregulation in the HIV-infected PBLs suggests that this gene may play a role as a host factor in HIV. Upregulation in the HSV- infected MRC5 cells and the W12 cells suggests that this gene may be a host factor in HSV and HPV. Patterns of expression are very similar to gskl811484BrCaAg. Gene Name gskl810944BrCaAg Gene Name sbgl535914AIP Moderate to high overall expression. The highest normal expression is seen in the whole brain, fetal liver, and thymus. Expression in the disease samples is fairly ubiquitous with the highest levels seen in the uninfected PBLs, one of the normal brain samples, and one of the Alzheimer's brain samples. Upregulation in 3 of 4 asthmatic lung samples with corroborating high expression in the eosinophils and neutrophils indicates a possible involvement in asthma. Upregulation in 2 of 3 disease heart samples implies an involvement in cardiovascular diseases such as ischemic and obstructive DCM. Upregulated in the differentiated osteoblasts. Downregulation in the HSV-infected MRC5 cells suggests that this gene may be a host factor in HSV. High expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in all of the inflammatory immune cells implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl535914AIP Gene Name sbgl530894aCE Moderate overall expression. The highest normal expression is seen in the whole brain, fetal brain, testis, liver, omentum, parotid gland, and ovary. The highest disease expression is seen in the Alzheimer's disease brain samples. Downregulation in the VEGF-treated endothelial cells suggests that this gene may be involved in angiogenesis. Upregulation in 2 of 3 disease heart samples implies an involvement in cardiovascular diseases such as obstructive and non-obstructive DCM. Upregulated in the stimulated bone marrow. Upregulation in the HIV-infected PBLs and the W12 cells suggests that this gene may be a host factor in HIV and HPV. Moderate to high expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in the T cells and B cells implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name sbgl530894aCE Gene Name sbgl530894bCE Unlike sbgl530894aCE, Sybrman experiment failed using the primers specific for sbgl530894bCE. Taqman was performed by using the primers present in both sbgl530894aCE and sbgl530894bCE and the results is shown here as sbgl530894CE. Moderate to low overall expression. The highest normal expression is seen in the whole brain, hypothalamus, omentum, ovary, testis and uterus. The highest disease expression is seen in the Alzheimer's disease brain samples. Upregulation in 2 of 4 lung tumor samples and 2 of 4 breast tumor samples implicates this gene in cancers of the lung and breast. Downregulation in the VEGF and bFGF-treated endothelial cells suggests that this gene may be involved in angiogenesis. Upregulation in 2 of 3 disease heart samples implies an involvement in cardiovascular diseases such as ischemic and non-obstructive DCM. Downregulated in the stimulated bone marrow and the differentiated osteoblasts. Downregulation in the HIV-infected PBLs suggests that this gene may be a host factor in HIV. Gene Name sbgl530894CE Gene Name gsk.1813134.NaI Moderate to low overall expression. The highest normal expression is seen in the thyroid and trachea. The highest disease expression is seen in two of the lung tumor samples. Upregulation in 2 of 4 lung tumor samples implicates this gene in cancer of lung. Downregulation in 1 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Upregulation in 1 of 3 COPD lung samples and in 2 of 4 asthmatic lung samples implicates this gene in COPD and asthma. Gene Name gsk.1813134.NaI Gene Name gsklδl 1484BrCaAg Moderate overall expression. The highest normal expression is seen in the testis, prostate, omentum, stomach, thymus, trachea, and uterus. The highest disease expression is seen in the normal and tumor breast samples. Upregulation in 2 of 4 colon tumor samples, 2 of 4 lung tumor samples, and 2 of 4 breast tumor samples implicates this gene in cancers of the colon, lung, and breast. Downregulated in the differentiated osteoblasts. Upregulation in the HSV-infected MRC5 cells and the W12 cells suggests that this gene may be a host factor in HSV and HPV. Patterns of expression are very similar to gskl810944BrCaAg. Gene Name gsklδl 1484BrCaAg Gene Name sbgl529984aSproteinase Moderate to low overall expression. The highest normal expression is seen in the parotid gland. The highest disease expression is seen in one of the colon tumor samples and the neutrophils. Significant upregulation in 1 of 4 colon tumor samples is sufficient to implicate this gene in colon cancer. Downregulation in 2 of 4 lung tumor samples implicates this gene in lung cancer. Upregulation in 1 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Downregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Upregulated in the stimulated bone marrow. Upregulation in the HSV-infected MRC5 cells and the W12 cells suggests that this gene may be a host factor in HSV and HPV. Patterns of expression are similar to gene sbg 1529984bSproteinase Gene Name sbgl529984aSproteinase Gene Name sbgl529984bSproteinase Moderate to low overall expression. The highest normal expression is seen in the parotid gland. The highest disease expression is seen in one of the colon tumor samples and the neutrophils. Upregulation in 1 of 4 Alzheimer's brain samples suggests an involvement in Alzheimer's disease. Upregulation in 1 of 4 asthmatic lung samples with corroborating high expression in the neutrophils indicates a possible involvement in asthma. Downregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Downregulated in the OA cartilage pool may indicate some involvement in osteoarthritis. Upregulation in the HSV-infected MRC5 cells and the W12 cells suggests that this gene may be a host factor in HSV and HPV. Patterns of expression are similar to gene sbgl529984aSproteinase. Gene Name sbgl529984bSproteinase Gene Name SBGKIN113 (Taqman was performed for this sample) Moderate to low overall expression. The highest normal expression is seen in the omentum and in most ofthe samples representing the female reproductive system including the cervix, endometrium, and uterus. The highest disease expression is seen in the Alzheimer's brain samples and in the HSV-infected MRC5 cells. Significant upregulation in 1 of 4 colon tumor samples is sufficient to implicate this gene in colon cancer. Upregulation in 2 of 3 COPD lung samples and in 2 of 4 asthmatic lung samples with corroborating high expression in T cells and neutrophils implicates this gene in COPD and asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as ischemic, non-obstructive, and obstructive DCM. Downregulated in the stimulated bone marrow and the differentiated osteoblasts. Downregulation in the HIV-infected PBLs suggests that this gene may be a host factor in HIV. Upregulation in the HSV-infected MRC5 cells and the W12 cells suggests that this gene may be a host factor in HSV and HPV. Gene Name SBGKIN113 Gene Name gsk305961GDNa Moderate overall expression. The highest normal expression is seen in the whole brain, fetal liver, and thymus. This gene is expressed fairly ubiquitously in the disease samples with the highest expression seen in the normal and disease brain samples. Significant upregulation in 1 of 4 colon tumor samples is sufficient to implicate this gene in colon cancer. Upregulation in 4 of 4 asthmatic lung samples with corroborating high expression in the neutrophils indicates a possible involvement in asthma. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as ischemic, non-obstructive, and obstructive DCM. Upregulated in the stimulated bone marrow. Downregulation in the HIV-infected PBLs suggests that this gene may be a host factor in HIV. Moderate expression in the RA and OA synovium samples, the OA bone samples, and the chondrocytes with corroborating high expression in T cells, B cells, and neutrophils implicates this gene in osteoarthritis and rheumatoid arthritis. Gene Name gsk305961GDNa Gene Name gsk2402719_2395124BIG2 Moderate overall expression. The highest normal expression is seen in the whole brain, endometrium, fetal liver, rectum, and thymus. The highest disease expression is seen in the normal and disease brain samples. Downregulation in 1 of 4 colon tumor samples and 1 of 4 lung tumor samples implicates this gene in cancers of the colon and lung. Upregulation in 3 of 3 disease heart samples implies an involvement in cardiovascular diseases such as non-obstructive and obstructive DCM and ischemia. Upregulation in the HIV-infected PBLs suggests that this gene may be a host factor in HIV. Gene Name gsk2402719_2395124BIG2 Gene Name sbgl02200MCTc High to moderate overall expression. Highest normal expression in the whole brain, liver, fetal liver, and thymus. Highest disease expression in one of the colon normal/tumor pairs, one of the lung normal/tumor pairs, one of the asthmatic lung samples, the dendritic cells, and the uninfected and HIV-infected PBL cells. Upregulation in 2 of 4 breast tumor samples is sufficient to make a disease claim in cancer of the breast. Upregulation in 1 of 4 AD brain samples indicates a potential role in Alzheimer's disease. Downregulation in 3 of 3 COPD lung samples suggests involvement in chronic obstructive pulmonary disease. Upregulation in 1 of 4 asthmatic lung samples indicates a potential role for this gene in lung cancer. High expression in all of the immune cells. Also high to moderate expression in the OA and RA synovium samples, the OA bone samples, and in the chondrocytes suggests an involvement in osteoarthritis and rheumatoid arthritis. Gene Name sbgl02200MCTc Gene Name sbgl8525LRRb, SBhACRP30c, and sbgl23493SLITc Quantitative, tissue-specific, mRNA expression patterns of these three genes were measured using SYBR-Green Quantitative PCR (Applied Biosystems, Foster City, CA; see Schmittgen T.D. et al., Analytical Biochemistry 285:194-204, 2000) or TaqMan PCR (Perkin Elmer, see Lie et al. Current Opinion in Biotechnology 9:43-48, 1998; Gibson et al., Genome Methods 6:995-1001, 1996) and human cDNAs prepared from various human tissues. Gene-specific PCR primers were designed using the first nucleic acid sequence listed in the Sequence List for each gene. Results are presented as the number of copies of each specific gene's mRNA detected in lng mRNA pool from each tissue. Two replicate mRNA measurements were made from each tissue RNA. Table V. Additional diseases based on mRNA expression in specific tissues

Claims: What is claimed is: 1. An isolated polypeptide selected from the group consisting of: s (a) an isolated polypeptide encoded by a polynucleotide comprising a sequence set forth in Table I; (b) an isolated polypeptide comprising a polypeptide sequence set forth in Table I; and (c) a polypeptide sequence of a gene set forth in Table I. 2. An isolated polynucleotide selected from the group consisting of : (a) an isolated polynucleotide comprising a polynucleotide sequence set forth in Table I; (b) an isolated polynucleotide of a gene set forth in Table I; (c) an isolated polynucleotide comprising a polynucleotide sequence encoding a polypeptide set forth in Table I; (d) an isolated polynucleotide encoding a polypeptide set forth in Table I; (e) a polynucleotide which is an RNA equivalent ofthe polynucleotide of (a) to (d); or a polynucleotide sequence complementary to said isolated polynucleotide. 3. An expression vector comprising a polynucleotide capable of producing a polypeptide of claim 1 when said expression vector is present in a compatible host cell. 4. A process for producing a recombinant host cell which comprises the step of introducing an expression vector comprising a polynucleotide capable of producing a polypeptide of claim 1 into a cell such that the host cell, under appropriate culture conditions, produces said polypeptide. 5. A recombinant host cell produced by the process of claim 4. 6. A membrane of a recombinant host cell of claim 5 expressing said polypeptide. 7. A process for producing a polypeptide which comprises culturing a host cell of claim 5 under conditions sufficient for the production of said polypeptide and recovering said polypeptide from the culture.

Inventors: AGARWAL PANKAJ, BIRKELAND MARIAN, COGSWELL JOHN P, KABNICK KAREN F, LAI YING-TA, MARTENSEN SHELBY A, RIZVI SAFIA K, SMITH RANDALL F, STRUM JAY C, XIE QING, AGARWAL, PANKAJ, BIRKELAND, MARIAN, COGSWELL, JOHN, P., KABNICK, KAREN, F., LAI, YING-TA, MARTENSEN, SHELBY, A., RIZVI, SAFIA, K., SMITH, RANDALL, F., STRUM, JAY, C., XIE, QING
Applicants: AGARWAL PANKAJ, BIRKELAND MARIAN, COGSWELL JOHN P, GLAXO GROUP LTD, KABNICK KAREN F, LAI YING-TA, MARTENSEN SHELBY A, RIZVI SAFIA K, SMITH RANDALL F, SMITHKLINE BEECHAM CORP, SMITHKLINE BEECHAM PLC, STRUM JAY C, XIE QING, AGARWAL, PANKAJ, BIRKELAND, MARIAN, COGSWELL, JOHN, P., GLAXO GROUP LIMITED, KABNICK, KAREN, F., LAI, YING-TA, MARTENSEN, SHELBY, A., RIZVI, SAFIA, K., SMITH, RANDALL, F., SMITHKLINE BEECHAM CORPORATION, STRUM, JAY, C., XIE, QING
Application year: 2001
Main classification: C07K14
IPC codes: A61K38, A61K48, A61P9, A61P17, A61P25, A61P35, A61P37, C07K14, C12N1, C12N5, C12N15, C12P21