CA2395816A1 - Nucleic acids, proteins and antibodies - Google Patents

Nucleic acids, proteins and antibodies Download PDF

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CA2395816A1
CA2395816A1 CA002395816A CA2395816A CA2395816A1 CA 2395816 A1 CA2395816 A1 CA 2395816A1 CA 002395816 A CA002395816 A CA 002395816A CA 2395816 A CA2395816 A CA 2395816A CA 2395816 A1 CA2395816 A1 CA 2395816A1
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polypeptide
polynucleotide
cdna
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Craig A. Rosen
Steven C. Barash
Steven M. Ruben
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    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489Metalloendopeptidases (3.4.24)
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    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/05Animals comprising random inserted nucleic acids (transgenic)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/30Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00Screening for compounds of potential therapeutic value
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to novel proteins. More specifically, isolated nucleic acid molecules are provided encoding novel polypeptides. Novel polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human polynucleotides and/or polypeptides and antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to these novel polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.

Description

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NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME
NOTE POUR LE TOME / VOLUME NOTE:

Nucleic Acids, Proteins, and Antibodies [1] This application refers to a "Sequence Listing" that is provided only on electronic media in computer readable form pursuantto Administrative Instructions Section 801(a)(i).
The Sequence Listing forms a part of this description pursuant to Rule 5.2 and Administrative Instructions Sections 801 to 806, and is hereby incorporated in its entirety.
v [2] The Sequence Listing is provided as an electronic file (PTZ32PCT
seqList.txt, 3,411,276 bytes in size, created on January 13, 2001) on four identical compact discs (CD-R), labeled "COPY 1," "COPY 2," "COPY 3," and "CRF.". The Sequence Listing complies with Annex C of the Administrative Instructions, and may be viewed, for example, on an IBM-PC machine running the MS-Windows operating system by using the V viewer software, version 2000 (see World Wide Web URL: http://www.fileviewer.com).
Field of the Invention [3] The present invention relates to novel proteins. More speciftcally, isolated nucleic acid molecules are provided encoding novel polypeptides. Novel polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human polynucleotides and/or polypeptides, and antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to these novel polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention.
The present invention further relates to methods and/or compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.
Background of the Invention [4] One of the most critical tasks a cell must perform is to respond to cues from its environment, i.e., extracellular signals. Some of the most important extracellular signals come from other cells. The ability for cells to be able to send and receive signals from one another is of paramount importance in. multicellular organisms because it allows individual cells within a body to become highly specialized and yet work in a coordinated fashion with other cells of the body. Cellular signaling mechanisms regulate a variety of cellular processes such as, for example, proliferation, differentiation, survival, movement, and secretion. Defects in cellular signaling can lead to a number of diseases and disorders such as cancers, immune system disorders and nervous system disorders. For more expansive reviews on this subject, please refer to Hunter, Cell 100:113-127 and Chapter 15 of Molecular' Biology of the Cell, Third Edition, edited by Alberts et al.
(1994), which are herein incorporated by reference in their entirety.
[5] Signal transduction requires molecules that serve as the extracellular signaling molecules as well as a set of receptors that "receive" the signal. Frequently, an additional set of proteins is necessary in order for the cell to translate the signal it has received into an appropriate response via the activation or inhibition of a particular set of genes or proteins.
The signaling molecules, the receptor proteins, and the molecules that relay the signal between the receptor and the final effector molecules collectively form what are known as signal transduction pathways.
[6] To date, several common types of signal transduction pathways have been identified. One way to classify a signal transduction pathway is based on the class of receptor protein it utilizes. Two well known classes of receptor proteins are G-protein coupled receptors and enzyme-linked receptors. This latter class of enzyme-linked receptors includes receptor tyrosine kinases, tyrosine kinase associated receptors, receptor serine/threonine kinases, receptor tyrosine phosphatases, and receptor guanylyl cyclases.
Signal Ti~afzsduction th~ougla G protein Coupled Receptor s [7] G protein coupled receptors are the largest family of cell surface receptors. They are seven-pass transmembrane receptors which activate trimeric G proteins (G
proteins) upon ligand binding. G proteins are GTPases composed of three subunits: alpha, beta and gamma.
G proteins function as molecular switches existing in two states: an active GTP bound state and an inactive GDP bound state. Ligand binding to G protein coupled receptors induce inactive G proteins to release GDP allowing GTP to bind in its place. Binding of GTP to a G
protein causes the alpha subunit to dissociate from the beta and gamma subunits which remain associated with one another. Eventually, the GTPase activity of the alpha subunit results in hydrolysis of the bound GTP molecule to GDP, thus inactivating the G protein.
[8J There are several types of G proteins that have been classified based upon their function. Stimulatory G proteins (GS) are involved in adenylate cyclase activation; inhibitory G proteins (G;) function to inhibit the activity of adenylate cyclase. Yet another type of G
protein , Gq proteins, functions in the activation of phosphoinositide-specific phospholipase C
enzyme.
[9J Activation of adenylate cyclase by an activated GS protein results in the production of the cyclic nucleotide, cyclic AMP (cAMP). CAMP mediates its effects mostly through its activation of cAMP dependent kinase (A-kinase), a serine/threonine kinase.
Activation of A-kinase helps to further relay the signal from the G protein coupled receptor to the target proteins. In muscle cells, for instance, activation of A-kinase following adrenaline signaling ultimately results in the activation of an enzyme, glycogen phosphorylase, which catalyzes the release of glucose molecules which can be used to produce energy from glycogen. In other instances, activated A-lcinase translocates to the nucleus where it phosphorylates the CAMP response element binding (CREB) protein, which when phosphorylated, acts as a transcription factor to stimulate the expression of genes that have cAMP
response elements (CRE) sequences in their regulatory regions.
[10] Gq proteins, when activated, activate the enzyme phospholipase C-beta which hydrolyzes PI 4,5-biphosphate (PIP2) producing inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 functions as a second messenger that causes the release of Ca2+
from intracellular stores. Released calcium then binds to Ca2+ binding proteins such as calmodulin, which in its calcium bound state, is able to activate Ca2+/calmodulin dependent protein kinases (CaM-kinases). Activated CaM kinases then continue to relay the signal to more downstream molecules in the signal transduction pathway. The other product produced by phospholipase C-beta, DAG, functions to activate the serine/threonine lcinase known as protein kinase C (PKC). Activated PKC phosphoiylates target proteins depending on the cell type, and in many cells these phosphorylation events lead to the increased transcription of specific genes. The highest concentrations of protein kinase C are found in the brain where PKC phosphorylates ion channels in nerve cells thereby altering their excitability. PKC
activation can be induced by treating cells with phorbol esters which are able to cross the plasma membrane, bind to, and activate PKG directly. .
Signal Ts°afzsductiou through Receptor Tyrosine Kiraases [1l] The receptor protein tyrosine kinases (RPTKs) are some of the most well studied receptors, and the signaling cascades they initiate demonstrate two of the fundamental concepts in signal transduction: the regulation of protein phosphorylation and the recruitment of proteins into a signaling cascade via protein-protein interaction domains.
[12] Binding of the cognate ligand to a RPTK, such as epidermal growth factor (EGF) binding to the epidermal growth factor receptor (EGFR), induces RPTKs to dimerize and cross-phosphorylate each other on multiple tyrosine residues. The phosphorylated receptor dimer is the activated form of the receptor.
[13] The phosphorylated tyrosines on activated RPTKs are then recognized/bound by other components of the signal transduction pathway. One of the important discoveries in the field of signal transduction was the recognition of conserved domains which allow for protein-protein interactions in signaling pathways. The most prevalent binding domain that recognizes phosphotyrosine (P-Tyr) residues is known as the SH2 domain (for Src homology region 2, named after the Src protein in which the SH2 domain was first discovered).
Another domain that recognizes P-Tyr residues is called the P-Tyr binding domain (PTB).
The discovery of the SH2 domain was quickly followed by the discovery of several other protein-protein interaction domains involved in signal transduction and by the realization that most of these domains are modular in nature, meaning these domains fold independently - a most convenient feature for protein engineering. To date, more than 100 such protein interaction domains involved in signaling have been defined via comparative sequence analysis. Most of these domains recognize short linear sequences (approximately 4-10 amino acid residues in length), in some cases requiring phosphorylation of specific residues within the sequence allowing for inducible association. A convenient web based database, with links to abstracts of papers characterizing these domains can be found at http://smart.EMBL-Heidelberg.de.
[14] Proteins containing SH2 and PTB domains translocate to the plasma membrane where they associate with the activated RPTKs which, in turn, activates them through phosphorylation. By way of example, activation of the platelet derived growth factor receptor (PDGFR) results in the autophosphorylation of tyrosine residues in the cytoplasmic tail of the PDGFR. These P-Tyr residues then serve as the binding sites for other proteins, such as a GTPase (discussed in more detail below), phospholipase C-gamma, and the regulatory subunit of PI-3-kinase, Which are each able to recognize the P-Tyr residues in PDGFR via SH2 domains. The interaction of these proteins with the activated PDGFR
results in the translocation of these proteins to the plasma membranes where they have their substrates and the PDGFR mediated activation of these proteins via phosphorylation.
[15] In the previous example, each of the proteins recruited to the activated RPTK via their SH2 domains also had catalytic activities that allowed them to propagate a signal.
There are proteins involved in signal transduction, however, which have no ability in and of themselves to propagate a signal. Instead, these proteins, known as adaptor proteins, serve to couple activated RPTKs to other components of the signal transduction pathway which do have the capacity to propagate the signal. One such adaptor protein is known as Grb2. It contains one SH2 domain and two SH3 domains (another Src homology domain that mediates protein interactions). Grb 2 is constitutively associated with Sos protein, a guanine nucleotide releasing protein (GNRP), via its SH3 domain. Thus, when Grb2 associates with an activated receptor via its SH2 domain, it also brings Sos into proximity with the RPTK
which activates the Sos protein via phosphorylation.
[16] GNRP proteins, such as Sos, are one of two types of proteins that help regulate the activity of proteins belonging to the Ras superfamily of monomeric GTPases.
Ras proteins are proteins that are associated with the cytoplasmic side of the plasma membrane and help relay signals from RPTK to the nucleus to stimulate cell proliferation or differentiation. Ras proteins exist in two states, an inactive state in which ras is bound to GDP
and an active state in which ras is bound to GTP. Activated GNRP proteins promote the exchange of bound GDP for GTP on ras proteins, thereby activating ras. Ras, itself, is a GTPase that hydrolyzes GTP to GDP, and would therefore tend to inactivate itself over time. However, ras is an inefficient GTPase, so the inactivation of ras is enhanced by GTPase activating proteins (GAPS) which increase the rate of hydrolysis of GTP by ras.

[17] Activated Ras kinases then act to activate more downstream signaling events, including activation of the mitogen-activated protein kinase (MAPK) pathway which is a cascade of serine/threonine kinases. Ras binds to and activates a MAPK kinase kinase (MAPKKK, such as Raf 1, for example), which in turn activates a MAPK kinase (MAPKK) via phosphorylation, which in turn activates a MAPK. MAPKs relay signals downstream by phosphorylating various proteins in the cell including other kinases and/or regulatory proteins in the cell. For instance, an activated MAPK can enter the nucleus and help to initiate transcription of genes that must be expressed in order for the cell to respond to the extracellular signal, such as genes required for DNA replication in response to the extracellular proliferation signal.
[18] Another class of signaling receptors, receptor serine/threonine kinases (RSK) has recently been identified. An example of an RSK is the TGF-beta receptor.
Additionally, it has also been recently recognized that there are modular binding domains that recognize phosphoserine/phosphothreonine (P-Ser/P-Thr) residues. For instance, 14-3-3 domains recognize phosphoserines in specific amino acid contexts [RSX(P-Ser)XP] or [R(Y/F)X(P-Ser)XP) and may function in the assembly of signaling complexes. Other residues such as histidine and arginine can also be phosphorylated, and it is possible that additional kinases which phosphorylate these residues, or protein domains that bind phosphohistidine or phosphoarginine will be discovered.
Signaling hia Iht~acellula~ Receptor s [19] Some extracellular signals do not have cell surface receptors such as G
protein coupled receptors or receptor tyrosine kinases. Instead, these extracellular signals are able to traverse the plasma membrane and interact with their receptors in the cytoplasm. Examples of such signals are the steroid hormones and the gas nitrous oxide (NO). The steroid hormone receptors, once bound by their ligand, are generally able to translocate to the nucleus where they bind regulatory DNA elements that control the gene expression of specific genes. NO gas, on the other hand, generally enters a cell and reacts with iron in the active site of the enzyme guanylate cyclase, stimulating it to produce cyclic GMP (cGMP).
cGMP acts as a second messenger (similar to the way cAMP functions) and can stimulate further downstream signaling by binding to other proteins.

Te~~aiuatisag Signal Ti~ansductioya [20] As the effects of signal transduction are transient, there must also be mechanisms for terminating signal cascades. For example, G proteins are self inactivating, and there are a set of proteins, GAPS, that are devoted to increasing the rate of hydrolysis of bound GTP by ras proteins. Cyclic nucleotide second messngers such as cAMP and cGMP are hydrolyzed by phosphodiesterases. In the case of kinases, there generally exist a set of complementary phosphatases that function to dephosphorylate phosphorylated residues, thereby bringing the signaling event to a close.
Sigszal Ti~ansduction Pathway Componefzts and Disease [21] Because signal transduction is involved in the regulation of so many cellular processes, including proliferation, differentiation, survival, and apoptosis, it is not surprising that defects in cellular signal transduction pathway components lead to a number of diseases and disorders, especially cancers. For a review on Signal transduction pathway components and diseases, see Hunter, Philosophical Transactions of the Royal Society of London Series B 353:583-605 (1998) which is herein incorporated by reference in its entirety. For instance, approximately 30% of human cancers have mutations in a ras gene, and at least 18 tyrosine kinases have been identified as oncogenes in either acutely transforming retroviruses or in human tumors, such as for example, Src. And more than 95% of chronic myelogenous leukemias express an activated form of the c-Abl non-receptor tyrosine kinases.
[2Z] Mutations in signaling pathways are also implicated in a plethora of other diseases.
Mutation in Bruton's tyrosine kinase leads to X-linked agammaglobulinemia.
Inactivation of ZAP70 or JAK3 leads to a severe combined immunodeficiency disease. Coffin-Lowry syndrome occurs when the X-linked Rsk2 protein serine kinase gene is inactivated.
Myotonic dystrophy occurs when expression of the myotonic dystrophy serine kinase gene is decreased. Overexpression of the aurora2 serine kinase is implicated in colon carcinoma.
[23] The malfunction of signal transduction pathway components, particularly kinases, in diseases indicate that these genes are good targets for drugs/pharmaceuticals that either inhibit or activate their function. In fact, some such drugs have been developed and are already in use or in clinical trials. For instance, an inhibitor of cyclin dependent kinase 2 (cdk2), a kinase important in regulating cellular proliferation, is in clinical trials for cancer treatment, as are inhibitors of epidermal growth factor receptor tyrosine kinases and vascular endothelial growth factor receptor (VEGFR) tyrosine kinases. Inhibition of VEGFR activity reduces or eliminates the vascularization of tumors directed by VEGFR. An antagonistic monoclonal antibody, herceptin, against the erbB2 receptor tyrosine kinase is being used in breast cancer therapies to treat breast cancers where ErbB2 is overexpressed.
[24] Thus there exists a clear need for identifying and exploiting novel signal transduction pathway component polynucleotides and polypeptides. Although structurally related, such proteins may possess diverse and multifaceted functions in a variety of cell and tissue types. The inventive purified signal transduction pathway component polypeptides are research tools useful for the identification, characterization and purification of additional proteins involved in signal transduction. Furthermore, the identification of new signal transduction pathway component polynucleotides and polypeptides permits the development of a range of derivatives, agonists and antagonists at the nucleic acid and protein levels which in turn have applications in the treatment and diagnosis of a range of conditions such as, for example, cancer and other proliferative disorders (e.g., chronic myelogenous leukemia), immunological disorders (e.g., severe combined immunodeficiency and X-linked agammaglobulinemia), and nervous system disorders (Coffin-Lowry Syndrome), amongst other conditions.
Summary of the Invention [25] The present invention relates to novel proteins. More specifically, isolated nucleic acid molecules are provided encoding novel polypeptides. Novel polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human polynucleotides and/or polypeptides, and antibodies. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to these novel polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention.
The present invention further relates to methods and/or compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.
Detailed Description Tables [26J Table 1A summarizes some of the polynucleotides encompassed by the invention (including cDNA clones related to the sequences (Clone ID NO:Z), contig sequences (contig identifier (Contig ID:) and contig nucleotide sequence identifier (SEQ ID
NO:X)) and further summarizes certain characteristics of these polynucleotides and the polypeptides encoded thereby. The first column provides the gene number in the application for each clone identifier. The second column provides a unique clone identifier, "Clone ID
NO:Z", for a cDNA clone related to each contig sequence disclosed in Table 1A. The third column provides a unique contig identifier, "Contig ID:" for each of the contig sequences disclosed in Table IA. The fourth column provides the sequence identifier, "SEQ ID
NO:X", for each of the contig sequences disclosed in Table 1A. The fifth column, "ORF (From-To)", provides the location (i.e., nucleotide position numbers) within the polynucleotide sequence of SEQ ID NO:X that delineate the preferred open reading frame (ORF) that encodes the amino acid sequence shown in the sequence listing and referenced in Table 1A
as SEQ ID
NO:Y (column 6). Column 7 lists residues comprising predicted epitopes contained in the polypeptides encoded by each of the preferred ORFs (SEQ ID NO:Y).
Identification of potential immunogenic regions was performed according to the method of Jameson and Wolf (CABIOS, 4; 181-186 (1988)); specifically, the Genetics Computer Group (GCG) implementation of this algorithm, embodied in the program PEPTIDESTRUCTURE
(Wisconsin Package v10.0, Genetics Computer Group (GCG), Madison, Wisc.). This method returns a measure of the probability that a given residue is found on the surface of the protein.
Regions where the antigenic index score is greater than 0.9 over at least 6 amino acids are indicated in Table 1A as "Predicted Epitopes". In particular embodiments, polypeptides of the invention comprise, or alternatively consist of, one, two, three, four, five or more of the predicted epitopes described in Table 1A. It will be appreciated that depending on the analytical criteria used to predict antigenic determinants, the exact address of the determinant may vary slightly. Column 8, "Tissue Distribution" shows the expression profile of tissue, cells, and/or cell line libraries which express the polynucleotides of the invention. The first number in column 8 (preceding the colon), represents the tissue/cell source identifier code corresponding to the key provided in Table 4. Expression of these polynucleotides was not observed in the other tissues and/or cell libraries tested. For those identifier codes in which the first two letters are not "AR", the second number in column 8 (following the colon), represents the number of times a sequence corresponding to the reference polynucleotide sequence (e.g., SEQ ID NO:X) was identified in the tissue/cell source. Those tissue/cell source identifier codes in . which the first two letters are "AR" designate information generated using DNA array technology. Utilizing this technology, cDNAs were amplified by PCR and then transferred, in duplicate, onto the array. Gene expression was assayed through hybridization of first strand cDNA probes to the DNA array. cDNA probes were generated from total RNA extracted from a variety of different tissues and cell lines.
Probe synthesis was performed in the presence of 33P dCTP, using oligo(dT) to prime reverse transcription.
After hybridization, high stringency washing conditions were employed to remove non-specific hybrids from the array. The remaining signal, emanating from each gene target, was measured using a Phosphorimager. Gene expression was reported as Phosphor Stimulating Luminescence (PSL) which reflects the level of phosphor signal generated from the probe hybridized to each of the gene targets represented on the array. A local background signal subtraction was performed before the total signal generated from each array was used to normalize gene expression between the different hybridizations. The value presented after "[array code]:" represents the mean of the duplicate values, following background subtraction and probe normalization. One of skill in the art could routinely use this information to identify normal and/or diseased tissues) which show a predominant expression pattern of the corresponding polynucleotide of the invention or to identify polynucleotides which show predominant andlor specific tissue and/or cell expression. Column 9 provides the chromosomal location of polynucleotides corresponding to SEQ ID NO:X.
Chromosomal location was determined by finding exact matches to EST and cDNA sequences contained in the NCBI (National Center for Biotechnology Information) UniGene database.
Given a presumptive chromosomal location, disease locus association was determined by comparison with the Morbid Map, derived from Online Mendelian Inheritance in Man (Online Mendelian Inheritance in Man, OMIMTM. McKusick-Nathans Institute' for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD) 2000. World Wide Web URL:
http://www.ncbi.nlm.nih.gov/omim/). If the putative chromosomal location of the Query overlaps with the chromosomal location of a Morbid Map entry, an OMIM
identification number is disclosed in column 10 labeled "OMIM Disease References)". A key to the OMIM reference identification numbers is provided in Table 5.
[27] Table 1B summarizes additional polynucleotides encompassed by the invention (including cDNA clones related to the sequences (Clone ID NO:Z), contig sequences (contig identifier (Contig ID:) contig nucleotide sequence identifiers (SEQ ID NO:X)), and genomic sequences (SEQ ID NO:B). The first column provides a unique clone identifier, "Clone ID
NO:Z", for a cDNA clone related to each contig sequence. The second column provides the sequence identifier, "SEQ ID NO:X", for each contig sequence. The third column provides a unique contig identifier, "Contig ID:" for each contig sequence. The fourth column, provides a BAC identifier "BAC ID NO:A" for the BAC clone referenced in the corresponding row of the table. The fifth column provides the nucleotide sequence identifier, "SEQ
ID NO:B" for a fragment of the BAC clone identified in column four of the corresponding row of the table.
The sixth column, "Exon From-To", provides the location (i.e., nucleotide position numbers) within the polynucleotide sequence of SEQ ID NO:B which delineate certain polynucleotides of the invention that are also exemplary members of polynucleotide sequences that encode polypeptides of the invention (e.g., polypeptides containing amino acid sequences encoded by the polynucleotide sequences delineated in column six, and fragments and variants thereof).
[28] Table 2 summarizes homology and features of some of the polypeptides of the invention. The first column provides a unique clone identifier, "Clone ID
NO:Z", corresponding to a cDNA clone disclosed in Table 1A. The second column provides the unique contig identifier, "Contig ID:" corresponding to contigs in Table IA
and allowing for correlation with the information in Table 1A. The third column provides the sequence identifier, "SEQ ID NO:X", for the contig polynucleotide sequence. The fourth column provides the analysis method by which the homology/identity disclosed in the Table was determined. Comparisons were made between polypeptides encoded by the polynucleotides of the invention and either a non-redundant protein database (herein referred to as "NR"), or a database of protein families (herein referred to as "PFAM") as further described below.
The fifth column provides a description of the PFAM/NR hit having a significant.match to a polypeptide of the invention. Column six provides the accession number of the PFAM/NR
hit disclosed in the fifth column. Column seven, "Score/Percent Identity", provides a quality score or the percent identity, of the hit disclosed in columns five and six.
Columns 8 and 9, "NT From" and "NT To" respectively, delineate the polynucleotides in "SEQ ID
NO:X" that encode a polypeptide having a significant match to the PFAM/NR database as disclosed in the fifth and sixth columns. In specific embodiments polypeptides of the invention comprise, or alternatively consist of, an amino acid sequence encoded by a polynucleotide in SEQ ID
NO:X as delineated in columns 8 and 9, or fragments or variants thereof.
[29] Table 3 provides polynucleotide sequences that may be disclaimed according to certain embodiments of the invention. The first column provides a unique clone identifier, "Clone ID", for a cDNA clone related to contig sequences disclosed in Table 1A. ' The second column provides the sequence identifier, "SEQ ID NO:X", for contig sequences disclosed in Table 1A. The third column provides the unique contig identifier, "Contig ID:", for coritigs disclosed in Table 1A. The fourth column provides a unique integer 'a' where 'a' is any integer between 1 and the final nucleotide minus 15 of SEQ ID NO:X, and the fifth column provides a unique integer 'b' where 'b' is any integer between 15 and the final nucleotide of SEQ ID NO:X, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:X, and where b is greater than or equal to a + 14.
For each of the polynucleotides shown as SEQ ID NO:X, the uniquely defined integers can be substituted into the general formula of a-b, and used to describe polynucleotides which may be preferably excluded from the invention. In certain embodiments, preferably excluded from the invention are at least one, two, three, four, five, ten, or more of the polynucleotide sequences) having the accession numbers) disclosed in the sixth column of this Table (including for example, published sequence in connection with a particular BAC
clone). In further embodiments, preferably excluded from the invention are the specific polynucleotide sequences) contained in the clones corresponding to at least one, two, three, four, five, ten, or more of the available material having the accession numbers identified in the sixth column of this Table (including for example, the actual sequence contained in an identified BAC
clone).
[30] Table 4 provides a key to the tissue/cell source identifier code disclosed in Table 1A, column 8. Column 1 provides the tissue/cell source identifier code disclosed in Table 1A, Column 8. Columns 2-5 provide a description of the tissue or cell source.
Codes corresponding to diseased tissues are indicated in column 6 with the word "disease". The use of the word "disease" in column 6 is non-limiting. The tissue or cell source may be specific (e.g. a neoplasm), or may be disease-associated (e.g., a tissue sample from a normal portion of a diseased organ). Furthermore, tissues and/or cells lacking the "disease"
designation may still be derived from sources directly or indirectly involved in a disease state or disorder, and therefore may have a further utility in that disease state or disorder. In numerous cases where the tissue/cell source is a library, column 7 identifies the vector used to generate the library.
[31] Table 5 provides a key to the OMIM reference identification numbers disclosed in Table 1A, column 10. OMIM reference identification numbers (Column 1) were derived from Online Mendelian Inheritance in Man (Online Mendelian Inheritance in Man, OMIM.

McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine, (Bethesda, MD) 2000. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/).
Column 2 provides diseases associated with the cytologic band disclosed in Table 1A, column 9, as determined using the Morbid Map database.
[32] Table 6 summarizes ATCC Deposits, Deposit dates, and ATCC designation numbers of deposits made with the ATCC in connection with the present application.
[33] Table 7 shows the cDNA libraries sequenced, and ATCC designation numbers and vector information relating to these cDNA libraries.
[34] Table 8 provides a physical characterization of clones encompassed by the invention. The first column provides the unique clone identifier, "Clone ID
NO:Z", for certain cDNA clones of the invention, as described in Table 1A. The second column provides the size of the cDNA insert contained in the corresponding cDNA clone.
Definitions [35] The following definitions are provided to facilitate understanding of certain terms used throughout this specification.
[36] In the present invention, "isolated" refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered "by the hand of man" from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be "isolated" because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide. The term "isolated" does not refer to genomic or cDNA
libraries, whole cell total or mRNA preparations, genomic DNA preparations (including those separated by electrophoresis and transferred onto blots), sheared whole cell genomic DNA preparations or other compositions where the art demonstrates no distinguishing features of the polynucleotide/sequences of the present invention.
[37] As used herein, a "polynucleotide" refers to a molecule having a nucleic acid sequence encoding SEQ ID NO:Y or a fragment or variant thereof; a nucleic acid sequence contained in SEQ ID NO:X (as described in column. 3 of Table 1A) or the complement thereof; a cDNA sequence contained in Clone ID NO:Z (as described in column 2 of Table 1A and contained within a library deposited with the ATCC); a nucleotide sequence encoding the polypeptide encoded by a nucleotide sequence in SEQ ID NO:B as defined in column 6 of Table 1B or a fragment or variant thereof; or a nucleotide coding sequence in SEQ ID
NO:B as defined in column 6 of Table 1B or the complement thereof. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA
sequence, including the 5' and 3' untranslated sequences, the coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence. Moreover, as used herein, a "polypeptide" refers to a molecule having an amino acid sequence encoded by a polynucleotide of the invention as broadly defined (obviously excluding poly-Phenylalanine or poly-Lysine peptide sequences which result from translation of a polyA tail of a sequence corresponding to a cDNA).
[38] In the present invention, "SEQ ID NO:X" was often generated by ovexlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID NO:X is deposited at Human Genome Sciences, Inc.
(HGS) in a catalogued and archived library. As shown, for example, in column 2 of Table 1A, each clone is identified by a cDNA Clone ID (identifier generally referred to herein as Clone ID NO:Z). Each Clone ID is unique to an individual clone and the Clone ID is all the information needed to retrieve a given clone from the HGS library.
Furthermore, certain clones disclosed in this application have been deposited with the ATCC on October 5, 2000, having the ATCC designation numbers PTA 2574 and PTA 2575; and on January 5, 2001, having the depositor reference numbers TS-l, TS-2, AC-1, and AC-2. In addition to the individual cDNA clone deposits, most of the cDNA libraries from which the clones were derived were deposited at the American Type Culture Collection (hereinafter "ATCC").
Table 7 provides a list of the deposited cDNA libraries. One can use the Clone ID NO:Z to determine the library source by reference to Tables 6 and 7. Table 7 lists the deposited cDNA libraries by name and links each library to an ATCC Deposit. Library names contain four characters, for example, "HTWE." The name of a cDNA clone (Clone ID) isolated from that library begins with the same four characters, for example "HTWEP07". As mentioned below, Table 1A correlates the Clone ID names with SEQ ID NO:X. Thus, starting with an SEQ ID NO:X, one can use Tables 1, 6 and 7 to determine the corresponding Clone ID, which library it carne from and which ATCC deposit the library is contained in. Furthermore, it is possible to retrieve a given cDNA clone from the source Library by techniques known in the art and described elsewhere herein. The ATCC is located at 10801 University Boulevard, Manassas, Virginia 20110-2209, USA. The ATCC deposits were made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure.
[39] In specific embodiments, the polynucleotides of the invention are at least 15, at least 30, at least 50, at least 100, at least 125, at least 500, or at least 1000 continuous nucleotides but are less than or equal to 300 kb, 200 kb, 100 kb, 50 kb, 15 kb, 10 kb, 7.Skb, 5 kb, 2.5 kb, 2.0 kb, or 1 kb, in length. In a further embodiment, polynucleotides of the invention comprise a portion of the coding sequences, as disclosed herein, but do not comprise all or a portion of any intron. In another embodiment, the polynucleotides comprising coding sequences do not contain coding sequences of a genomic flanking gene (i.e., 5' or 3' to the gene of interest in the genome). In other embodiments, the polynucleotides of the invention do not contain the coding sequence of more than 1000, 500, 250, 100, 50, 25, 20, 15, 10, 5, 4, 3, 2, or 1 genomic flanking gene(s).
[40] A "polynucleotide" of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, or the complement thereof (e.g., the complement of any one, two, three, four, or more of the polynucleotide fragments described herein), the polynucleotide sequence delineated in columns 8 and 9 of Table 2 or the complement thereof, and/or cDNA sequences contained in Clone ID NO:Z (e.g., the complement of any one, two, three, four, or more of the polynucleotide fragments, or the cDNA clone within the pool of cDNA clones deposited with the ATCC, described herein), and/or the polynucleotide sequence delineated in column 6 of Table 1B or the complement thereof. "Stringent hybridization conditions"
refers to an overnight incubation at 42 degree C in a solution comprising 50% formamide, Sx SSC (750 mM NaCI, 75 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), Sx Denhardt's solution, 10% dextran sulfate, and 20 ~g/ml denatured, sheared salmon 'sperm DNA, followed by washing the filters in O.lx SSC at about 65 degree C.
[41] Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions. Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature. For example, lower stringency conditions include an overnight incubation at 37 degree C in a solution comprising 6X
SSPE (20X SSPE
= 3M NaCI; 0.2M NaHZP04; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 ug/ml salmon sperm blocking DNA; followed by washes at 50 degree C with 1XSSPE, 0.1%
SDS.

In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5X SSC).
[42] Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations.
The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
[43] Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide," since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone generated using oligo dT as a primer).
[44] The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. For example, polynucleotides can be composed of 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, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA 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 can be made to DNA and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms.
[45] The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which 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 can 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 in 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, for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods. Modifications include acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a hems 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 cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, 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);
POSTTRANSLATIONAL COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. 1-12 (1983); Seifter et al., Meth.
Enzymol. 182:626-646 (1990); Rattan et al., Ann. N.Y. Acad. Sci. 663:48-62 (1992)).
[46] "SEQ ID NO:X" refers to a polynucleotide sequence described, for example, in Tables lAor 2, while "SEQ ID NO:Y" refers to a polypeptide sequence described in column 6 of Table 1A. SEQ ID NO:X is identified by an integer specified in column 4 of Table 1A.
The polypeptide sequence SEQ ID NO:Y is a translated open reading frame (ORF) encoded by polynucleotide SEQ ID NO:X. "Clone ID NO:Z" refers to a cDNA clone described in column 2 of Table 1A.
[47] "A polypeptide having functional activity" refers to a polypeptide capable of displaying one or more known functional activities associated with a full-length (complete) protein. Such functional activities include, but are not limited to, biological activity, antigenicity [ability to bind (or compete with a polypeptide for binding) to an anti-polypeptide antibody, immunogenicity (ability to generate antibody which binds to a specific polypeptide of the invention), ability to form multimers with polypeptides of the invention, and ability to bind to a receptor or ligand for a polypeptide.
[48] The polypeptides of the invention can be assayed for functional activity (e.g.
biological activity) using or routinely modifying assays known in the art, as well as assays described herein. Specifically, one of skill in the art may routinely assay signal transduction pathway component polypeptides (including fragments and variants) of the invention for activity using assays as described in Examples 3 ~, 39, 49, 52-57, 64 and 67.
[49] "A polypeptide having biological activity" refers to a polypeptide exhibiting activity similar to, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold Iess activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention).
[50] Table 1A summarizes some of the polynucleotides encompassed by the invention (including contig sequences (SEQ ID NO:X) and clones (Clone ID NO:Z) and further summarizes certain characteristics of these polynucleotides and the polypeptides encoded thereby.

:-:

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O O p p O O O p O O O p O O O O O O O O O O O O O O
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[51] The first column in Table 1A provides the gene number in the application corresponding to the clone identifier. The second column in Table 1A provides a unique "Clone ID NO:Z" for a cDNA clone related to each contig sequence disclosed in Table 1A.
This clone ID references the cDNA clone which contains at least the 5' most sequence of the assembled contig and at least a portion of SEQ ID NO:X was determined by directly sequencing the referenced clone. The reference clone may have more sequence than described in the sequence listing or the clone may have less. In the vast majority of cases, however, the clone is believed to encode a full-length polypeptide. In the case where a clone is not full-length, a full-length cDNA can be obtained by methods described elsewhere herein.
[52] The third column in Table 1A provides a unique "Contig ID" identification for each contig sequence. The fourth column provides the "SEQ ID NO:" identifier for each of the contig polynucleotide sequences disclosed in Table 1A. The fifth column, "ORF (From-To)", provides the location (i.e., nucleotide position numbers) within the polynucleotide sequence "SEQ ID NO:X" that delineate the preferred open reading frame (ORF) shown in the sequence listing and referenced in Table 1A, column 6, as SEQ ID NO:Y.
Where the nucleotide position number "To" is lower than the nucleotide position number "From", the preferred ORF is the reverse complement of the referenced polynucleotide sequence.
[53] The sixth column in Table 1A provides the corresponding SEQ ID NO:Y for the polypeptide sequence encoded by the preferred ORF delineated in column 5. In one embodiment, the invention provides an amino acid sequence comprising, or alternatively consisting of, a polypeptide encoded by the portion of SEQ ID NO:X delineated by "ORF
(From-To)". Also provided are polynucleotides encoding such amino acid sequences and the complementary strand thereto.
[54] Column 7 in Table 1A lists residues comprising epitopes contained in the polypeptides encoded by the preferred ORF (SEQ ID NO:Y), as predicted using the algorithm of Jameson and Wolf, (1988) Comp. Appl. Biosci. 4:181-186. The Jameson-Wolf antigenic analysis was performed using the computer program PROTEAN (Version 3.11 for the Power Macintosh, DNASTAR, Inc., 1228 South Park Street Madison, WI). In specific embodiments, polypeptides of the invention comprise, or alternatively consist of, at least one, two, three, four, five or more of the predicted epitopes as described in Table 1A. It will be appreciated that depending on the analytical criteria used to predict antigenic determinants, the exact address of the determinant may vary slightly.

[55] Column 8 in Table 1A provides an expression profile and library code:
count for each of the contig sequences (SEQ ID NO:X) disclosed in Table 1A, which can routinely be combined with the information provided in Table 4 and used to determine the tissues, cells, and/or cell line libraries which predominantly express the polynucleotides of the invention.
The first number in column 8 (preceding the colon), represents the tissue/cell source identifier code corresponding to the code and description provided in Table 4.
For those identifier codes in which the first two letters are not "AR", the second number in column 8 (following the colon) represents the number of times a sequence corresponding to the reference polynucleotide sequence was identified in the tissue/cell source.
Those tissue/cell source identifier codes in which the first two letters axe "AR" designate information generated using DNA array technology. Utilizing this technology, cDNAs were amplified by PCR and then transferred, in duplicate, onto the array. Gene expression was assayed through hybridization of first strand cDNA probes to the DNA array. cDNA probes were generated from total RNA extracted from a variety of different tissues and cell lines.
Probe synthesis was performed in the presence of 33P dCTP, using oligo(dT) to prime reverse transcription.
After hybridization, high stringency washing conditions were employed to remove non-specific hybrids from the array. The remaining signal, emanating from each gene target, was measured using a Phosphorimager. Gene expression was reported as Phosphor Stimulating Luminescence (PSL) which reflects the level of phosphor signal generated from the probe hybridized to each of the gene targets represented on the array. A local background signal subtraction was performed before the total signal generated from each array was used to normalize gene expression between the different hybridizations. The value presented after "[array code]:" represents the mean of the duplicate values, following background subtraction and probe normalization. One of slcill in the art could routinely use this information to identify normal and/or diseased tissues) which show a predominant expression pattern of the corresponding polynucleotide of the invention or to identify polynucleotides which show predominant and/or specific tissue and/or cell expression.
[56] Column 9 in Table 1A provides a chromosomal map location for certain polynucleotides of the invention. Chromosomal location was determined by finding exact matches to EST and cDNA sequences contained in the NCBI (National Center for Biotechnology Information) UniGene database. Each sequence in the UniGene database is assigned to a "cluster"; all of the ESTs, cDNAs, and STSs in a cluster are believed to be derived from a single gene. Chromosomal mapping data is often available for one or more sequences) in a UniGene cluster; this data (if consistent) is then applied to the cluster as a whole. Thus, it is possible to infer the chromosomal location of a new polynucleotide sequence by determining its identity with a mapped UniGene cluster.
[57] A modified version of the computer program BLASTN (Altshul et al., J.
Mol.
Biol. 215:403-410 (1990); and Gish and States, Nat. Genet. 3:266-272 (1993)) was used to search the UniGene database for EST or cDNA sequences that contain exact or near-exact matches to a polynucleotide sequence of the invention (the 'Query'). A
sequence from the UniGene database (the 'Subject') was said to be an exact match if it contained a segment of 50 nucleotides in length such that 48 of those nucleotides were in the same order as found in the Query sequence. If all of the matches that met this criteria were in the same UniGene cluster, and mapping data was available for this cluster, it is indicated in Table 1A under the heading "Cytologic Band". Where a cluster had been further localized to a distinct cytologic band, that band is disclosed; where no banding information was available, but the gene had been localized to a single chromosome, the chromosome is disclosed.
[58] Once a presumptive chromosomal location was determined for a polynucleotide of the invention, an associated disease locus was identified by comparison with a database of diseases which have been experimentally associated with genetic loci. The database used was the Morbid Map, derived from OMIMTM (supra). If the putative chromosomal location of a polynucleotide of the invention (Query sequence) was associated with a disease in the Morbid Map database, an OMIM reference identification number was noted in column 10, Table 1A, labelled "OMIM Disease References)". Table 5 is a key to the OMIM
reference identification numbers (column 1), and provides a description of the associated disease in Column 2.

Clone ID SEQ ID CONTIG BAC ID: SEQ ID EXON
A

NO:Z NO:X ID: NO:B From-To H2CBH45 90 963811 AC068243 1279 . 1-309 i 971-1b91 HFKIT06 207 934019 AC026976 1,365 1-294 -HTEMU66 232 9444.19 AC006510 1384 1-1150 HTEMU66 232 9444.19 AC022305 1385 1-686 _ 933-996 ~HCESA79 319 912709 AC009065 1406 I-70 344.-1073 79'73-8858 HF'VHV40 349 945849 AC020911 1440 1-149 ss4-11 is HAPNZ77 359 887072 AC005859 1452 . 1-3893 [59] Table 1B summarizes additional polynucleotides encompassed by the invention (including cDNA clones related to the sequences (Clone ID NO:Z), contig sequences (contig identifier (Contig ID:) contig nucleotide sequence identifiers (SEQ ID NO:X)), and genomic sequences (SEQ ID NO:B). The first column provides a unique clone identifier, "Clone ID
NO:Z", for a cDNA clone related to each contig sequence. The second colmnn provides the sequence identifier, "SEQ ID NO:X", for each contig sequence. The third column provides a unique contig identifier, "Contig ID:" for each contig sequence. The fourth column, provides a BAC identifier "BAC ID NO:A" for the BAC clone referenced in the corresponding row of the table. The fifth column provides the nucleotide sequence identifier, "SEQ
ID NO:B" for a fragment of the BAC clone identified in column four of the corresponding row of the table.
The sixth column, "Exon From-To", provides the location (i.e., nucleotide position numbers) within the polynucleotide sequence of SEQ ID NO:B which delineate certain polynucleotides of the invention that are also exemplary members of polynucleotide sequences that encode polypeptides of the invention (e.g., polypeptides containing amino acid sequences encoded by the polynucleotide sequences delineated in column six, and fragments and variants thereof).

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x [60] Table 2 further characterizes certain encoded polypeptides of the invention, by providing the results of comparisons to protein and protein family databases.
The first column provides a unique clone identifier, "Clone ID NO:", corresponding to a cDNA clone disclosed in Table 1A. The second column provides the unique contig identifier, "Contig ID:" which allows correlation with the information in Table 1A. The third column provides the sequence identifier, "SEQ ID NO:", for the contig polynucleotide sequences. The fourth column provides the analysis method by which the homology/identity disclosed in the Table was determined. The fifth column provides a description of the PFAM/NR hit identified by each analysis. Column six provides the accession number of the PFAM/NR hit disclosed in the fifth column. Column seven, score/percent identity, provides a quality score or the percent identity, of the hit disclosed in column five. Comparisons were made between polypeptides encoded by polynucleotides of the invention and a non-redundant protein database (herein referred to as "NR"), or a database of protein families (herein referred to as "PFAM"), as described below.
[61] The NR database, which comprises the NBRF PIR database, the NCBI GenPept database, and the SIB SwissProt and TrEMBL databases, was made non-redundant using the computer program nrdb2 (Warren Gish, Washington University in Saint Louis).
Each of the polynucleotides shown in Table 1A, column 3 (e.g., SEQ ID NO:X or the 'Query' sequence) was used to search against the NR database. The computer program BLASTX was used to compare a 6-frame translation of the Query sequence to the NR database (for information about the BLASTX algorithm please see Altshul et al., J. Mol. Biol. 215:403-410 (1990);
and Gish and States, Nat. Genet. 3:266-272 (1993). A description of the sequence that is most similar to the Query sequence (the highest scoring 'Subject') is shown in column five of Table 2 and the database accession number for that sequence is provided in column six. The highest scoring 'Subject' is reported in Table 2 if (a) the estimated probability that the match occurred by chance alone is less than 1.0e-07, and (b) the match was not to a known repetitive element. BLASTX returns alignments of short polypeptide segments of the Query and Subject sequences which share a high degree of similarity; these segments are known as High-Scoring Segment Pairs or HSPs. Table 2 reports the degree of similarity between the Query and the Subject for each HSP as a percent identity in Column 7. The percent identity is determined by dividing the number of exact matches between the two aligned sequences in the HSP, dividing by the number of Query amino acids in the HSP and multiplying by 100.

The polynucleotides of SEQ ID NO:X which encode the polypeptide sequence that generates an HSP are delineated by columns 8 and 9 of Table 2.
[62] The PFAM database, PFAM version 2.1, (Sonnhammer et al., Nucl. Acids Res., 26:320-322, 1998)) consists of a series of multiple sequence alignments; one alignment for each protein family. Each multiple sequence alignment is converted into a probability model called a Hidden Markov Model, or HMM, that represents the position-specific variation among the sequences that make up the multiple sequence alignment (see, e.g., Durbin et al., Biological sequence analysis: probabilistic fnodels of proteins and nucleic acids, Cambridge University Press, 1998 for the theory of HMMs). The program HMMER version 1.8 (Sean Eddy, Washington University in Saint Louis) was used to compare the predicted protein sequence for each Query sequence (SEQ ID NO:Y in Table 1A) to each of the HMMs derived from PFAM version 2.1. A HMM derived from PFAM version 2.1 was said to be a significant match to a polypeptide of the invention if the score returned by HMMER 1.8 was greater than 0.8 times the HMMER 1.8 score obtained with the most distantly related known member of that protein family. The description of the PFAM family which shares a significant match with a polypeptide of the invention is listed in coltunn 5 of Table 2, and the database accession number of the PFAM hit is provided in column 6. Column 7 provides the score returned by HMMER version 1.8 for the alignment. Columns 8 and 9 delineate the polynucleotides of SEQ ID NO:X which encode the polypeptide sequence which show a significant match to a PFAM protein family.
[63] As mentioned, columns 8 and 9 in Table 2, "NT From" and "NT To", delineate the polynucleotides of "SEQ ID NO:X" that encode a polypeptide having a significant match to the PFAM/NR database as disclosed in the fifth column. In one embodiment, the invention provides a protein comprising, or alternatively consisting of, a polypeptide encoded by the polynucleotides of SEQ ID NO:X delineated in columns 8 and 9 of Table 2. Also provided are polynucleotides encoding such proteins, and the complementary strand thereto.
[64] The nucleotide sequence SEQ ID NO:X and the translated SEQ ID NO:Y are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, the nucleotide sequences of SEQ ID NO:X
are useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA contained in Clone ID NO:Z. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling immediate applications in chromosome mapping, linkage analysis, tissue identification and/or typing, and a variety of forensic and diagnostic methods of the invention. Similarly, polypeptides identified from SEQ ID NO:Y may be used to generate antibodies which bind specifically to these polypeptides, or fragments thereof, and/or to the polypeptides encoded by the cDNA
clones identified in, for example, Table 1A.
[65] Nevertheless, DNA sequences generated by sequencing reactions can contain sequencing errors. The errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence. The erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence. In these cases, the predicted amino acid sequence diverges from the actual amino acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases).
[66] Accordingly, for those applications requiring precision in the nucleotide sequence or the amino acid sequence, the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X, and a predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing cDNA
Clone ID
NO:Z (deposited with the ATCC on October 5, 2000, and receiving ATCC
designation numbers PTA 2574 and PTA 2575; deposited with the ATCC on January 5, 2001, and having depositor reference numbers TS-l, TS-2, AC-1, and AC-2; and/or as set forth, for example, in Table 1A, 6 and 7). The nucleotide sequence of each deposited clone can readily be determined by sequencing the deposited clone in accordance with known methods.
Further, techniques known in the art can be used to verify the nucleotide sequences of SEQ ID NO:X.
[67] The predicted amino acid sequence can then be verified from such deposits.
Moreover, the amino acid sequence of the protein encoded by a particular clone can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the protein, and determining its sequence.
RACE PYOtocol Fov Recovery of Full-Length Genes [68] Partial cDNA clones can be made full-length by utilizing the rapid amplification of cDNA ends (RACE) procedure described in Frohman, M.A., et al., Proc. Nat'l.
Aced. Sci.
USA, 85:8998-9002 (1988). A cDNA clone missing either the 5' or 3' end can be reconstructed to include the absent base pairs extending to the translational start or stop codon, respectively. In some cases, cDNAs are missing the start codon of translation, therefor. The following briefly describes a modification of this original 5' RACE procedure.
Poly A+ or total RNA is reverse transcribed with Superscript II (Gibco/BRL) and an antisense or complementary primer specific to the cDNA sequence. The primer is removed from the reaction with a Microcon Concentrator (Amicon). The first-strand cDNA
is then tailed with dATP and terminal deoxynucleotide transferase (GibcoBRL). Thus, an anchor sequence is produced which is needed for PCR amplification. The second strand is synthesized from the dA-tail in PCR buffer, Taq DNA polymerase (Perkin-Elmer Cetus), an oligo-dT primer containing three adjacent restriction sites (Xhol, SaII and CIaI) at the. 5' end and a primer containing just these restriction sites. This double-stranded cDNA is PCR
amplified for 40 cycles with the same primers as well as a nested cDNA-specific antisense primer. The PCR products are size-separated on an ethidium bromide-agarose gel and the region of gel containing cDNA products the predicted size of missing protein-coding DNA is removed, cDNA is purified from the agarose with the Magic PCR Prep kit (Promega), restriction digested with XhoI or SaII, and ligated to a plasmid such as pBluescript SKII
(Stratagene) at XhoI and EcoRV sites. This DNA is transformed into bacteria and the plasmid clones sequenced to identify the correct protein-coding inserts.
Correct 5' ends are confirmed by comparing this sequence with the putatively identified homologue and overlap with the partial cDNA clone. Similar methods known in the art and/or commercial kits are used to amplify and recover 3' ends.
[69] Several quality-controlled kits are commercially available for purchase.
Similar reagents and methods to those above are supplied in kit form from GibcoBRL for both 5' and 3' RACE for recovery of full length genes. A second kit is available from Clontech which is a modification of a related technique, SLIC (single-stranded ligation to single-stranded cDNA), developed by Dumas .et al.; Nucleic Acids Res., 19:5227-32 (1991). The major differences in procedure are that the RNA is alkaline hydrolyzed after reverse transcription and RNA ligase is used to join a restriction site-containing anchor primer to the first-strand cDNA. This obviates the necessity for the dA-tailing reaction which results in a polyT
stretch that is difficult to sequence past.
(70] An alternative to generating 5' or 3' cDNA from RNA is to use cDNA
library double-stranded DNA. An asymmetric PCR-amplified antisense cDNA strand is synthesized with an antisense cDNA-specific primer and a plasmid-anchored primer. These primers are removed and a symmetric PCR reaction is performed with a nested cDNA-specific antisense primer and the plasmid-anchored primer.

RNA Ligase Protocol For Generating The 5' or 3' End Sequences To Obtain Full Length Genes [71] Once a gene of interest is identified, several methods are available for the identification of the 5' or 3' portions of the gene which may not be present in the original cDNA plasmid. These methods include, but are not limited to, filter probing, clone enrichment using specific probes and protocols similar and identical to 5' and 3' RACE.
While the full length gene may be present in the library and can be identified by probing, a useful method for generating the 5' or 3' end is to use the existing sequence information from the original cDNA to generate the missing information. A method similar to. 5' RACE is available for generating the missing 5' end of a desired full-length gene.
(This method was published by Fromont-Racine et al., Nucleic Acids Res., 21(7):1683-1684 (1993)). Briefly, a specific RNA oligonucleotide is ligated to the 5' ends of a population of RNA
presumably containing full-length gene RNA transcript and a primer set containing a primer specific to the Iigated RNA oligonucleotide and a primer specific to a known sequence of the gene of interest, is used to PCR amplify the 5' portion of the desired full length gene which may then be sequenced and used to generate the full length gene. This method starts with total RNA
isolated from the desired source, poly A RNA may be used but is not a prerequisite for this procedure. The RNA preparation may then be treated with phosphatase if necessary to eliminate 5' phosphate groups on degraded or damaged RNA which may, interfere with the later RNA Iigase step, The phosphatase if used is then inactivated and the RNA
is treated with tobacco acid pyrophosphatase in order to remove the cap structure present at the 5' ends of messenger RNAs. This reaction leaves a 5' phosphate group at the 5' end of the cap cleaved RNA which can then be ligated to an RNA oligonucleotide using T4 RNA
ligase.
This modified RNA preparation can then be used as a template for first strand cDNA
synthesis using a gene specific oligonucleatide. The first strand synthesis reaction can then be used as a template for PCR amplification of the desired 5' end using a primer specific to the ligated RNA oligonucleotide and a primer specific to the known sequence of the gene of interest. The resultant product is then sequenced and analyzed to confirm that the 5' end sequence belongs to the relevant gene.
[72] The present invention also relates to vectors or plasmids which include such DNA
sequences, as well as the use of the DNA sequences. The material deposited with the ATCC
(deposited with the ATCC on October 5, 2000, and receiving ATCC designation numbers PTA 2574 and PTA 2575; deposited with the ATCC on January 5, 2001, and receiving ATCC designation numbers TS-l, TS-2, AC-1, and AC-2; and/or as set forth, for example, in Table 1A, Table 6, or Table 7) is a mixture of cDNA clones derived from a variety of human tissue and cloned in either a plasmid vector or a phage vector, as described, for example, in Table 7. These deposits are referred to as "the deposits" herein. The tissues from which some of the clones were derived are listed in Table 7, and the vector in which the corresponding cDNA is contained is also indicated in Table 7. The deposited material includes cDNA clones corresponding to SEQ ID NO:X described, for example, in Table 1A
(Clone ID NO:Z). A clone which is isolatable from the ATCC Deposits by use of a sequence listed as SEQ ID NO:X, may include the entire coding region of a human gene or in other cases such clone may include a substantial portion of the coding region of a human gene.
Furthermore, although the sequence listing may in some instances list only a portion of the DNA sequence in a clone included in the ATCC Deposits, it is well within the ability of one skilled in the art to sequence the DNA included in a clone contained in the ATCC Deposits by use of a sequence (or portion thereof) described in, for example Tables lAor 2 by procedures hereinafter further described, and others apparent to those skilled in the art.
[73] Also provided in Table 7 is the name of the vector which contains the cDNA
clone. Each vector is routinely used in the art. The following additional information is provided for convenience.
[74] Vectors Lambda Zap (U.S. Patent Nos. 5,128,256 and 5,286,636), Uni-Zap XR
(U.S. Patent Nos. 5,128, 256 and 5,286,636), Zap Express (U.S. Patent Nos.
5,128,256 and 5,286,636), pBluescript (pBS) (Short, J. M. et al., Nucleic Acids Res. 16:7583-7600 (1988);
Alting-Mees, M. A. and Short, J. M., Nucleic Acids Res. 17.9494 (1989)) and pBK (Alting-Mees, M. A. et al., Sty°ategies 5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, CA, 92037. pBS
contains an ampicillin resistance gene and pBK contains a neomycin resistance gene.
Phagemid pBS
may be excised from the Lambda Zap and Uni-Zap XR vectors, and phagemid pBK
may be excised from the Zap Express vector. Both phagemids may be transformed into E.
coli strain XL-1 Blue, also available from Stratagene.
[75] Vectors pSportl, pCMVSport 1.0, pCMVSport 2.0 and pCMVSport 3.0, were obtained from Life Technologies, Inc., P. O. Box 6009, Gaithersburg, MD 20897.
All Sport vectors contain an ampicillin resistance gene and may be transformed into E.
coli strain DH10B, also available from Life Technologies. See, for instance, Gruber, C.
E., et al., Focus 15:59- (1993). Vector lafmid BA (Bento Soares, Columbia University, New York, NY) contains an ampicillin resistance gene and can be transformed into E. coli strain XL-1 Blue.
Vector pCR~'2.1, which is available from Invitrogen, 1600 Faraday Avenue, Carlsbad, CA
92008, contains an ampicillin resistance gene and may be transformed into E.
coli strain DH10B, available from Life Technologies. See, for instance, Clark, J. M., Nuc.
Acids Res.
16:9677-9686 (1988) and Mead, D. et al., BiolTechfzology 9: (1991).
[76] The present invention also relates to the genes corresponding to SEQ ID
NO:X, SEQ ID NO:Y, and/or the deposited clone (Clone ID NO:Z). The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein.
Such methods include preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.
[77] Also provided in the present invention are allelic variants, orthologs, and/or species homologs. Procedures known in the art can be used to obtain full-length genes, allelic variants, splice variants, full-length coding portions, orthologs, and/or species homologs of genes corresponding to SEQ ID NO:X or the complement thereof, polypeptides encoded by genes corresponding to SEQ ID NO:X or the complement thereof, and/or the cDNA
contained in Clone ID NO:Z, using information from the sequences disclosed herein or the clones deposited with the ATCC. For example, allelic variants and/or species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for allelic variants and/or the desired homologue.
[78] The polypeptides of the invention can be prepared in any suitable manner.
Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art.
[79] The polypeptides may be in the form of the secreted protein, including the mature form, or may be a part of a larger protein, such as a fusion protein (see below). It is often advantageous to include an additional amino acid sequence which contains secretory or leader sequences, pro-sequences, sequences which aid in purification, such as multiple histidine residues, or an additional sequence for stability during recombinant production.

[80] The polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified. A recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified using techniques described herein or otherwise known in the art, such as, for example, by the one-step method described in Smith and Johnson, Gene 67:31-40 (1988). Polypeptides of the invention also can be purified from natural, synthetic or recombinant sources using.
techniques described herein or otherwise known in the art, such as, for example, antibodies of the invention raised against the polypeptides of the present invention in methods which are well known in the art.
[81] The present invention provides a polynucleotide comprising, or alternatively consisting of, the nucleic acid sequence of SEQ ID NO:X, and/or the cDNA
sequence contained in Clone ID NO:Z. The present invention also provides a polypeptide comprising, or alternatively, consisting of, the polypeptide sequence of SEQ ID NO:Y, a polypeptide encoded by SEQ ID NO:X or a complement thereof, a polypeptide encoded by the cDNA
contained in Clone ID NO:Z, and/or the polypeptide sequence encoded by a nucleotide sequence in SEQ ID NO:B as defined in column 6 of Table 1B. Polynucleotides encoding a polypeptide comprising, or alternatively consisting of the polypeptide sequence of SEQ ID
NO:Y, a polypeptide encoded by SEQ ID NO:X, a polypeptide encoded by the cDNA
contained in Clone ID NO:Z, and/or a polypeptide sequence encoded by a nucleotide sequence in SEQ ID NO:B as defined in column 6 of Table 1B are also encompassed by the invention. The present invention further encompasses a polynucleotide comprising, or alternatively consisting of, the complement of the nucleic acid sequence of SEQ ID NO:X, a nucleic acid sequence encoding a polypeptide encoded by the complement of the nucleic acid sequence of SEQ ID NO:X, and/or the cDNA contained in Clone ID NO:Z.
[82] Moreover, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in Table 1B column 6, or any combination thereof.
Additional, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the complementary strands) of the sequences delineated in Table 1B column 6, or any combination thereof. In further embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in Table 1B, column 6, and have a nucleic acid sequence which is different from that of the BAC fragment having the sequence disclosed in SEQ ID NO:B (see Table 1B, column 5). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in Table 1B, column 6, and have a nucleic acid sequence which is different from that published for the BAC'clone identified as BAC ID NO:A (see Table 1B, column 4). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in Table 1B, colunm 6, and have a nucleic acid sequence which is different from that contained in the BAC clone identified as BAC ID
NO:A (see Table 1B, column 4). Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides and polypeptides are also encompassed by the invention.
[83] Further, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in column 6 of Table 1B which correspond to the same Clone ID NO:Z
(see Table 1B, column 1), or any combination thereof. Additional, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the complementary strands) of the sequences delineated in column 6 of Table 1B which correspond to the same Clone ID NO:Z
(see Table 1B, column 1), or any combination thereof. In further embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in column 6 of Table 1B which correspond to the same Clone ID NO:Z (see Table 1B, column I) and have a nucleic acid sequence which is different from that of the BAC
fragment having the sequence disclosed in SEQ ID NO:B (see Table 1B, column 5). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in column 6 of Table 1B which correspond to the same Clone ID NO:Z (see Table 1B, column 1) and have a nucleic acid sequence which is different from that published for the BAC clone identified as BAC ID NO:A (see Table 1B, column 4). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in column 6 of Table 1B which correspond to the same Clone ID NO:Z (see Table 1B, column 1) and have a nucleic acid sequence which is different from that contained in the BAC clone identified as BAC ID
NO:A (see Table 1B, column 4). Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides and polypeptides are also encompassed by the invention.
[84j Further, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in column 6 of Table 1B which correspond to the same contig sequence identifer SEQ ID NO:X (see Table 1B, column 2), or any combination thereof.
Additional, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the complementary strands) of the sequences delineated in column 6 of Table 1B which correspond to the same contig sequence identifer SEQ ID NO:X (see Table 1B, column 2), or any combination thereof. In further embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in column 6 of Table 1B which correspond to the same contig sequence identifer SEQ ID NO:X (see Table 1B, column 2) and have a nucleic acid sequence which is different from that of the BAC
fragment having the sequence disclosed in SEQ ID NO:B (see Table 1B, column 5). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in column 6 of Table 1B which correspond to the same contig sequence identifer SEQ ID NO:X (see Table 1B, column 2) and have a nucleic acid sequence which is different from that published for the BAC clone identified as BAC ID NO:A (see Table IB, column 4). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in column 6 of Table 1B which correspond to the same contig sequence identifer SEQ ID NO:X
(see Table 1B, column 2) and have a nucleic acid sequence which is different from that contained in the BAC clone identified as BAC ID NO:A (See Table 1B, column 4).
Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides and polypeptides are also encompassed by the invention.
[85] Moreover, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in the same row of Table 1B column 6, or any combination thereof.
Additional, representative examples of polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the complementary strands) of the sequences delineated in the same row of Table 1B
column 6, or any combination thereof. In preferred embodiments, the polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the complementary strands) of the sequences delineated in the same row of Table 1B column 6, wherein sequentially delineated sequences in the table (i.e.
corresponding to those exons located closest to each other) are directly contiguous in a 5' to 3' orientation. In further embodiments, above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in the same row of Table 1B, column 6, and have a nucleic acid sequence which is different from that of the BAC fragment having the sequence disclosed in SEQ ID NO:B (see Table 1B, column 5). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in the same row of Table 1B, column 6, and have a nucleic acid sequence which is different from that published for the BAC clone identified as BAC ID
NO:A (see Table 1B, column 4). In additional embodiments, the above-described polynucleotides of the invention comprise, or alternatively consist of, sequences delineated in the same row of Table 1B, column 6, and have a nucleic acid sequence which is different from that contained in the BAC clone identified as BAC ID NO:A (see Table 1B, column 4).
Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
[86] In additional specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in column 6 of Table 1B, and the polynucleotide sequence of SEQ ID
NO:X (e.g., as defined in Table 1B, column 2) or fragments or variants thereof. Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
[87] In additional specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in column 6 of Table 1B which correspond to the same Clone ID NO:Z
(see Table 1B, column 1), and the polynucleotide sequence of SEQ ID NO:X
(e.g., as defined in Table 1A or 1B) or fragments or variants thereof. In preferred embodiments, the delineated sequences) and polynucleotide sequence of SEQ ID NO:X correspond to the same Clone ID NO:Z. Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
[88] In further specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, one, two, three, four, five, six, seven, eight, nine, ten, or more of the sequences delineated in the same row of column 6 of Table 1B, and the polynucleotide sequence of SEQ ID NO:X (e.g., as defined in Table 1A or 1B) or fragments or variants thereof. In preferred embodiments, the delineated sequences) and polynucleotide sequence of SEQ ID NO:X correspond to the same row of column 6 of Table 1B.
Polypeptides encoded by these polynucleotides, other polynucleotides that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
[89] In additional specific embodiments, polynucleotides of the invention comprise, or alternatively consist of a polynucleotide sequence in which the 3' 10 polynucleotides of one of the sequences delineated in column 6 of Table 1B and the 5' 10 polynucleotides of the sequence of SEQ ID NO:X are directly contiguous. Nucleic acids which hybridize to the complement of these 20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention.
Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids that encode these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.
[90] In additional specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, a polynucleotide sequence in which the 3' 10 polynucleotides of one of the sequences delineated in column 6 of Table 1B and the 5' 10 polynucleotides of a fragment or variant of the sequence of SEQ ID NO:X are directly contiguous Nucleic acids which hybridize to the complement of these 20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under Iower stringency conditions, are also encompassed by the invention. Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.

[91] In specific embodiments, polynucleotides of the invention ~ comprise, or alternatively consist of, a polynucleotide sequence in which the 3' 10 polynucleotides of the .
sequence of SEQ ID NO:X and the 5' 10 polynucleotides of the sequence of one of the sequences delineated in column 6 of Table IB are directly contiguous. Nucleic acids which hybridize to the complement of these.20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention. Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.
[92] In specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, a polynucleotide sequence in which the 3' 10 polynucleotides of a fragment or variant of the sequence of SEQ .ID NO:X and the 5' 10' polynucleotides of the sequence of one of the sequences delineated in column 6 of Table 1B are directly contiguous.
Nucleic acids which hybridize to the complement of these 20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention. Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention.
Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides, are also encompassed by the invention.
[93] In further specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, a polynucleotide sequence in which the 3' 10 polynucleotides of one of the sequences delineated in column 6 of Table 1B and the 5' 10 polynucleotides of another sequence in column 6 are directly contiguous. Nucleic acids which hybridize to the complement of these 20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention.
Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.

[94] In specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, a polynucleotide sequence in which the 3' 10 polynucleotides of one of the sequences delineated in column 6 of Table 1B and the 5' 10 polynucleotides of another sequence in column 6 corresponding to the same Clone ID NO:Z (see Table 1B, column 1) are directly contiguous. Nucleic acids which hybridize to the complement of these 20 lower stringency conditions, are also encompassed by the invention. Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.
[95] In specific embodiments, polynucleotides of the invention comprise, or alternatively consist of, a polynucleotide sequence in which the 3' 10 polynucleotides of one sequence in column 6 corresponding to the same contig sequence identifer SEQ
ID NO:X
(see Table 1B, column 2) are directly contiguous. Nucleic acids which hybridize to the complement of these 20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under lower stringency conditions, axe also encompassed by the invention.
Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.
[96] In specific embodiments, polynucleotides of the invention comprise, or alternatively consist of a polynucleotide sequence in which the 3' 10 polynucleotides of one of the sequences delineated in column 6 of Table IB and the 5' 10 polynucleotides of another sequence in column 6 corresponding to the same row are directly contiguous. In preferred embodiments, the 3' 10 polynucleotides of one of the sequences delineated in column 6 of Table 1B is directly contiguous with the 5' IO polynucleotides of the next sequential exon delineated in Table 1B, column 6. Nucleic acids which hybridize to the complement of these 20 contiguous polynucleotides under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention.
Polypeptides encoded by these polynucleotides and/or nucleic acids, other polynucleotides and/or nucleic acids encoding these polypeptides, and antibodies that bind these polypeptides are also encompassed by the invention. Additionally, fragments and variants of the above-described polynucleotides, nucleic acids, and polypeptides are also encompassed by the invention.
(97] Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. Accordingly, for each contig sequence (SEQ ID NO:X) listed in the fourth column of Table 1A, preferably excluded are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 and the final nucleotide minus 15 of SEQ ID
NO:X, b is an integer of 15 to the final nucleotide of SEQ ID NO:X, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:X, and where b is greater than or equal to a + 14. More specifically, preferably excluded are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a and b are integers as defined in columns 4 and 5, respectively, of Table 3. In specific embodiments, the polynucleotides of the invention do not consist of at least one, two, three, four, five, ten, or more of the specific polynucleotide sequences referenced by the Genbank Accession No. as disclosed in column 6 of Table 3 (including for example, published sequence in connection with a particular BAC clone). In further embodiments, preferably excluded from the invention are the specific polynucleotide sequences) contained in the clones corresponding to at least one, two, three, four, five, ten, or more of the available material having the accession numbers identified in the sixth column of this Table (including for example, the actual sequence contained in an identified BAC clone). In no way is this listing meant to encompass all of the sequences which may be excluded by the general formula, it is just a representative example. All references available through these accessions are hereby incorporated by reference in their entirety.

SEQ
ID EST Disclaimer lone NO: ontig Range ID X ID: of a ccession #'s NO: Z Range of b HBXCM38 15 9100861 - 2160 15 - AI752485, AI804792, AI439106, 2174 AI971133, AI991958, AI752484, AI432296, AI478420, AW082819, AI912373, 889026, AA894797, AI55416I, AI752414, HI3307, AI249I65, 861527, N62403, 889727, N47856, AI689339, AI368569, 861583, AI984780, AA219502, H44175, AI802627, AI752415, T32963, AW295386, AA985168, H06745, 840750, M79099, AA203312, 800511, A91842, A91846, A91844, and A91848.

HDPHI92 18 9099001 - 2933 15 - AC068341.

NEON 23 9307051 = 897 15 -HFCBB56 24 9100731 - 553 15 - AA339423, and AC068296.

HWBCE37 53 906968 1 - 418 15~-HDQDV69 56 937850 1 - 837 15 - AA887783, AW392670, U46341, 851 AL119457, AL119341, AW372827, U46346, AW384394, AW363220, AL119484, AL119497, AL119355, AL119319, AL119324, AL119443, 299396, U46350, U46351, AL119363, AL119391, AL119444, AL134902, U46347, U46349, AL119483, AL119396, AL134528, AL119418, AL119335, AL119496, AL119439, AL042433, AL119522, AL042965, AL134524, AL119399, AL134920, AL037205, AL119401, U46345, AL134536, AI142132, AL119464, AL042450, AL042614, AL043029, AL134525, AL134538, AI142131, AL042551, AL042984, AL042975, AL042544, AL043019, AL042970, AI142134, AL042542, AL043003, AL119488, AF169035, AF085233, AB026436, AR054110, A81671, AR066494, AR060234, and AR069079.

HFKDR14 58 974255 1 - 172115 - AI761729, AW162515, AW104395, AW298361, AI073443, N40162, AI832126, AI827518, AW297353, 852045, AI342317, 871958, AF128625, AF021936, and AB032950.

HIBBF63 75 912715 1 - 950 15 - AC012171, AC012171, AC012171, AC009065, AC009065, AC009065, AC005346, AC005346, and AC005346.

H2CBH45 90 963811 1 - 470 15 - AA307462, AA036880, AL133047, 484 D89677, AC068243, and AC068243.

HAMFM39 92 971347 1 - 459315 - AI951619, AI814592, AI745391, 4607 AI922346, AA426190, AW105735, AW297557, AI829867, AI971865, AA227834, AW028756, AA151872, AA757072, AI202419, AW 176248, AW295401, AI659079, AAI49658, AA425I59, AI765117, AI870033, AW194075, AA233413, AW102818, 861588, AA365664, AA365663, AA601170, 861532, AA357346, AA551861, AI66023I, AI467782, 299396, AW392670, AL119324, AL119319, U46350, U46351, AL119457, AL119484, AL119391, U46347, AW372827, AL119522, AL119439, AL119335, AW384394, AL119483, AW363220, AL119363, AL119497, U46349, AL119355, AL119444, AL119443, U46341, AL134518, AL134525, AL119341, AL037205, AL119401, U46346, AL119396, AL134538, AL134531, AL134528, AL119418, AL119496, AL119399, U46345, AL134524, AL042544, AL042614, AL042984, AL042542, AL043019, AL042450, AL134542, AL043003, AL042965, AL042975, AL043029, AL042551, AL119464, I05430, I05393, A10617, AR028792, AR028791, AR028793, I25027, AR054109, I44515, I26928, I26930, I26927, I25041, I44516, A01324, AR035224, AR009151, I85513, AR009152, A01323, AR027099, AR034783, A94046, A94054, I63120, AR067733, AR064322, AR064323, AR064320, AR064321, A32110, A94048, A94061, A49045, AR038321, A83642, AR019094, A83643, A70359, A92666, AR038307, A92668, A92667, I49890, A92665, A92081, A92080, A92077, A92078, A92079, AR018924, AR018923, A48774, A48775, AR000006, AR015960, AR015961, AR000007, A91752, A91751, AR051652, A85308, AR068508, AR068510, AR068509, I91969, A91754, I58322, I58323, AR003585, A63067, A51047, A63064, A63072, AR031375, AR068507, A60213, AR068506, AR062871, A44171, AR068550, A23373, AR068551, A49700, A60207, A60208, A29109, A32111, I58669, A58521, AR031374, I07209, I07249, A63954, AR051651, AR019097, AR019098, AR019096, AR029417, I77227, AR020199, AR020200, AR001287, AR020198, AR020197, I89986, AR051957, AR029418, AR067734, AR067731, AR067732, Y14971, A93444, A46342, A46343, AB026436, I09121, AR032878, AR060234, AR066494, A81671, AR054110, and AR069079.

HBGQT03 93 9081731 - 1196 15 - AW193981, AA576536, AW439879, AA218860, AA587394, AI735027, AW206358, AI075695, AI749755, AI073515, AI283940, AI828816, AW328242, AA452508, AI741698, F25077, AA454093, AI280249, AI826261, AI567379, AA350150, AI251129, F26225, AI354257, AA171893, AW129660, AI357160, F26293, F36700, H24638, AI270014, AI952189, AA834233, AI689497, AI688448, F17480, 238509, T11668, N93072, AW362737, T11669, AW273866, N93071, AW328241, AF130979, AC024045, AC024045, and AC024045.

HBIBQ89 95 9097821 - 851 15 - AA399613, F11248, 242117, 865 AA082253, F05395, T35421, and AB007925.

HCECM90 96 9450881 - 1379 15 - AA463356, AA453500, AA322899, AA340682, H24259, AA603868, AA330182, 819782, and AB023227.

HCEPH71 97 5227391 - 432 15 - AA326209, AA383931, AL365319, 446 and ' AL390715.

HCOOZl 100 9653061 - 689 15 - AI350354, AI904299, AI902503, l 703 D61534, T78554, AW 183962, AI218626, AW304978, W74167, AI081779, AL022238, AL137499, AL022238, AL022238, and AL022238.

HCWFF88 101 5065771 - 304 15 - AL157951, AL157951, AL157951, 318 and AC025670.

HDMAVOl 102 11946961 - 1796 15 -HDPDA47 103 9291931 - 1036 15 - AW402583, AL049683, and AL023653.

HDPFF24 104 9092321 - 447 15 - AI929099, AI566117, AI928828, 461 N88094~

AA365879, AA281290, H67457, N87549, AW450464, AA295368, AA527887, AI033615, AA354369, AA086081, and AA903373.

HDPP035 105 9662481 - 1890 15 - AI640500, AW439548, AI823872, ~ 1904 AW297416, AA831672, AI815031, AA994323, AA741162, AA471280, AI223999, AW339548, AW235171, AI635436, AA035703, AA747998, AI371399, N67227, AA361754, AA063573, AI536057, AI357169, 833401, C01451, 833402, AA825399, AF165138, and AF130247.

HDTKQ14 107 8869361 - 541 15 - AL023653, AL049683, AL359542, AL359542, and AL359542.

HE8PK12 I09 9098841 - 707 15 - AA296029, AL117472, U58883, 721 AF136380, AF136381, AF078667, and AF078666.

HE9SE62 110 9114761 - 915 15 - AW021430, AI765247, AI822051, 929 AI822104, AA010459, N70537, AL133567, and AB018312.

HFBDJ13 112 9112641 - 476 15 - M86084, and AF030131.

HFTDF15 113 6570201 - 367 15 - AL365277, AL365277, AL365277, AC024511, AC024511, and AC024511.

HHE ' 114 9328511 - 873 15 - AA355773, and AA355926.

HHFCK09 115 9653041 - 2789 15 - AI218626, AI076006, AW 162820, 2803 AI797880, AI922744, AI872391, AI559566, AL045117, AW161046, AW162613, AI565503, AW183962, AI857802, AA460810, AI$84907, AI371131, AW248493, AI081779, AA460372, AA679085, N27884, AA581796, AA074070, AA971563, AI292006, AI922373, W76538, N93245, AI609183, AW172513, AI904299, AI682939, AA075764, AI885613, AA747871, AA449042, AA928020, AW401847, AA449757, AW268637, AW073851, AW304978, AI683858, AA568598, W74167, AI367698, AW19I998, N62781, AW016535, AI902503, AA347639, AA297591, AA379280, AA568887, AA649970, AW264577, AI221886, H20460, AW387087, AW000860, AI275195, AA341002, T32918, AW162711, W25103, AI699657, 842681, AW243790, AA768740, T78554, AI279653, AI560482, AI696251, AI951374, 245830, AA147203, AI499410, 843259, AI350354, AA732831, AW079129, AA375228, F08622, AI475009, 856337, AA379846, 817163, AW380349, AA783050, AW247402, N47545, 835508, 851077, AI474934, N79729, D61534, 241466, AI678630, AA339343, AW367003, AA160401, 241592, AW079321, N47546, AI252528, 858857, T16943, H55297, AL022238, AL137499, and AJ236700.

HISDS62 116 9359321 - 506 15 - W27339, AA126I05, AA306119, 520 W27700, AB007884, and AJ250425.

HLQDT35 117 8397771 - 516 15 - AA706241, AA707183, AA152440, 530 N99172, AA131985, AA358765, AA253107, 810421, _ N56752, AA290907, 808557, AA485099, AI091625, AA134742, AL137699, AC010998, AC010998, AC010998, AC013357, AC013357, and AC013357.

HLWFN63 118 9084371 - 3089 15 - AA707313, AI880426, AI684827, 3103 AI744551, AI307796, AA101249, AI284152, AA007399, N98643, AI375268, N66095, 871685, 802817, AA085724, AI221876, AI061056, AW207571, AA111956, AI460369, AI333887, AA594062, 818624, 862793, W22434, AW007868, AA776586, T70023, 871720, H70803, AA323135, AA101290, AA029721, AA320669, AI193496, 807828, AA007478, AI915644, AI932703, T69946, 862792, AA029660, AI859215, AA205667, AI625446, AI273982, AB018333, AC006599, AL033378, AL033378, AC006599, and AC006599.

HMSCD15 120 9181331 - 1223 15 - AA828277, AI707568, AI333720, 1237 W33154, AI880870, AA848014, AA864599, N50622, AW087770, AW270419, AA761244, AA262754, AA779760, AI880826, AW407353, W37119, AA206843, 242584, AA206842, AB011126, AL158207, AL158207, and AC027008.

HMTAW83 122 911385 1 - 487 15 - AI908321, AA831896, AR058970, 501 AR058968, A68194, and AR058969.

HMVAM09 123 963814 1 - 100915 - AI685410, AI969804, AA621392, 1023 AA358533, AW135812, AI376856, and AI276887.

HNSAA28 124 946988 1 - 154415 - AA713959, AI564093, AA768779, AA825697, AA808021, AA808149, AI401490, AW 181992, AW444640, AI018I59, AF146277, and AF077003.

HOUFT36 127 911293 1 - 832 15 - AI806483, AI147946, AA256164, 846 AW236751, AA057615, AW362445, AA542823, AF162130, AC005084, and AF161181.

HPMFL08 128 959569 1 - 452 15 - AA555286, AA640814, AI281916, AW073979, AI378363, 870468, AW242350, AW013856, AA644290, AW449140, 293016, AC012384, AL035541, AC005228, AC003662, AC009300, and 293016.

HRSMD49 129 723025 1 - 443 15 - AA136820.

HSDII69 130 917180 1 - 161215 - AA203346, AA203330, AA489694, AI912487, AW024848, AA133454, AA640288, AA658936, 224863, AA665267, AA878769, AI024792, AI383978, AW022618, T31809, AA318980, T86474, AA669824, AA115749, AW296909, AA552781, AI459513, AI332862, AI332863, and T86475.

HSDSB06 131 949151 1 - 226415 - AW009631, AI765056, AA877550, AA102362, AA625117, AA447454, AA446651, AA724535, AI220147, AA430607, AA019158, AI198643, AW389353, AA516463, AW197881, AA045561, AA186967, H86071, AW378928, H12433, AA768085, 866487;

AA478635, N55248, AA359925, 833870, AA385529, AA054621, AA961423, AW002948, AI802284, AA377365, D31590, AW275740, AI766068, C01179, AL133047, D89677, and AF003234.

HTEAG49 135 954614 1 - 128915 - AW452652, AI039005, AA780077, AW316890, AI337290, AA463229, AA463230, AI423317, AI468158, AA382497, N66986, AF041822, AL390796, AL390796, AL357045, and AL357045.

HTLBH67 136 751985 1 - 432 15 - W 19592, AC005368, AC008439, 446 AC022420, AC022420, AC022420, AC005368, AC005368, AC008781, and AC008781.

HTLJC71 137 922923 1 - 173815 - AL039539, AL045443, AI336919, 1752 AA406128, AA405229, AL042307, AA431504, AA311249, AW086440, AA813520, AI240644, AA897733, AW268487, AA782009, AW172455, AI301209, AI014598, AA969918, AL041043, AA431178, AL039540, AA973051, AI221826, AL133030, AC009516, AP000552, AP000556, AP000557, AL117509, AC023490, AC023490, AC009516, AC009516, AC009516, AC018752, AC018751, AC018751, AC007957, and AC007957.

HTPAD46 138 5033131 - 343 15 - AA386091, AA386130, AL133510, 357 and AC010932.

HTTKP07 139 9113901 - 562 15 - AI640500, AA035703, AF130247, 576 and AF165138.

HUCOW 140 9333571 - 843 15 - W52616, AA102287, 860274, 17 857 AA307147, H17000, H15631, C03464, and AA192581.

HWHGF52 141 7261021 - 441 15 - AA223889, and AB002360.

HWMBM1 144 9096831 - 858 15 - AI339104, AA861042, AA134985, 3 872 AA868144, AA134946, AI626100, AA922724, AA535447, AA056635, AA308766, D25742, AA916634, AA551763, AA873574, AW192836, AR044148, AL158847, and AL158847.

HWWDN3 145 9113571 - 1233 15 - AI671062, AI023330, AW243448, 4 1247 AI990947, AW081367, AW391909, AA448391, AI984688, AA448394, AI283270, AI344135, AW014216, AA127530, AA335984, AA377148, 242084, 812430, AA400585, AC019214, and AC019214.

HFKL,A09148 11788001 - 2072 15 -HDPVY89 156 8270261 - 684 15 - AC026283, and AC026283.

HODAK55 159 I l 1 - 713 15 -HAMGXlS 165 11779321 - 750 15 -HFOXK14 180 603245 1 - 616 15 - AL096870, and AL096870.

HHFLU06 182 857884 1 - 316 15 - AL096870 and AL096870.

HAGBA56 183 732597 1 - 653 15 - AA812064, AA430303, AA430200, AI803142, AI425013, AA954361, AB020641, U62391, AF033655, AC006036, AC000057, and AC002458.

HAGGF84 184 911312 1 - 421 15 - AL135568, AJ252239, AF071569, 435 U73504, D14906, J05072, X63615, AC004056, and AC004168.

HAHGD33 185 921782 1 - 105115 - AW378448, AW378426, AA064738, 1065 243369, AA984486, D31100, W79308, T35774, T08259, W52734, W73106, AI904952, 810018, AA348984, T80752, AA639598, 857404, T81225, AW408302, T81300, 813945, T47464, W79389, 243504, AA404490, AA196613, W01185, H14918, H45144, and AF113249.

HAHIY08 186 962113 1 - 265 15 - AA100160, AA307684, AA244505, 279 857782, AA864846, AR044133, and AR044123.

HBIOZ10 187 973131 1 - 490 15 - AC010761, and AC010761.

HBKDI30 188 729048 1 - 625 15 - AA197072, 802824, J05194, 639 J03886, and AL160175.

HBXBW40 189 706115 1 - 462 15 - AL023754, AL049688, and D86557.

HCEHE35 190 909937 1 - 378 15 - AB019692.

HCEPW85 191 911374 1 - 302 15 - N83965, AA326737, and H14153.

HCFAT25 192 932068 1 - 579 15 - AI287912, AL134532, AF096300, 593 AB014587, AC005035, AL137755, and U88984.

HDAAV61 194 810305 1 - 329 15 - AI762433, AI191825, AA159268, 343 AA083866, AW105372, AA157878, AI140935, AI922109, AA158846, AA488548, AI187149, AA442140, AA837990, AI494201, AL048644, AI366974, AI537837, AA425228, AW410089, AL038605, AI821259, AW084097, AW083168, AI624304, AI918554, AA508692, AI918634, AI307494, AI349622, AI738867, AI310571, AI802372, AI918408, AW021662, AI348897, AI366959, AW058233, AI345397, AL038564, AW089275, AI340511, AA857847, AI446405, AI799305, AW022494, AW020288, AI28I867, AI312210, AI307569, AI270295, N71180, AI702301, N75771, AL036652, AW021373, AL036856, AI312428, AI866820, AW059713, AI889147, N27632, AI336513, AW022102, AA019646, AI348895, AI313320, AI336495, AI310920, AI307503, AW079736, AW082532, AW089572, AI345143, AI309391, AI955906, AI309431, AI336662, AI868204, AI310575, AI349276, AI307507, N22406, AA420722, AI336565, AI683559, AL040694, AI311440, AI334893, AI349186, AI340533, AW088560, AI690472, AI521005, AI537515, AI493601, AI348847, AW083572, AW020397, AA493923, AI521799, AA835966, AI334895, AI309380, AW068845, AA814721, AI343091, AI401697, AA176980, AI815232, AW020419, AI340627, AW087838, AA555145, AI366968, AI348969, AI625464, AI307210, AW022636, AI348854, AI584130, AI679959, AI313352, AA789133, AW268072, AI336585, AI349787, AI349266, AI334452, N99092, AI312271, AI345114, AI344938, AI305745, AI345224, AW 168503, AA127565, AI312146, AI590423, AI312339, AI340537, AI500659, AI345258, AW054972, AA848053, AI307459, AI559863, AI349971, AI348879, W33163, AW193134, H89138, AW090539, AI348777, AI311604, AI343030, AI311892, AI680377, AI349805, AI887775, AI582871, AI349814, AI310930, AI500706, AI335426, AW263804, AI312333, AW268261, AI349957, AI345370, AI114703, AI370392, AI500662, AA460184, AI783861, AW150487, AI310945, AI336634, AI889168, AI440263, AI307735, AI345471, AI963690, AI312431, AI468959, T99953, AI345005, AI613343, AI571699, AW162189, AI312353, AI271234, AI623736, AI888956, AI560545, AI934000, AI343131, AI540606, AI334884, AI307543, AI567582, AI345251, AI349269, AW071412, AI254226, AW020592, AI307734, AI859644, AI307708, AI804505, AW058279, AI582912, AW172723, N29277, AI312325, AW071395, AI345156, AI242736, AI340659, AW071377, AI311159, AI866573, AI672130, AA579232, AI343140, AI452556, AI612885, AI340644, AI636788, AA837508, AI440091, AI572396, AA494167, AI702065, AI334930, AI309443, AI862066, AI345562, AI702527, 841605, AI307520, AW020693, AI371228, AI345026, AI679174, AI805688, AC007136, Y11092, AL137565, AF125532, AF003737, E01314, J05032, I48978, AF111851, L30117, X65873, AL133014, AL137560, X93495, A08913, AR038854, I89947, A08912, A08910, I89931, A08909, 577771, AL050015, I89934, AF162270, I49625, A08908, 576508, D83989, A18777, A08907, AF113676, A27171, AL137641, U75932, AF067728, AB007812, L13297, AL050146, X63574, AF017437, D89079, U57715, AL133098, AF120268, AL133010, E12579, AF061943, I00734, 561953, X79812, E00617, E00717, E00778, U72620, A08911, AF114818, AL122045, AL080074, AL137658, E15324, AL080140, AL050108, AF113013, M30514, AF078844, AF113690, E02253, 272491, AF106697, M27260, AF151109, AF205861, AJ010277, A52563, AL137548, AF055917, AR011880, E15569, AF095901, AF042090, AL110159, I89944, L31397, AR034830, I96214, AL110197, AF125948, AL137558, U49434, AL080129, AF012536, AF143957, U42031, AL117440, A08915, AL080060, AF113019, S36676, Y10080, U00763, AF153205, AF094480, AF017790, AF026124, AF017152, AF058921, X06146, AL133077, AF158248, AL137656, A12297, A08916, AF008439, AC004093, AL137539, Y10655, 575997, AF113694, AJ001838, X76228, Y10823, Y11254, A83556, AF00030I, AR059883, X54971, AL049466, AF016271, AL050393, AL049452, E12580, X53587, X57961, AP000081, AR068466, AF026816, I48979, AL110171, AL080086, X63410, AR020905, AF091084, AB016226, AL133067, AF126247, AF113677, AF175903, A07588, AF118094, AL049464, AF097996, L40363, U90884, U53505, AF176651, AL137459, U55017, AJ238278, AL117460, U95114, L31396, X99717, AL122093, U42766, AL137521, AL137479, X96540, AL110280, X72889, A58524, X00861, A58523, AC002467, AC006371, I29004, AL080124, AB019565, AL133104, AL133637, AFl 10329, AL049938, AL137557, AL133558, X62580, X70685, AR029490, AL049314, AF106827, AL133081, I42402, I46765, AL137648, AF031147, E01812, AF079763, AL117585, U68233, I92592, E07108, A07647, AF036268, 568736, AL117394, U72621, AL133565, AL133031, AL133606, AJ006417, AF061573, X98834, AL122123, AL031346, AC004227, Y08769, I22272, AL137463, AF169154, L19437, AR059958, AL122098, AF061795, AF151685, U57352, X66975, AF139986, AL050092, AF137367, X98066, AL122049, AF113689, 563521, AF118064, AB026995, AF118070, AL050277, AF113699, U58996, AF159615, AL137711, AL080162, AF125949, U62966, AL137547, X67813, AC007136, AC007136, and AC007136.

HDPKD75 195 8108241 - 524 15 - AA923698, AL040000, AF191838, AR016417, AF191839, and AF145705.

HDPNC96 196 9345201 - 720 15 - AA256100, and AB023182.

HDPSR15 197 9696661 - 1218 15 - AW195239, AW149418, AW005579, AI378013, AA147800, AI436586, AI392913, AW337924, AI377235, AI26493I, AI203549, AW 104319, AI094031, AA461376, H59980, AW166255, AA508841, AI360737, AA463275, AA417605, AI682196, H59937, AI208175, N30324, AA460078, AW001677, AA514325, N50317, AA741518, AI091790, T11446, AA360254, AI208678, AA214523, D20738, 861563, T12550, T11445, AA428834, AI276889, AB026289, and AR044150.

HDQDX20 198 9190271 - 1280 15 - AI905612, N75655, N94726, 1294 AA297704, H53438, AW339945, AW405560, AA719945, AI682436, AA971968, AW085268, H67340, AI419590, AI863597, 884229, AA996342, H69541, D45315, AI002247, AI138274, AI648605, W03933, AA348656, AI610448, AI769304, AA362755, AI708290, D45320, AW270686, AF169035, AF085233, and AF 113007.

HDTBY88 200 9344721 - 495 15 - AA868305, AI700890, AA789239, 509 AI803004, AI694352, AA043382, F08474, 821498, AF112183,AF112184, andAC005354.

HE2KZ07 201 9099481 - 1167 15 - AI141657, AW410635, AI377644, 1181 AI373441, AI435842, AI813994, AI222162, AI816276, AA134062, AA11552I, AA027340, AI198968, AI936995, AA432023, AI417110, AA019881, AA431770, T33003, AI804202, AW296590, AA894568, AA888588, AI816392, AW 157195, AA774185, AI312197, AA770240, AI005469, T15996, AI589559, T83662, AI802351, AA164900, AI637808, AW294821, AI612103, AI452706, 896447, AI214546, AA083117, AI219844, AI312448, AA978205, H98210, AI423512, AA115526, N74543, AI823785, H19250, T16797, AI803155, AW051574, 241102, AI300274, AA970855, T30646, T78862, T81921, 842142, 838428, 805531, T99321, H16697, 808035, AA114950, H52123, AA114923, 841504, 808085, F18392, D79266, 842920, AI028740, AAl 14993, F34433, F25527, AA130289, C02151, AL118820, AI696123, H10371, AA954386, T34819, AA135800, AI219437, T81018, AA135799, AI372829, AI056831, H68913, AW051694, AI986390, W28788, H10372, U95740, D86556, AB004267, AB023027, and AF181984.

HE8UY74 202 9609141 - 553 15 - N23547, H06088, 224919, 894366, AA010516, AA004981, AA304780, AL356968, and AL356968.

HE9N066 203 9743531 - 976 15 - AI732997, AA865818, AA977633, 990 269734, AB035267, AB020741, and 268339.

HEMBT61 204 9399571 - 449 15 - N86549, AW369713, and AB002301.

HETLF29 205 9097621 - 404 15 - AA960957, AI001155, and AC004664.

HFIUE75 206 9097581 - 1104 15 - AA745592, AA780791, AI680317, AA205127, 806019, AW074511, T76970, AW408392, T86065, T77135, AI709216, 805922, T85884, AA730855, and 877022.

HFHIT06 207 9340191 - 286 15 - AC026976, AC068353, AC068353, AF284563, AF284563, and AC026976.

HHEGG20 208 8944091 - 808 15 - AF084205.

HHEHC53 209 9217831 - 896 15 - AW408302, AW410815, AW 161181, AA160313, AA226860, AA044358, AI632654, AA232389, 243369, AA249020, T35774, AA852244, AA064738, AA295773, D31100, 813945, AA205277, T47464, T08259, AI904952, AF113249, AC009427, AC009427, and AC009427.

HHERQ79 210 9440571 - 497 15 - AW340333, AI806295, AW268810, AA827664, AA829237, AA909185, AA919008, AA604425, AW407893, AA011359, AL134902, D63485, AB016590, AB016589, and AR043113.

HISAF59 211 959140 1 - 899 15 - AW401787, AI394630, AI418298, AW375742, T30407, 244281, F07299, 825015, T32685, AA974700, F07734, AA297059, AW239548, AA897415, 845025, AI807678, AI343378, AW206793, AW138409, AW163027, AI815476, AA503315, AA047793, AW137324, AW140018, AI936871, AI015047, AI017077, AI168175, AI302185, AI025217, F03423, 846686, AI073417, 240806, AA026054, AW002416, AI652375, F03562, T03397, AI983297, H42881, T82311, AI025310, AI831833, 808769, AI911100, AA471062, AW157059, AA382959, H22172, AI356604, AI537006, AI825970, AW338394, AW192088, AI559159, AA593826, AW078709, and 261277.

HKAKM10 212 918685 1 - 596 15 - AW166113, 888730, AF071071, 610 AF170303, AF170304, AF077658, and AF071070.

HLTHP86 213 919354 1 - 247015 - AA702160, AI457618, AI951809, 2484 AI808761, AI911971, AI808636, AI633963, AI092909, AA922021, N53I71, AA809486, AI092910, AI253245, AA236950, AI432182, AI093897, AI363415, N50448, AI248799, AA663589, AA235935, AI239417, AA121162, AW270053, AI889821, AW296666, AI263508, N50504, H16878, H09671, AW028355, AW300355, 856761, H84971, AI373750, H16267, 244040, 244727, AI025923, N58608, T95750, T34716, AA363673, 843831, AA687486, 891239, AI829631, AA687431, AA852910, H16769, T95749, AI268135, AI686257, 856913, 240554, AA834548, AA872305, C02338, and AF 161420.

HMSJL96 214 934483 1 - 662 15 - 801798.

HMTAJ73 215 813296 1 - 651 15 - AI831613, AI924408, AI870169, 665 AW068406, AI368905, AW168626, AI284115, AA678670, AA568895, H19069, AA627558, AA857431, AJ010119, AF074714, AF074715, AC015698, and AC015698.

HNTCP13 216 909770 1 - 179315 - AI479379, AW273740, AA463847, 1807 AI740675, AI014722, AI922082, AA463334, AW009462, AI073540, N95224, AI190238, AA007373, AI798079, AA476563, AA670286, H02882, N92851, AA652716, AW016339, H45475, W25554, AA774170, H45576, AI370125, AI811794, AW119159, H03781, H20952, AA853882, AA853883, AI471060, AW382128, AW371996, W21053, H20991, AA368628, AW138258, AA476448, AA876335, AA788825, AF037447, and AC004486.

HNTMD79 217 934522 1 - 573 15 - AA305176, AL160291, AL160291, AL365228, and AL365228.

4~i4~

HNTMH70 218 7571841 - 674 15 - H19102, AI699883, AI383263, 688 AC005726, and AC004807.

HNTNB14 219 9099421 - 644 15 - AA082976, 860839, AA349498, 658 F12661, T74243, L22557, AC068701, and AC068701.

HODFF88 220 9749111 - 1843 15 - D80164, D59502, D80193, D80195, 1857 D59275, C15076, D80227, D58283, D80022, D80166,"

D81030, D59859, D51799, D59619, D80210, D80391, D80240, D59787, D51423, D80253, D80043, D80269, D50979, D80212, D80038, D80196, D80024, D80219, D80188, C14331, D59467, D57483, D59927, D80378, D80366, C14389, D59889, D50995, D80045, D59610, AA305409, C14429, D80241, D51060, T03269, C14014, AW178893, C75259, AA305578, D81026, D59695, D51022, AW179328, D81111, AW178775, D80134, AW378532, AW177440, D51250, AW352158, D80268, F13647, AA514188, AW369651, D80251, D80522, D51079, D80248, D80949, D58253, AW178762, D80168, D52291, C14227, AA514186, AI905856, AW177501, AW177511, D80133, 221582, AW360811, C05695, C14298, AW352117, D80064, AW176467, AW375405, AW378540, C14407, AW377671, D51097, AW366296, D80302, AW360844, AW360817, AW375406, AW378534, AW179332, AW377672, AW179023, AW178905, D80132, AW360834, AA285331, D80439, AW352171, AW377676, AW178906, AW352170, AW177731, D80247, AW178907, AW179019, AW179024, D51103, AW 177505, AW360841, AW 179020, AW 178909, AW 177456, AW
179329, AW178980, AW177733, AW378528, AW 178908, AW 178754, AW
179018, AW179220, AI557751, AW179004, AW178914, AW378525, AW352174, T11417, D80157, AW 177728, D59627, D51759, AW367967, AW'178774, AW178911, AW378543, AW352163, D59503, D80258, D80014, C06015, AI557774, AW178983, AW352120, T03116, AW178781, T48593, D58246, C14077, D59653, AW177723, D58101, D45260, AI525923, AW178986, AW367950, C03092, AA809122, H67854, D59551, H67866, C14975, T02974, AW378533, AW378539, D51213, AW177734, AI535686, D59317, D51221, AI525917, C14973, AA514184, C14344, D45273, AI525925, AI525920, D59474, AI525227, D31458, C14046, AI525242, AI525235, T03048, AI525912, AW378542, AI525215, AI525237, C16955, C05763, 233452, AI535850, AI535961, A84916, AJ132110, A62300, A62298, AR018138, X67155, Y17188, D26022, A25909, A67220, D89785, A78862, D34614, D88547, AF058696, X82626, AR008278, AB028859, AR025207, I82448, Y12724, A82595, AB012117, AR060385, AB002449, A85396, AR066482, A44171, A85477, A94995, X68127, I19525, A86792, X93549, AR008443, AR016808, U87250, I50133, I50126, I50132, I50128, AR066488, AR016514, AR060138, A45456, A26615, AR052274, I14842, Y09669, A43192, A43190, AR038669, AR066487, A30438, AF135125, D88507, AR066490, D50010, AR054175, I18367, Y17187, A63261, AR008277, AR008281, AR008408, AR062872, A70867, AB033121, AR016691, AR016690, U46128, D13509, AR060133, I79511, AR064240, A64136, A68321, U87247, AB023656, U79457, AF123263, ' X93535, and AR008382.

HPCRV84 222 945856 1 - 475 15 - AA307070, D79997, L76158, 489 and X95351.

HRACK83 223 888037 1 - 566 15 - AC005832.

HRADM45 224 717358 1 - 468 15 - AA418916, AA426580, AJ271722, 482 AP000260, AP000036, AF055919, AP000099, and AP000098.

HRAED74 225 942527 1 - 691 15 - AC005940, L42810, 583194, 705 AF117384, and AB023658.

HRODZ70 226 942673 1 - 572 15 - AA292911, AA167655, AA167766, 586 H97685, AA635138, 241812, and AB007941.

HSKAC24 227 823869 1 - 498 15 - AF170301, AF170302, AF077659, 512 and AF 144573.

HSSMT34 228 911294 1 - 540 15 - AA378627, F07835, and AL117482.

HT3BG12 229 921593 1 - 368 15 - AB028951, and AL122055.

HTEG005 230 932583 1 - 108615 - AA059465, AA059211, AA731209, AA236961, T86500, T87461, AL024498, and M35862.

HTEKT33 231 953308 1 - 164815 - AW292935, AW027321, AW027332, AI538521, AL040176, H29877, H85389, H29974, H84772, 241499, AL045794, T24112, T24119, D80253, D80043, AI744745, AL039924, D80219, AW013814, D59275, T10477, D51250, D80240, AA016312, D80227, H00069, D80210, D51423, D80134, AL043441, T02921, D59619, D80193, AL039156, D80391, AL039150, AL043445, AL038821, D59787, AL039509, AL039564, AL039538, AL044530, AL039108, AL039678, D80196, AL039074, AL038837, AL039625, AL039648, AL039629, AL039566, D80045, AL039659, T23947, AL037726, AL038531, D80168, AL039109, AL040992, AL039128, AL044407, AL036973, AL043423, AL045337, AL037051, AL045353, AL036725, AL039386, AL039423, AL045341, AL042909, AL039410, C14227, D80366, AL043422, AL038025, D59927, T11051, D81026, AL039085, AL036196, C14014, D59889, AI535783, AW451070, D80038, C75259, D50995, C15076, AL037639, 847228, D80022, AI535983, AL037526, AL037615, D80I95, D80949 D58283, D81030, D51799, T11417, D80188, D80378, D80522, D59467, F13647, AW452756, AI.036767, T03269, T23659, AL036117, D50979, D80212, D59502, D52291, 221582, AA285331, D80164, C14429, D80166, D59859, D80269, D59695, AL036765, AI557751, D80268, AL036924, AA514190, AL038851, D58253, T48598, C14298, D80024, AL036191, D57483, D59610, AL037679, AL036418, D80241, D59627, D81111, AI910186, C14389, C14331, 225782, AL037601, AL036679, D51060, AL036238, AW178893, AA305409, AL037047, D51079, AL037082, AW177440, D51022, AW179328, AW178775, AA305578, D80014, AW378532, AI557774, AW352158, AI905856, AW377671, D51213, AW369651, D80251, AA514188, D51097, AL036964, D80248, AW178762, AW177501, AW177511, D80064, AW360834, 299396, AA514186, D80133, AW360811, AW352117, T02974, C05695, AL037054, H00072, C14407, AW176467, AW378540, AW375405, D80302, AL036733, AL037021, AW366296, AW360844, AW360817, AW375406, AW378534, AW179332, D80132, AW377672, AW179023, AW178905, AW179220, AL036158, D80439, AW352171, D59373, AW377676, D80258, AW178906, AW352170, AW177731, D80247, AW 178907, AW 179019, AW
179024, AW378539, AW177505, C14077, AW450376, AW 179020, AW360841, C06015, AW 178909, AW 177456, AW 179329, AW
178980, AW 177733, AW378528, AW 178908, AW178754, AW179018, A85396, A25909, AR025207, X68127, A86792, A44171, A85477, U87250, A67220, AR062871, A84772, AR067732, A84776, AR017907, I18371, A84773, A84775, AR037157, A84774, AR062872, AR062873, AR067731, A20702, A58522, A43189, A43188, A20700, A91750, D34614, AR043602, AR043603, AR043601, AR036905, AJ244003, AR018924, A95051, AR018923, A48774, A98767, A48775, A38214, A95117, AR015960, A95052, A93963, A93964, I63120, I56772, 195540, AR000007, AR015961, A18053, AR031374, A63067, A51047, A63064, A49700, AR031375, A63072, A23334, A75888, I70384, A18050, AR068507, AR068506, A601~11, A23633, AR007512, A23998, I03343, A58521, AR020969, I06859, A58524, I60241, I60242, AR054109, E12615, AR022240, AR035193, A58523, A92133, A24783, A24782, A81878, A27396, AR027100, I28266, E14304, A97211, A49045, AF156294, A82653, AF156296, E16636, A58525, A64081, I25027, E16678, I26929, I44515, I26928, AB012117, I26930, I26927, A93016, I49890, AR038762, AR000006, I44516, E13740, A58526, A91753, 296142, AR066482, Y17188, I68636, V00745, AJ244004, A02712, X73004, E16590, AR008430, I19516, D88984, I03665, I03664, A15078, A10361, AR036903, AJ244005, D28584, A35537, A02136, A04664, Y11923, A13393, A35536, A02135, A04663, A11245, A02710, I13349, A07700, A13392, I19517, I01992, A76773, A22413, I21869, A70040, AF118808, I08051, I00074, I92483, AR038286, E00523, A97221, E03165, E02221, E01614, E13364, I00079, D26022, A92636, Y11926, I66495, I66494, I66498, I66497, I66496, I66486, I66487, AJ230933, I19525, E06034, I00077, A51384, AR035975, AR035974, AR035977, AR035976, AR035978, 570644, D14548, I25041, I07429, A62300, A91754, A62298, 565373, A60957, X58217, AF019720, X67155, A60968, A84916, X13220, I84554, I69350, I84553, A04710, AR027069, AF096793, AJ132110, A20701, A52326, X92518, D44443, AF096810, 578798, A10363, A60985, A60990, A78862, AB007195, A60987, D89785, X15418, E04616, A18722, A80951, I08250, 569292, AF130655, M32676, AR018138, D88547, X93549, X82626, I07888, AF058696, AR008278, AB028859, 583538, AF135125, I82448, and I15997.

HTEMU66 232 9444191 - 107815 - 1092AL039924, AL045794, AW013814, AL036630, T02921, AL044412, T24119, AL044364, T24112, AW450335, AL039476, D51250, D80253, D80043, AL040992, AL039109, AL038531, AL037726, AL039629, AL039625, AL039648, -AL038837, AL039074, AL039678, AL039108, AL039538, AL039564, AL039156, AL039659, AL039566, AL039509, AL039521, H00069, AL039128, AL044407, AL036973, AL045337, AL037051, AL045353, AL039386, AL039423, AL045341, AL042909, AL039410, D59787, AL039150, AL044530, AL038821, AL038025, D80219, AL036725, AL043422, D59275, AL043445, AL039459, AI535983, D80227, AL043586, AL043423, D80240, AL043441, D80210, D51423, T23947, AL036650, D80134, AL036196, D59619, D80391, AL037639, D80193, AW451070, AL037615, D80196, AL036767, C14227, AL039085, AI535783, D80949, AL036117, D80366, D59927, AL037526, AL042334, AW452756, D80168, 847228, AL036238, AL036679, AL037601, T11051, D81026, AL039504, C14014, D50995, C75259, AL039842, AL036964, D80045, AL036733, AL036158, AL037027, AL036924, AL037054, D59889, AL036765, T23659, AI557751, AL038851, T23658, AL037177, AL036998, D80022, AL037047, AL044413, AW293068, AL037643, AL036227, AL036418, AL036133, D80038, T11417, AL037082, AL036163, D58283, D80195, AL036207, AL037124, D81030, D80188, AL037021, AL036191, AL036167, AL036132, AL037049, AL037679, AL036190, AL037600, D51799, AL036139, D80378, F13647, D80522, T03269, AL036152, T23656, C14429, T48598, D50979, D80212, AL036900, 221582, AL037178, AA514190, AL048425, AA285331, AW451416, D59502, AL043613, D58253, AL039555, AL043585, D80166, D59859, AL037085, D80268, D80269, 225782, AL037569, D80024, D52291, 614331, AL036174, AL036808, AL036953, D57483, 299396, D59610, AW450376, AL044178, D80241, AL036150, D8111 l, AI910186, D80164, D59627, C14389, H00072, C15076, D59467, D51060, AA305409, AL036268, AW178893, D51213, D51079, C14298, AL038043, N47620, D80251, AW177440, D51022, C14407, AL044447, AW179328, D80014, AW178775, AL037077, AW378532, AA305578, D80064, AW352158, D80248, D59695, AI905856, AW369651, D51097, AL043840, AL037002, AW178762, AA514188, AW177501, AWI77511, AA514186, D80133, AW360834, AL039417, AW360811, C05695, 225783, AI557774, AW135155, D80258, T02974, AW352117, AW176467, AW375405, AW378540, AW377671, AA809122, AW366296, A25909, A85396, A86792, A44171, A85477, X68127, AR062871, A84772, A84776, A84773, A84775, A84774, AR037157, AR017907, AR062872, AR062873, AR067731, AR067732, A58522, A91750, A20702, A43189, A43188, A20700, AR036905, A95051, AR038762, A95117, A38214, A98767, AR031374, I56772, I95540, AR018924, A49700, A63067, A51047, A63064, AR018923, A48774, A63072, A95052, A48775, AR068507, AI8053, AR068506, A93963, A93964, A23334, A75888, I70384, AR043602, AR015960, AR043603, AR043601, A5852I, AR000007, AR015961, A18050, A60111, A23633, A10361, A23998, AR007512, AR020969, I60241, I60242, I63120, AR054109, I03343, AR031375, AR022240, A58524, A58523, A81878, A24783, A24782, E12615, AR035193, A92133, E14304, A27396, AR027100, I28266, A49045, E16678, A82653, E16636, I06859, A93016, I25027, AR000006, I26929, E13740, I44515, I26928, I26930, I26927, A58525, I49890, I44516, A58526, A91753, AJ244003, AR025207, I18371, E06034, AF156296, A13038, A29289, AR029417, AF156294, AR067733, AR029418, AR067734, A64081, AR028669, AR028668, AR028667, AR028670, AR017908, A68112, A68104, A98467, I62368, AR031488, I13521, I52048, I44531, A84746, A17115, AR028672, A18079, AR038066, I50882, I15353, I66495, I66494, I66498, I66497, I66496, I66486, I66487, A71440, A71435, A67220, I13349, A07699, E08322, I74623, A60109, AJ244004, U87250, I00081, A70040, AR028564, A83643, A98420, A98423, A98432, A98436, A98417, A98427, A83151, I01968, A13388, E00974, A02228, E00954, E00952, E00953, E00955, I08049, I43960, AR021440, E03165, E02221, E13364, A10360, E02679, E02104, E02098, A92666, E02001, E01718, E02003, E02102, E03550, A28163, E02100, E01997, A58998, E02291, E02292, E02293, E01999, E02396, E02327, E01563, E02431, E01693, E01696, A92668, AR005163, AR005154, AR005157, AR005160, I09250, AR005153, A92667, E01024, AR050583, AR050584, E02430, E01148, E12527, E01503, AR005165, E12523, E02432, A49701, A62009, E01216, I77211, A95096, I70974, I31847, I31848, AR060673, AR060676, A95106, A95105, A80476, A91965, E01324, I08638, A80474, A94048, A94061, A80477, AR035224, A80475, A94046, A94054, I63560, AR031529, A49428, I63561, I63563, E16036, AC018903, AC068470, AL049186, AL049186, AC006S 10, AL022167, and AC022305.

HTEMV09 233 909843 1 - 13471S - AI818734, AA454060, AA453640, AW268879, AI377304, AI818733, AI818743, AI681535, AI741915, AA948041, AI198872, AW341578, AI267885, AA767746, AI677678, AI829855, AI677729, AW 129267, AA947425, AA297313, AL041049, N67346, and AA889773.

HTLEJ11 236 973302 1 - 956 15 - M62294.

HTOAK34 238 966800 1 - 127115 - AW408167, AA491322, AA505126, AI340133, AA831203, N27153, AA053564, AA809481, AF181985, and AF179867.

HTPGG25 239 911282 1 - 829 15 - AA018361, AI768326, AI333117, 843 AA324901, F07835, AA378627, AL117482, 261430, AC020705, and AC020705.

HUTSF11 241 966029 1 - 416 15 - AI384010, AI288640, 220435, 430 and A74523.

HWAFG04 244 952878 1 - 164615 - AI302185, AI652375, AI936871, 1660 AW206793, AI025217, AI983297, AW002416, AI025310, AA593826, AI559159, AI418298, AW140018, AI017077, D54154, T03397, AW239548, H42947, D57560, AW192088, 823870, AI394630, AA503315, AA026054, F07734, 240806, AI807678, AA297059, C14980, AW338394, AI073417, AW 138409, AA088799, AI356604, C15480, AI825970, AI537006, AI168175, 846685, AA974700, AW078709, 846686, AI343378, AA364780, AI015047, AW137324, H42881, AA325059, AI831833, H22172, AA897415, F03562, 845025, F03423, AA382960, T82311, AW401787, AA382959, AW373232, AC018571, AC018571, AC015651, AC015651, AC015651, AC046185, and AC046185.

HWAFS18 245 948434 1 - 946 15 - W25237, and AF156884.

HWLEA48 247 927676 1 - 415 15 - AA130828, AF169034, 298752, 429 and AF 169033.

HWLHS82 248 934505 1 - 415 15 - AW401390, and AC005581.

HWMIB81 249 955336 1 - 147915 - AW380440, AW299858, AW391525, 1493 H78769, H78659, H53674, AA628987, AA447173, AW204470, AA343468, AA480342, AF155118, AC021719, and AC016143.

HuF.$jJ73275 11514831 - 100715 -HHEMAl 276 11514841 - 638 15 -l 652 HODFYl6 291 11052441 - 797 15 -HWHGY45 304 9116211 - 191 15 - AC021102.

HHPDV86 310 522953I - 666 15 -'680AL109627, AL109627, AC025928, and AC025928.

HCHOK82 316 _ 1 - 1077 15 -HFPCH24 317 _ I - 474 15 -HTTKF86 318 _ 1 - 332 15 - 282188, 282188, and 282188.

HCESA79 319 9127091 - 302 15 - AC012171, AC012171, ACOI2171, 316 AC009065, AC009065, AC009065, AC005346, AC005346, and AC005346.

HDTBJ28 320 9127141 - 521 15 - AP001793, AC008052, AC008052, 535 ACOI5676, AC015676, and AP000864.

HEO A56 324 9251321 - 413 15 - AC013449.

HTPC 325 9253491 - 436 15 - 299716, and 299716.

HWAEI37 326 9294811 - 403 15 - AL035461, and AL035461.

HSLEM44 330 5066041 - 337 15 - AC078913, AC022123, and AC010357.

HLWBR95 335 7344741 - 908 15 - AC013252, and ACOI3252.

HMSOZ55 340 9109111 - 979 15 - AC024229, and AC024229.

HMCAV88 347 9248741 - 1031 15 - AC068231, AC068231, AC068231, AL357752, AL357752, AC005476, and AC005476.

uK_A_IP73348 9288091 - 1441 15 -HFVHV40 349 9458491 - 668 15 - AC020911, AC020911, and AC020911.

HEAAE08 35I 9599701 - 1053 15 - AC008687, and AC008687.

HAPRM21 353 9632001 - 857 15 - AL034374, AL034374, and AL034374.

H2CBN90 3_55 9669191 - 809 15 -HTADZ74 358 8114891 - 602 15 - AF077346, AC007278, and AC007278.

HAPNZ77 359 8870721 - 469 15 - AC003046, AC005859, AC076973, AC003046, AC005859, AC023098, and AC023098.

HELDR74 360 9630011 - 1414 15 - AI741422, AW249482, AA573909, AA085764, AW272801, AI052311, AA151131, AI700257, AA490620, AA310938, AI683396, AI284596, AA961817, AA862960, AW073675, 887485, AI828443, AI925221, AI969547, AW001375, N24896, AI521481, AI925228, AI695515, AA609182, AA151130, AI245859, AA490809, AA040451, AW139250, AI970384, AI961068, T67610, AA923298, AA513675, AW027490, T96070, AI624751, T67494, AI936161, AW196036, AA679554, AI917354, N36317, AA302588, AI932690, AW250249, 888163, T72363, AI796143, W32439, AA582049, AI539047, W45013, and AF113795.

HMVDZ78 363 9385741 - 236 15 - AB002313.

HTSFJ40 364 7224061 - 378 15 - W28953, H19139, 854508, HI0122, 392 H08285, AA313257, 859784, F08505, 852605, 243765, F08180, AI401170, F05493, F07194, RI3670, R1364I, 245409, AW407594, F07185, AW407965, AA461135, AA371650, AC006171, AC006171, and AL161645.

HEMBZ62 365 7425511 - 458 15 - 813025.

HHFGZ38 366 7855911 - 1153 15 - AA372117, AA133546, and AI468754.

HSDJH12 368 876344 1 - 610 15 - AA428452, AAI34294, T83462, 624 AI219740, AA010048, AI478566, AI990289, AC021747, AL359882, and AC046143.

HNBUTO1 369 913838 1 - 109015 - AI219740, AI478566, AI632246, 1104 AA279757, AA977612, AA716656, AA687260, AI801069, AA071046, AI985849, AW370598, AA6306I7, AW370599, AW370625, AA134295, AW390691, AI990289, AA134294, AA428452, AI143764, D30955, AW370620, AA352142, AA074442, T83462, AW071043, T79236, and AI744728.

HEOQN14 370 923752 1 - 103115 - AI014538, AW006457, AI479414, 1045 AI805243, AI290929, AI129301, AI872459, AI601146, AI708870, AI973043, AI540074, AI186894, AI682389, AI654747, AA460832, AI392777, AA405714, AA649837, AI356090, AI358510, AW294364, AA954900, AA991687, AI540589, AI953865, AA977875, AW190678, 861326, 854477, AW009738, AA724308, AW297I00, 854409, AA627570, AA504833, AA489470, H08185, 808582, AA778454, AI810108, 241744, 843473, AA765208, AI698394, 239824, H19140, 241120, F03843, AA701889, AA159318, AW408231, AA404221, H84256, AW131981, AI401170, AA405779, AI475002, F01761, AW 189730, H84262, F04422, AA404687, AA502309, AA37I650, H29I88, AA58I ISI, AA477301, AA749407, AA477302, and AI144326.

HTXKL.86 371 928194 1 - 767 15 - AI810108, W28953, AA313257, 781 AI401170, AW408231, AA371650, H19139, 854508, H10122, 859784, H08285, F08505, 243765, AI014538, AA504833, 852605, F08180, AA765208, F05493, AA461135, F07194, 813641, AA70I889, AA159318, 245409, AW407594, H84256, AA404221, 813670, F07185, H84262, AA404687, AW407965, AI144326, AW006457, and AA581151.

HE8TM80 373 955022 1 - 741 15 - 856714, AA125853, AA127005, 755 H06566, T70821, AA307834, H53723, and AFI910I8.

HWLEY40 374 957875 1 - 144315 - W28953, AI810108, AA159318, 1457 AA461135, H10122, AA313257, AA701889, AI654981, AI401170, H19139, H08285, AW408231, AA371650, 854508, 859784, AW407594, F07194, AA504833, F08180, F08505, 243765, 852605, F07185, H84256, AW407965, F05493, H84262, AA404221, 813670, AA765208, 245409, AA404687, 813641, AI014538, AI144326, AC006171, AC006171, and AL161645.

HOUBZ94 376 527876 1 - 139 15 - AC005954, AC005954, and AC068475.

HCE3W04 379 615501 1 - 859 15 - AC025165, AC025165, AC022506, AC022506, and AC022366.

~ 363 HPJAP28 382 6863491 - 432 15 - AC004794, AC004794, and AC004794.

HIBEC79 383 7030001 - 325 15 - AC011458, AC011458, and AC011458.

HNFHS82 387 7799461 - 401 15 - AC010835.

HFPBB28 389 8445261 - 321 15 - AC016135, AC002518, AC073717, 335 and AC018512.

HD GZ78 399 9097351 - 428 15 - AC026282.

HSID 401 9098541 - 783 15 - AC003070.

HFTBL33 407 9100551 - 1475 15 - AC025165, AC025165, and AC022366.

HUFCI64 411 9I 1 - 759 15 - AC00415I, and AC004I5I.

HWAFT84 412 9115591 - 1342 15 - AC004151, and AC004151.

HTPFA03 4'15 9227651 - 315 15 -HWADR60 416 9264871 - 1275 15 - AC023176, and AC023176.

HPCIG66 419 9308861 - 945 15 - AC024888, AC024888, and AC024888.

HCRPU72 420 9311401 - 931 15 - AC023151.

HE9RT95 421 9345561 - 804 15 - AC022420, AC022420, AC022420, 818 and AC008439.

HWADD57 426 9430391 - 996 15 - AC011492, and AC011492.

HBXDJ07 429 9468301 - 1470 15 - H11405, 855569, N27906, H20863, 1484 N25140, and U27708.

HFKHR40 431 9524701 - 2240 15 - AC061707, AC061707, AC061707, 2254 AC018805, and AC018805.

HWLHF10 435 963422I - 1387 15 - ACOI0545, AC010545, and AC010545.

HNNAS46 438 9694701 - 1493 15 -'1507 Code Description Tissue Organ ell Di easeVector Lin AR022a Heart a Heart AR023a Liver a Liver AR024a mammar land a mammary land AR025a Prostate a Prostate AR026a small intestinea small intestine AR027a Stomach a Stomach AR028Blood B cells Blood B cells AR029Blood B cells Blood B cells activated activated AR030Blood B cells Blood B cells resting restin AR031Blood T cells Blood T cells activated activated AR032Blood T cells Blood T cells restin restin AR033brain brain AR034breast breast AR035breast cancer breast cancer AR036CeII Line CAOV3 Cell Line AR037cell line PA-1 cell line AR038cell line transformedcell line transformed AR039colon colon AR040colon (9808co65R)colon (9808co65R) AR041colon(9809co15) colon(9809co15) AR042colon cancer colon cancer AR043colon cancer colon cancer (9808co64R) (9808co64R) AR044colon cancer colon cancer 9809co14 9809co14 AR045corn clone 5 corn clone AR046corn clone 6 corn clone AR047corn clone2 corn clone2 AR048corn clone3 corn clone3 AR049Corn Clone4 Corn Clone4 AR050Donor II B CellsDonor II
24hrs B Cells 24hrs AR051Donor a B Cells Donor II
72hrs B Cells 72hrs AR052Donor II B-CellsDonor II
24 hrs. B-Cells hrs.

AR053Donor II B-CellsDonor II
72hrs B-Cells 72hrs AR054Donor II RestingDonor II
B Cells Resting B
Cells AR055Heart Heart AR056Human Lung (clonetech)Human Lung (clonetech) AR057Human Mammary Human Mammary (clontech) (clontech) AR058Human Thymus Human Thymus (clonetech) (clonetech) AR059Jurkat (unstimulated)Jurkat (unstimulated) AR060Kidney Kidney AR061Liver Liver AR062Liver (Clontech)Liver (Clontech) AR063Lymphocytes chronicLymphocytes lymphocytic leukaemiachronic lymphocytic leukaemia AR064Lymphocytes diffuseLymphocytes large B cell lymphoma diffuse large B cell lymphoma AR065Lymphocytes follicularLymphocytes I m homa follicular 1 m homa AR066normal breast normal breast AR067Normal Ovarian Normal Ovarian (4004901) (4004901) AR068Normal Ovary Normal Ovary AR069Normal Ovary Normal Ovary AR070Normal Ovary Normal Ovary ' AR071Ovarian Cancer Ovarian Cancer AR072Ovarian Cancer Ovarian Cancer (97026001) (97026001) AR073Ovarian Cancer Ovarian Cancer (97076029) (97076029) AR074Ovarian Cancer Ovarian Cancer (98046011) (98046011) AR075Ovarian Cancer Ovarian Cancer (98066019) (98066019) AR076Ovarian Cancer Ovarian Cancer (98076017) (98076017) AR077Ovarian Cancer Ovarian Cancer (98096001) (98096001) AR078ovarian cancer ovarian cancer AR079Ovarian Cancer Ovarian Cancer AR080Ovarian Cancer Ovarian Cancer AR081Ovarian Cancer Ovarian Cancer AR082ovarian cancer ovarian cancer AR083Ovarian Cancer Ovarian Cancer AR084Ovarian Cancer Ovarian Cancer AR085Ovarian Cancer Ovarian Cancer AR086ovarian cancer ovarian 98096001 cancer AR087Ovarian Cancer Ovarian 9905C032RC Cancer AR088Ovarian cancer Ovarian 9907 C00 cancer 3rd 9907 C00 3rd AR089Prostate Prostate AR090Prostate (clonetech)Prostate . (clonetech) AR091rostate cancer rostate cancer AR092prostate cancer prostate #15176 cancer #15176 AR093prostate cancer prostate #15509 cancer #15509 AR094prostate cancer prostate #15673 cancer #15673 AR095Small Intestine Small Intestine (Clontech) (Clontech) AR096S Teen S leen AR097Thymus T cells Thymus T
activated cells activated AR098Thymus T cells Thymus T
resting cells restin AR099Tonsil Tonsil AR100Tonsil geminal Tonsil geminal center center centroblast centroblast AR101Tonsil germinal Tonsil germinal center B center B
cell cell AR102Tonsil lym h Tonsil lym node h node AR103Tonsil memory Tonsil memory B cell B
cell AR104Whole Brain Whole Brain AR Xeno raft ES-2 Xeno raft AR106Xeno raft SW626 Xeno raft H0002Human Adult HeartHuman AdultHeart Uni-ZAP
Heart XR

H0004Human Adult SpleenHuman AdultSpleen Uni-ZAP
S leen XR

H0008Whole 6 Week Uni-ZAP
Old XR
Emb o H0009Human Fetal Brain Uni-ZAP
XR

H0011Human Fetal KidneHuman FetalKidne Uni-ZAP
Kidne XR

H0012Human Fetal KidneHuman FetalKidne Uni-ZAP
Kidne XR

H0013Human 8 Week Human 8 Embryo Uni-ZAP
Whole Week Old XR
Emb o Emb o H0014Human Gall BladderHuman Gall Gall Bladder Uni-ZAP
Bladder XR

H0015Human Gall Bladder,Human Gall Gall Bladder Uni-ZAP
fraction II Bladder XR

H0022Jurkat Cells Jurkat T-Cell Lambda Line ZAP II

H0023Human Fetal Lun Uni-ZAP
XR

H0024Human Fetal Lun Human FetalLun Uni-ZAP
III Luno XR

H0025Human Adult LymphHuman AdultLymph Lambda Node L m h Node Node ZAP II

H0026Namalwa Cells Namalwa Lambda B-CeII ZAP II

Line, EBV
immortalized H0027Human Ovarian diseaseUni-ZAP
Cancer XR

H0028Human Old Ovar Human Old Ovary Bluescri Ova t H0029Human Pancreas Human PancreasPancreas Uni-ZAP
XR

H0030Human Placenta Uni-ZAP
XR

H0031Human Placenta Human PlacentaPlacenta Uni-ZAP
XR

H0032Human Prostate Human ProstateProstate Uni-ZAP
XR

H0033Human Pituita Human Pituita Uni-ZAP
XR

H0036Human Adult Human Adult Small Uni-ZAP
Small Small Int. XR
Intestine Intestine H0037Human Adult Human Adult Small pBluescript Small Small Int.
Intestine Intestine H0038Human Testes Human TestesTestis Uni-ZAP
XR

H0039Human Pancreas Human PancreasPancreas diseaseUni-ZAP
Tumor Tumor XR

H0040Human Testes Human TestesTestis diseaseUni-ZAP
Tumar Tumor XR

H0041Human Fetal Human Fetal Bone Uni-ZAP
Bone Bone XR

H0042Human Adult Human Adult Lung Uni-ZAP
Pulmonary Pulmona XR

H0046Human EndometrialHuman EndometrialUterus diseaseUni-ZAP
Tumor Tumor XR

H0050Human Fetal Human Fetal Heart Uni-ZAP
Heart Heart XR

H0051Human HippocampusHuman Brain Uni-ZAP
Hippocampus XR

H0052Human CerebellumHuman CerebellumBrain Uni-ZAP
XR

H0056Human UmbilicalHuman UmbilicalUmbilical Uni-ZAP
Vein, Vein Endothelialvein XR
Endo. remake Cells H0057Human Fetal Uni-ZAP
S leen XR

H0059Human Uterine Human UterineUterus diseaseLambda ZAP
Cancer Cancer II

H0063Human Th mus Human ThymusTh mus Uni-ZAP
XR

H0064Human Right Human Brain,Brain Uni-ZAP
Hemisphere right XR
of Brain hemis here H0068Human Skin TumorHuman Skin Skin diseaseUni-ZAP
Tumor XR

H0069Human ActivatedActivated Blood Cell Uni-ZAP
T-Cells T-Cells Line XR

H0071Human Infant Human InfantAdrenal Uni-ZAP
Adrenal Adrenal Glandland XR
Gland H0075Human ActivatedActivated Blood Cell Uni-ZAP
T-Cells T-Cells Line XR
(II) H0079Human Whole Human Whole Embryo Uni-ZAP
7 Week 7 XR
Old Emb o (II) Week Old Embr o H0081Human Fetal Human Fetal Skin Uni-ZAP
Epithelium Skin XR
(Skin) H0082Human Fetal Human Fetal Sk Muscle Uni-ZAP
Muscle Muscle XR

H0083HUMAN JURKAT Jurkat Cells Uni-ZAP
MEMBRANEBOUND XR
POLYSOMES

H0085Human Colon Human Colon Lambda ZAP
II

H0086Human a ithelioidE ithelioid Sk Muscle diseaseUni-ZAP
XR

sarcoma Sarcoma, muscle H0087Human Th mus Human Thymus Bluescri t H0090Human T-Cell T-Cell Lym T-Cell diseaseUni-ZAP
L m homa homa XR

H0092Human Pancreas Human PancreasPancreas diseaseUni-ZAP
Tumor XR

Tumor H0098Human Adult Liver,Human Adult Liver Uni-ZAP
Liver XR

subtracted HO100Human Whole Six Human Whole Embryo Uni-ZAP
Week Six XR

Old Emb o Week Old Emb o HO101Human 7 Weeks Human Whole Embryo Lambda ZAP
Old 7 II

Embryo, subtractedWeek Old Emb o H0102Human Whole 6 Human Whole Embryo pBluescript Week Six Old Emb o (II), Week Old subt Emb o HO105Human Fetal Heart,Human Fetal Heart pBluescript Heart subtracted H0107Human Infant Human InfantAdrenal pBluescript Adrenal Gland, subtractedAdrenal Glandland H0108Human Adult LymphHuman Adult Lymph Uni-ZAP
Node XR

Node, subtractedLym h Node HO111Human Placenta, Human PlacentaPlacenta pBluescript subtracted H0112Human ParathyroidHuman ParathyroidParathyroid pBluescript Tumor, subtractedTumor H0118Human Adult KidneyHuman Adult Kidney Uni-ZAP
XR

Kidne H0122Human Adult SkeletalHuman SkeletalSk Muscle Uni-ZAP
XR

Muscle Muscle H0123Human Fetal DuraHuman Fetal Brain Uni-ZAP
Mater Dura XR

Mater H0124Human Human Sk Muscle diseaseUni-ZAP
XR

RhabdomyosarcomaRhabdomyosarcoma H0125Cem cells cyclohexamideCyclohexamideBlood Cell Uni-ZAP
Line XR

treated Treated Cem, Jurkat, Ra'i, and Su t H0130LNCAP untreated LNCAP Cell ProstateCell Uni-ZAP
Line Line XR

H0131LNCAP + o.3nM LNCAP Cell ProstateCell Uni-ZAP
81881 Line Line XR

H0132LNCAP + 30nM LNCAP Cell ProstateCell Uni-ZAP
81881 Line Line XR

H0134Raji Cells, cyclohexamideCyclohexamideBlood Cell Uni-ZAP
Line XR

treated Treated Cem, Jurkat, Raji, and Supt H0135Human Synovial Human SynovialSynovium Uni-ZAP
Sarcoma XR

Sarcoma H0136Supt Celts, cyclohexamideCyclohexamideBlood Cell Uni-ZAP
Line XR

treated Treated Cem, Jurkat, Raji, and Su t H0140Activated T-Cells,Activated Blood Cell Uni-ZAP
8 hrs. T-Cells Line XR

H0144Nine Week Old 9 Wk Old Embryo Uni-ZAP
Early Early XR

Stage Human Stage Human H01497 Week Old EarlyHuman Whole Embryo Uni-ZAP
Stage 7 XR

Human, subtractedWeek Old Embr o HO150Human E idid E idid mis Testis Uni-ZAP
mus XR

H0152Early Stage HumanHuman Fetal Liver Uni-ZAP
Liver, Liver XR

fract(II) H0154Human FibrosarcomaHuman Skin Skin diseaseUni-ZAP
XR

Fibrosarcoma H0156Human Adrenal Human AdrenalAdrenal diseaseUni-ZAP
Gland XR

Tumor Gland Tumor Gland H0159Activated T-Cells,Activated Blood Cell Uni-ZAP
8 hrs., T-Cells Line XR

1i ation 2 H0161Activated T-Cells,Activated Blood Cell Uni-ZAP
24 hrs., T-Cells Line XR

1i ation 2 H0163Human Synovium Human S noviumS novium Uni-ZAP
XR

H0165Human Prostate Human ProstateProstate diseaseUni-ZAP
Cancer, XR

Sta a B2 Cancer, sta a B2 H0166Human Prostate Human ProstateProstate diseaseUni-ZAP
Cancer, XR

Stage B2 fractionCancer, stage H0169Human Prostate Human ProstateProstate diseaseUni-ZAP
Cancer, XR

Sta a C fractionCancer, sta a C

H017012 Week Old EarlyTwelve Week Embryo Uni-ZAP
Stage Old XR

Human Earl Sta a Human H017112 Week Old EarlyTwelve Week Embryo Uni-ZAP
Stage Old XR

Human, II Earl Sta a Human H0172Human Fetal Brain,Human Fetal Brain Lambda ZAP
Brain II

random primed H0175H. Adult Spleen, pSportl ziplox H0177CAMAIEe CeII CAMAlEe CellBreast Cell Uni-ZAP
Line Line XR

Line H0178Human Fetal BrainHuman Fetal Brain Uni-ZAP
Brain XR

H0179Human Neutro Human NeutroBlood Cell Uni-ZAP
hil hil Line XR

H0180Human Primary Human PrimaryBreast diseaseUni-ZAP
Breast XR

Cancer Breast Cancer H0181Human Primary Human PrimaryBreast diseaseUni-ZAP
Breast XR

Cancer Breast Cancer H0182Human Primary Human PrimaryBreast diseaseUni-ZAP
Breast XR

Cancer Breast Cancer H0187Restin T-Cell T-Cells Blood Cell Lambda ZAP
Line II

H0188Human Normal Human NormalBreast Uni-ZAP
Breast XR

Breast H0189Human Resting Human Blood Cell Uni-ZAP
Line XR

Macrophage Macrophage/Monoc ytes H0191Human Activated Human Blood Cell Uni-ZAP
Line XR

Macrophage (LPS),Macrophage/Monoc thiour tes H0194Human Cerebellum,Human CerebellumBrain pBluescript subtracted H0196Human Cardiomyopathy,Human Heart Uni-ZAP
XR

subtracted Cardiom o ath H0197Human Fetal Liver,Human Fetal Liver Uni-ZAP
Liver XR

subtracted H0199Human Fetal Liver,Human Fetal Liver Uni-ZAP
Liver XR

subtracted, ne clone H0201Human Hippocampus,Human Brain pBluescript subtracted Hi ocam us H0208Early Stage HumanHuman Fetal Lung pBluescript Lung, Lung subtracted H0212Human Prostate,Human ProstateProstate pBluescript subtracted H0213Human Pituitary,Human Pituitary Uni-ZAP
XR

subtracted H0216Supt cells, CyclohexamideBlood Cell pBluescript cyclohexamide Line treated, subtractedTreated Cem, Jurkat, Raji, and Su t H0217Supt cells, CyclohexamideBlood Cell pBluescript cyclohexamide Line treated, differentiallyTreated Cem, Jurkat, ex ressed Ra'i, and Su t H0222Activated T-Cells,Activated Blood Cell Uni-ZAP
8 hrs, T-Cells Line XR

subtracted H023IHuman Colon, Human Colon BIuescri subtraction t H0233Human Fetal Human Fetal Heart pBluescript Heart, Heart Differential (Adult-s ecific) H0234human colon Human Colon Liver pBluescript cancer, metastatic to Cancer, metasticized liver, differentially to liver ex ressed H0235Human colon Human Colon Liver pBluescript cancer, metaticized Cancer, metasticized to liver, subtraction to liver H0239Human Kidney Human KidneyKidney diseaseUni-ZAP
Tumor XR

Tumor H0241C7MCF7 cell C7MCF7 Cell Breast Cell Uni-ZAP
line, Line, Line XR

estrogen treated,estrogen treated subtraction H0244Human 8 Week Human 8 WeekEmbryo Uni-ZAP
Whole Old XR

Embr o, subtractedEmb o H0246Human Fetal Human Fetal Liver Uni-ZAP
Liver- Liver XR

Enzyme subtraction H0247Human Membrane Human MembraneBlood Cell Uni-ZAP
Bound Line XR

Polysomes- EnzymeBound Polysomes Subtraction H0249HE7, subtractedHuman Whole Embryo Uni-ZAP
by 7 XR

hybridization Week Old with E7 Embryo cDNA

H0250Human ActivatedHuman Monocytes Uni-ZAP
XR

Monocytes H0251Human ChondrosarcomaHuman Cartilage diseaseUni-ZAP
XR

Chondrosarcoma H0252Human OsteosarcomaHuman Bone diseaseUni-ZAP
XR

Osteosarcoma H0253Human adult Human Adult Testis Uni-ZAP
testis, large Testis XR

inserts H0254Breast Lymph Breast LymphLymph Uni-ZAP
node cDNA Node Node XR

Libra H0255breast lymph Breast LymphLymph Lambda node CDNA Node Node ZAP II

Libra H0257HL-60, PMA 4H HL-60 Cells,Blood Cell Uni-ZAP
PMA Line XR

stimulated H0261H. cerebellum, Human CerebellumBrain Uni-ZAP
Enzyme XR

subtracted H0263human colon Human Colon Colon diseaseLambda ZAP
cancer II

Cancer H0264human tonsils Human Tonsil Tonsil Uni-ZAP
XR

H0265Activated T-CeIIT-Cells Blood Celi Uni-ZAP
Line XR

( l2hs)fThiouridine labelledEco H0266Human MicrovascularHMEC Vein Cell Lambda ZAP
Line II

Endothelial Cells, fract.
A

H0267Human MicrovascularHMEC Vein Cell Lambda ZAP
Line II

Endothelial Cells, fract.
B

H0268Human UmbilicalHUVE Cells UmbilicalCell Lambda ZAP
Vein Line II

Endothelial vein Cells, fract.
A

H0269Human UmbilicalHUVE Cells UmbilicalCell Lambda ZAP
Vein Line II

Endothelial vein Cells, fract.
B

H0271Human Neutrophil,Human NeutrophilBlood Cell Uni-ZAP
- Line XR

Activated Activated H0272HUMAN TONSILS, Human Tonsil Tonsil Uni-ZAP
XR

H0280K562 + PMA (36 K562 Cell cell Cell ZAP Ex ress hrs) line line Line H0282HBGB"s differentialHuman PrimaryBreast Uni-ZAP
XR

consolidation Breast Cancer H0284Human OB MG63 Human Bone Cell Uni-ZAP
control Line XR

fraction I Osteoblastoma MG63 cell line H0286Human OB MG63 Human Bone Cell Uni-ZAP
treated Line XR

(10 nM E2) fractionOsteoblastoma I

MG63 cell line H0288Human OB HOS Human Bone Cell Uni-ZAP
control Line XR

fraction I Osteoblastoma HOS

cell line H0290Human O$ HOS Human Bone Cell Uni-ZAP
treated Line XR

( 1 nM E2) fractionOsteoblastoma I HOS

cell line H0292Human OB HOS Human Bone Cell Uni-ZAP
treated Line XR

(10 nM E2) fractionOsteoblastoma I HOS

cell line H0294Amniotic Cells Amniotic CellsPlacentaCell Uni-ZAP
- TNF - Line XR

induced TNF induced H0295Amniotic Cells Amniotic CellsPlacentaCell Uni-ZAP
- Primary - Line XR

Culture Primary Culture H0298HCBB"s differentialCAMAlEe Cell Breast Cell Uni-ZAP
Line XR

consolidation Line H0299HCBA"s differentialCAMAlEe Cell Breast Cell Uni-ZAP
Line XR

consolidation Line H0300CD34 positive CD34 PositiveCord ZAP Express cells (Cord Cells Blood Blood) H0305CD34 positive CD34 PosifiveCord ZAP Express cells (Cord Cells Blood Blood) H0306CD34 depleted CD34 DepletedCord ZAP Express Buffy Coat Blood (Cord Blood) Buffy Coat (Cord Blood) H0309Human Chronic Synovium, Synovium diseaseUni-ZAP
Synovitis Chronic XR

Synovitisl Osteoarthritis H0310human caudate Brain Brain Uni-ZAP
nucleus XR

H0316HUMAN STOMACH Human StomachStomach Uni-ZAP
XR

H0318HUMAN B CELL Human B CellLymph diseaseUni-ZAP
LYMPHOMA Lymphoma Node XR

H0320Human frontal Human FrontalBrain Uni-ZAP
cortex Cortex XR

H0327human corpus Human CorpusBrain Uni-ZAP
colosum Callosum XR

H0328human ovarian Ovarian CancerOvar diseaseUni-ZAP
cancer XR

H0329DermatofibrosarcomaDermatofibrosarcomSkin diseaseUni-ZAP
Protuberance a Protuberans XR

H0331Hepatocellular HepatocellularLiver diseaseLambda ZAP
Tumor Tumor II

H0333HemangiopericytomaHemangiopericytomBlood diseaseLambda ZAP
a vessel II

H0334Kidney cancer Kidney CancerKidne diseaseUni-ZAP
XR

H0339Duodenum Duodenum Uni-ZAP
XR

H0340Corpus CallosumCorpus Collosum- Uni-ZAP

H0341Bone Marrow Bone Marrow Bone MarrowCell Uni-ZAP
Cell Line Cell Line XR
(RS4;11) Line RS4;11 H0342Lin ual G rus Lin ual G Brain Uni-Za XR
rus H0343stomach cancer Stomach Cancer diseaseUni-ZAP
(human) - XR
5383A (human) H0345SKIN Skin - 4000868HSkin Uni-ZAP
XR

H0349human adult Human Adult Liver pCMVSport liver cDNA Liver 1 libr H0351Glioblastoma GlioblastomaBrain diseaseUni-ZAP
XR

H03524vilm"s tumor Wilm"s Tumor diseaseUni-ZAP
XR

H0355Human Liver Human Liver, pCMVSport normal Adult 1 H0356Human Kidne Human Kidne Kidney CMVS ort H0359KMH2 cell line KMH2 ZAP Ex ress H0361Human rejected Human Rejected diseasepBluescript kidney Kidne H0364Human Osteoclastoma,Human diseasepBluescript excised Osteoclastoma H0365Osteoclastoma-normalizedHuman diseaseUni-ZAP
B Osteoclastoma XR

H0366IA~28 cell lineL428 ZAP Ex ress H0369H. Atrophic Atrophic Uni-ZAP
Endometrium Endometrium XR
and myometrium H0370H. Lymph node Lymph node diseaseUni-ZAP
breast with XR
Cancer Met. Breast Cancer H0372Human Testes Human TestesTestis CMV S ort H0373Human Heart Human Adult Heart CMV S ort Heart 1 H0374Human Brain Human Brain CMVS ort H0375Human Lun Human Lun CMVS ort H0376Human Spleen Human Adult Spleen pCMVSport S leen 1 DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

~~ TTENANT LES PAGES 1 A 465 NOTE : Pour les tomes additionels, veuillez contacter 1e Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME

NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME
NOTE POUR LE TOME / VOLUME NOTE:

Claims (24)

What Is Claimed Is:
1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
(a) a polynucleotide fragment of SEQ ID NO:X or a polynucleotide fragment of the cDNA sequence contained in Clone ID NO:Z, which is hybridizable to SEQ ID
NO:X;
(b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:Y or a polypeptide fragment encoded by the cDNA sequence contained in cDNA Clone ID
NO:Z, which is hybridizable to SEQ ID NO:X;
(c) a polynucleotide encoding a polypeptide fragment of a polypeptide encoded by SEQ ID NO:X or a polypeptide fragment encoded by the cDNA sequence contained in cDNA Clone ID NO:Z, which is hybridizable to SEQ ID NO:X;
(d) a polynucleotide encoding a polypeptide domain of SEQ ID NO:Y or a polypeptide domain encoded by the cDNA sequence contained in cDNA Clone ID
NO:Z, which is hybridizable to SEQ ID NO:X;
(e) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitope encoded by the cDNA sequence contained in cDNA Clone ID
NO:Z, which is hybridizable to SEQ ID NO:X;
(f) a polynucleotide encoding a polypeptide of SEQ ID NO:Y or the cDNA
sequence contained in cDNA Clone ID NO:Z, which is hybridizable to SEQ ID NO:X, having biological activity;
(g) a polynucleotide which is a variant of SEQ ID NO:X;
(h) a polynucleotide which is an allelic variant of SEQ ID NO:X;
(i) a polynucleotide which encodes a species homologue of the SEQ ID NO:Y;
(j) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A
residues or of only T residues.
2. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a protein.
3. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding the sequence identified as SEQ ID NO:Y
or the polypeptide encoded by the cDNA sequence contained in cDNA Clone ID
NO:Z, which is hybridizable to SEQ ID NO:X.
4. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises the entire nucleotide sequence of SEQ ID NO:X or the cDNA
sequence contained in cDNA Clone ID NO:Z, which is hybridizable to SEQ ID NO:X.
5. The isolated nucleic acid molecule of claim 2, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.
6. The isolated nucleic acid molecule of claim 3, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.
7. A recombinant vector comprising the isolated nucleic acid molecule of claim 1.
8. A method of making a recombinant host cell comprising the isolated nucleic acid molecule of claim 1.
9. A recombinant host cell produced by the method of claim 8.
10. The recombinant host cell of claim 9 comprising vector sequences.
11. An isolated polypeptide comprising an amino acid sequence at least 90%
identical to a sequence selected from the group consisting of:
(a) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence contained in cDNA Clone ID NO:Z;
(b) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence contained in cDNA Clone ID NO:Z, having biological activity;

(c) a polypeptide domain of SEQ ID NO:Y or the encoded sequence contained in cDNA Clone ID NO:Z;

(d) a polypeptide epitope of SEQ ID NO:Y or the encoded sequence contained in cDNA Clone ID NO:Z;

(e) a full length protein of SEQ ID NO:Y or the encoded sequence contained in cDNA
Clone ID NO:Z;
(f) a variant of SEQ ID NO:Y;
(g) an allelic variant of SEQ ID NO:Y; or (h) a species homologue of the SEQ ID NO:Y.
12. The isolated polypeptide of claim 11, wherein the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.
13. An isolated antibody that binds specifically to the isolated polypeptide of claim 11.
14. A recombinant host cell that expresses the isolated polypeptide of claim 11.
15. A method of making an isolated polypeptide comprising:
(a) culturing the recombinant host cell of claim 14 under conditions such that said polypeptide is expressed; and (b) recovering said polypeptide.
16. The polypeptide produced by claim 15.
17. A method for preventing, treating, or ameliorating a medical condition, comprising administering to a mammalian subject a therapeutically effective amount of the polynucleotide of claim 1.
18. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:
(a) determining the presence or absence of a mutation in the polynucleotide of claim 1; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.
19. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:
(a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.
20. A method for identifying a binding partner to the polypeptide of claim 11 comprising:
(a) contacting the polypeptide of claim 11 with a binding partner; and (b) determining whether the binding partner effects an activity of the polypeptide.
21. The gene corresponding to the cDNA sequence of SEQ ID NO:Y.
22. A method of identifying an activity in a biological assay, wherein the method comprises:
(a) expressing SEQ ID NO:X in a cell;
(b) isolating the supernatant;
(c) detecting an activity in a biological assay; and identifying the protein in the supernatant having the activity.
23. The product produced by the method of claim 20.
24. A method for preventing, treating, or ameliorating a medical condition, comprising administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 11.
CA002395816A 2000-01-31 2001-01-17 Nucleic acids, proteins and antibodies Withdrawn CA2395816A1 (en)

Applications Claiming Priority (235)

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Publications (1)

Publication Number Publication Date
CA2395816A1 true CA2395816A1 (en) 2001-08-02

Family

ID=27587117

Family Applications (37)

Application Number Title Priority Date Filing Date
CA002395885A Withdrawn CA2395885A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395671A Withdrawn CA2395671A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002393618A Abandoned CA2393618A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392438A Abandoned CA2392438A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395849A Pending CA2395849A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395699A Pending CA2395699A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395858A Withdrawn CA2395858A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002393652A Withdrawn CA2393652A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392751A Abandoned CA2392751A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395729A Pending CA2395729A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395403A Withdrawn CA2395403A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395666A Withdrawn CA2395666A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002394841A Withdrawn CA2394841A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395827A Withdrawn CA2395827A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002393002A Withdrawn CA2393002A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002397839A Withdrawn CA2397839A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392398A Abandoned CA2392398A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395693A Pending CA2395693A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392450A Abandoned CA2392450A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395738A Withdrawn CA2395738A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395295A Withdrawn CA2395295A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins and antibodies
CA002397407A Withdrawn CA2397407A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002398411A Withdrawn CA2398411A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392428A Abandoned CA2392428A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392422A Abandoned CA2392422A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392757A Abandoned CA2392757A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002394039A Abandoned CA2394039A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395872A Withdrawn CA2395872A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395816A Withdrawn CA2395816A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins and antibodies
CA002395178A Withdrawn CA2395178A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395734A Withdrawn CA2395734A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002398877A Withdrawn CA2398877A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395787A Withdrawn CA2395787A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002393912A Withdrawn CA2393912A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395654A Withdrawn CA2395654A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395398A Withdrawn CA2395398A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395724A Pending CA2395724A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies

Family Applications Before (28)

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CA002395885A Withdrawn CA2395885A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395671A Withdrawn CA2395671A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002393618A Abandoned CA2393618A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392438A Abandoned CA2392438A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395849A Pending CA2395849A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395699A Pending CA2395699A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395858A Withdrawn CA2395858A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002393652A Withdrawn CA2393652A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002392751A Abandoned CA2392751A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395729A Pending CA2395729A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395403A Withdrawn CA2395403A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395666A Withdrawn CA2395666A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002394841A Withdrawn CA2394841A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
CA002395827A Withdrawn CA2395827A1 (en) 2000-01-31 2001-01-17 Nucleic acids, proteins, and antibodies
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