Human secreted proteins

[0001] The present invention relates to human secreted proteins/polypeptides, and isolated nucleic acid molecules encoding said proteins/polypeptides, useful for detecting, preventing, diagnosing, prognosticating, treating, and/or ameliorating gastrointestinal diseases and disorders. Antibodies that bind these polypeptides are also encompassed by the present invention. Also encompassed by the invention are vectors, host cells, and recombinant and synthetic methods for producing said polynucleotides, polypeptides, and/or antibodies. The invention further encompasses screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further encompasses methods and compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.

[0002] The human digestive system is a collection of specialized organs and body tissues that prepare food for use by hundreds of millions of body cells. Food when eaten cannot reach ceUs because it cannot pass through the intestinal walls to the bloodstream and, if it could would not be in a useful chemical state. The gastrointestinal system modifies food physically and chemically and disposes of unusable waste. Physical and chemical modification (digestion) depends on exocrine and endocrine secretions and controlled movement of food through the digestive tract.

[0003] The three fundamental processes of the digestive. system are: secretion (e.g., delivery of enzymes, mucus, ions and the like into the lumen, and hormones into blood), absorption (e.g., transport of water, ions and nutrients from the lumen, across the epithelium and into blood), and motility (e.g., contractions of smooth muscle in the wall of the tube that crush, mix and propel its contents). Control of digestive function is achieved through a combination of electrical and hormonal messages which originate either within the digestive system's own nervous and endocrine systems, as well as from the central nervous system and from endocrine organs such as the adrenal gland.

[0004] The digestive system is composed of the digestive or alimentary tube and accessory digestive organs, which include the Mouth (e.g., tongue, taste buds, soft palate pharynx, salivary glands, teeth), Esophagus, Stomach, Liver, Gallbladder, Pancreas, Small Intestine (e.g., duodenum, jejunum, and ileum), and Large Intestine (e.g., caecum).

[0005] Common digestive system disorders including infections, inflammations, ulcers and cancers of the digestive or alimentary tube and above listed accessory digestive organs are described in more detail below.

[0006] Disorders of the Mouth

[0007] The mouth comprises an area from the lips to the front of the tonsils (fauces) at the start of the throat. The mouth contains the gums, teeth, and the tongue, together with salivary glands which secrete fluids that lubricate and begin food digestion as it is chewed. The roof of the mouth consists of the hard palate at the front and the soft palate at the back. The floor of the mouth comprises the tongue (controlled by a number of muscles attached to bones in the neck). At the front and sides of the tongue there are a number of taste buds. These respond to different tastes at different places (e.g., sweet, salty, sour, and bitter). At the back of the tongue there are some swellings which consist of lymphoid tissue. Underneath the tongue there is a midline attachment (frenulum) and the opening of several of the salivary ducts. There are other salivary glands (the parotid glands) lying over the angle of the jaw with a duct opening to the inside of the cheek at about the level of the second molar tooth.

[0008] Diseases and disorders of the mouth are vary greatly in manifested symptoms, frequencies, severities, and causes. Accordingly, diseases and disorders of the mouth may be caused or initiated by viruses, bacteria, genetics (e.g. autoimmune disorders), physical or chemical trauma, etc. For example, diseases and disorders of the mouth include canker sores (aphthous ulcers), herpetic stomatitis leukoplakia, gingivostomatitis, oral cancer, oral lichen lanus, oral thrush, histoplasmosis, salivary gland infections, glossitis, Hand, Foot and Mouth disease, salivary duct stones, mumps, etc.

[0009] Disorders of the Esophagus

[0010] Disorders of the Esophagus include dysphagia (e.g., difficulty in swallowing) and odynophagia (e.g., difficulty in swallowing accompanied by pain). Inflammatory disorders of the esophagus result from a variety of causes; for example, ingestion of noxious materials (e.g., corrosive esophagitis), lodgment of foreign bodies, or a complex of events associated with reflux of gastric contents from the stomach into the lower esophagus (e.g., peptic esophagitis).

[0011] Disorders of the motility of the esophagus tend to be either precipitated or aggravated at times of nervous stress. A disorder commonly due to obesity is gastric reflux. Persisting reflux of gastric contents with acid and digesting enzymes leads to chemical inflammation of the lining of the esophagus and ultimately to (peptic) ulceration. If inadequately treated, the process leads to submucosal fibrosis and stricturing, and, besides the symptoms of heartburn and regurgitation, the patient experiences pain on eating and swallowing.

[0012] Further disorders of the esophagus include the formation of diverticula. A serious injury to the esophagus is spontaneous rupture. It can occur in patients who have been vomiting or retching and in debilitated elderly persons with chronic lung disease. A rupture of this type confined to the mucosa only at the junction of the linings of the esophagus and stomach is called a Mallory-Weiss lesion.

[0013] Benign tumors of the esophagus originate in the submucosal tissues and principally are leiomyomas (tumors composed of smooth muscle tissue) or lipomas (tumors composed of adipose, or fat, tissues). Malignant tumors are either epidermal cancers, made up of unorganized aggregates of cells, or adenocarcinomas, in which there are gland-like formations. Cancers arising from squamous tissues are found at all levels of the organ, whereas adenocarcinomas are more common at the lower end where a number of glands of gastric origin are normally present. The prognosis is poor because diagnosis is difficult and the tumor has usually been growing for one or two years before symptoms are apparent.

[0014] Disorders of the Stomach

[0015] Any disorder that affects the power of coordination of the stomach muscles is capable of producing symptoms ranging from those that are mildly unpleasant (e.g., anorexia and nausea) to others that are life-threatening. The intrinsic muscles of the stomach are innervated by branches of the vagus nerves, which travel along the esophagus from their point of emergence in the brain stem. Severing these nerves or altering their function by the use of anticholinergic medication may produce temporary or more prolonged change in the ability of the stomach to empty itself. Gastric retention may result from the degeneration of the nerves to the stomach that can result from diabetes merintus. Obstruction due to scarring in the area of the gastric outlet, or to tumors encroaching on the lumen, causes the stomach to fill up with its own secretions as well as with partially digested food. In these circumstances, vomiting leads to dehydration and to electrolyte losses, which threaten life if not corrected.

[0016] Disorders of the stomach include ulcerative diseases, which involve mucosal breakdown either confined to the superficial layers of the mucosa (e.g., an erosion) or extending through the intrinsic layer of muscle of the mucosa into the tissues below (e.g., an ulcer). The circumstances that contribute to mucosal injury and ulcer formation include physical and chemical trauma that result from hot fluids and food, aspirin and other drugs, irritating spices, and pickling fluids. In addition, genetic factors are involved in the development of ulcers. The complications of peptic ulcers are hemorrhage, perforation, and obstruction of the outlet of the stomach (pyloric stenosis) by scarring of the duodenal bulb or of the pyloric channel. A diffuse inflammation of the stomach lining, gastritis, is usually an acute process caused by contaminated food, alcohol abuse, or by bacterial- or viral-induced inflammation of the gastrointestinal tract (gastroenteritis). The other form of gastritis is gastric atrophy, in which the thickness of the mucosa is diminished. Diffuse gastric atrophy leads to partial loss of the glands and secreting cells throughout the stomach and may be associated with ironeficiency anemia.

[0017] Malignant tumors of the stomach are common and are probably a result of both genetic and environmental factors. Gastric cancer affects men more often than women and accounts for about 20 percent of all deaths from cancers of the gastrointestinal tract in the United States. Other. malignant tumors that involve the stomach are tumors ordinarily made up of lymphoid and connective tissue. Benign tumors, especially leiomyomas, are common and may, when large, cause massive hemorrhage. Polyps of the stomach are not common except in the presence of gastric atrophy.

[0018] Disorders of the Duodenum and Small Intestine

[0019] Primary cancer of the duodenum is an infrequent disease, however, benign tumors of the duodenum, particularly polyps and carcinoids, are more frequent. Cancers of the common bile duct or of the pancreas are important causes of death. A common disorder of the small intestine, distension, is caused by lack of coordination of the inner circular and outer longitudinal muscular layers of the intestinal wall which usually results in an accumulation of excess contents in the lumen. The most common cause of disturbed motility in the small intestine is food that contains an unsuitable additive, organism, or component. One of the most serious problems in small intestine are motor disturbances which arise from an intestinal obstruction that results from an actual encroachment on the bowel by an adhesive band or from an internal block produced by a tumor or gallstone. In addition, as profound an obstruction results when a portion of the intestine undergoes partial necrosis, or death, from failure of its blood supply.

[0020] The extremely common disorder known as the irritable bowel syndrome is probably due to a disturbance of the motility of the whole intestinal tract. The symptoms vary from watery diarrhea to constipation and the passage of stools with difficulty. When the colon is involved, an excess of mucus is often observed in the stools. Occasionally the irritable bowel syndrome may be due to an allergy to a particular foodstuff. The syndrome may develop following an infection such as bacillary dysentery, after which the small intestine remains irritable for many months.

[0021] A further disorder, malabsorption occurs when the small intestine is unable to transport properly broken down products of digestive materials from the lumen of the intestine into the lymphatics or mesenteric veins, where they are distributed to the rest of the body. Defects in transport occur either because the absorptive cells of the intestine lack certain enzymes, whether by birth defect or by acquired disease, or because they are hindered in their work by other disease processes that infiltrate the tissues, disturb motility, permit bacteria to overpopulate the bowel, or block the pathways over which transport normally proceeds. A malabsorption disorder of unknown cause, tropical sprue, is associated with partial atrophy of the mucosa of the small intestine. Disorders of the small intestine also include bacterial and parasitic infections.

[0022] Appendicitis is an inflammation of the vermiforin appendix that may be caused by infection or partial or total obstruction. Chronic inflammations of the small intestine include tuberculosis and regional enteritis (Crohn's disease). Celiac disease causes damage to the mucosa of the small intestine, though it is not clear whether it is caused by an immune reaction, or an inability to break down a toxic protein, gluten, to smaller peptide fractions. Studies of the immune function of those with celiac disease suggest that at least a major part of the process is a delayed hypersensitivity reaction and that the morphological changes are correlated with the presence of circulating antibodies to gluten. The mucosal reaction results in progressive atrophy, with dwarfing, if not complete disappearance, of the microvilli and villi that line the intestinal tract.

[0023] Disorders of the Large Iytestine

[0024] A wide variety of diseases and disorders occur in the large intestine. A disease that is analogous to achalasia of the esophagus is an idiopathic condition called aganglionic megacolon, or Hirschsprung's disease. It is characterized by the absence of ganglion cells and normal nerve fibres from the distal (or lower) portion of the large intestine, which results in reduced neuromuscular transmission and ceased peristalsis. The entire colon slowly becomes more and more distended and thick-walled. Abscesses in the perianal area are common complicating features of many diseases and disorders of the large intestine. Fungal and bacterial infections are also common causes of large intestine disorders.

[0025] The most common form of chronic colitis, ulcerative colitis, is idiopathic. It varies from a mild inflammation of the mucosa of the rectum, giving rise to excessive mucus and some spotting of blood in the stools, to a severe, sudden, intense illness, with destruction of a large part of the colonic mucosa, considerable blood loss, toxemia and, less commonly, perforation. The most common variety affects only the rectum and sigmoid colon and is characterized by diarrhea and the passage of mucus. Apart from the greater tendency for fistulas to form and for the wall of the intestine to thicken until the channel is obstructed, Crohn's disease is distinguishable from ulcerative colitis by microscopic findings. In Crohn's disease, the maximum damage occurs beneath the mucosa, and lymphoid conglomerations, known as granulomata, are formed in the submucosa. Crohn's disease attacks the perianal tissues more often than does ulcerative colitis. Although these two diseases are not common, they are disabling.

[0026] Tumors of the colon are usually polyps or cancers. A peculiar form of polyp is the villous adenoma, often a slowly growing, fernlike structure that spreads along the surface of the colon for some distance. Cancers compress the colonic lumen to produce obstruction, they attach to neighbouring structures to produce pain, and they perforate to give rise to peritonitis. Cancers also may metastasize to distant organs before local symptoms appear.

[0027] Anorectal disorders related to defecation are more common in the Western world than elsewhere. These disorders usually take the form of fissures (cuts or cracks in the skin or mucous membrane) at the junction of the anal mucous membrane with the slin between the thighs. Anal fistulas sometimes occur as complications of serious bowel disease, as in tuberculosis or Crohn's disease of the bowel, or in certain parasitic diseases. A more general disorder is the enlargement of veins of the rectum and anus to form external or internal hemorrhoids. Hemorrhoids protrude, are associated with anal itching and pain, and bleed, especially when they come in contact with hard stools.

[0028] Disorders of the Liver

[0029] A variety of agents, including viruses, drugs, environmental pollutants, genetic disorders, and systemic diseases, can affect the liver. The resulting disorders usually affect one of the three functional components of the liver: the hepatocyte (liver cell) itself, the bile secretory (cholangiolar) apparatus, or the blood vascular system. Most acute liver diseases are self-limited, and liver functioning returns to normal once the causes are removed or eliminated. In some cases, however, the acute disease process destroys massive areas of liver tissue in a short time, leading to extensive death (necrosis) of hepatic cells and often to death of the patient. Hepatitis may result from viral infections or toxic damage from drugs or poisons. When acute hepatitis lasts for six months or more, a slow but progressive destruction of the surrounding liver cells and bile ducts occurs, a stage called chronic active hepatitis. If hepatocellular damage is severe enough to destroy entire acini (clusters of lobules), they are often replaced with fibrous scar tissue. Bile canaliculi and hepatocytes regenerate in an irregular fashion adjacent to the scar tissue and result in a chronic condition called cirrhosis of the liver. Where inflammatory activity continues after the onset of cirrhosis, the disorderly regeneration of hepatocytes and cholangioles may lead to the development of hepatocellular or cholangiolar cancer.

[0030] Although a number of viruses affect the liver, including the cytomegalovirus of infancy and childhood and the Epstein-Barr virus of infectious mononucleosis, there are three distinctive transmissible viruses that are specifically known to cause acute damage to liver cells: hepatitis virus A (HAV), hepatitis virus B (HBV), and hepatitis virus non-A, non-B (NANB). The symptoms characteristic of the acute hepatitis caused by the HAV, HBV, and NANB viruses are essentially indistinguishable from one another.

[0031] Acute hepatitis also may be caused by the overconsumnption of alcohol or other poisons, such as comnmercial solvents (e.g., carbon tetrachloride), acetaminophen, and certain fungi. Such agents are believed to cause hepatitis when the formation of their toxic intermediate metabolites in the liver cell (phase I reactions) is beyond the capacity of the hepatocyte to conjugate, or join them with another substance for detoxification (phase II reactions) and excretion. Acute canalicular (cholestatic) hepatitis is most commonly caused by certain drugs, such as chlorpromazine, that lead to idiosyncratic reactions or, at times, by hepatitis viruses. Acute congestive liver disease usually results from the sudderi engorgement of the liver by fluids after congestive heart failure.

[0032] A prominent autoimmune liver disease is Wilson's disease, which is caused by abnormal deposits of large amounts of copper in the liver. Granulomatous hepatitis, a condition in which localized areas of inflammation (granulomas) appear in any portion of the liver lobule, is a type of inflammatory disorder associated with many systemic diseases, including tuberculosis, sarcoidosis, schistosomiasis, and certain drug reactions. Granulomatous hepatitis rarely leads to serious interference with hepatic function, although it is often chronic. The end result of many forms of chronic liver injury is cirrhosis, or scarring of liver tissue in reponse to previous acinar necrosis and irregular regeneration of liver nodules and bile ducts.

[0033] Primary biliary cirrhosis, a widespread, though uncommon, autoimnune inflammatory disease of bile ducts, is a disorder primarily affecting middle-aged and older women. Secondary biliary cirrhosis results from chronic obstruction or recurrent infection in the extrahepatic bile ducts caused by strictures, gallstones, or tumors. Infestation of the biliary tract with a liver fluke, Clonorchis sinensis, is a cause of secondary biliary cirrhosis in Asia.

[0034] Portal hypertension, the increased pressure in the portal vein and its tributaries that is the result of impediments to venous flow into the liver, is brought about by the scarring characteristic of the cirrhotic process. The increased pressure causes feeders of the portal vein to distend markedly, producing varices, or dilations of the veins. When varices are located in superficial tissues, they may rupture and bleed profusely. Two such locations are the lower esophagus and the perianal region. The accumulation of fluid in the abdominal cavity, or ascites, is related to portal hypertension, significant reduction in serum albumin, and renal retention of sodiun When albumin levels in blood are lower than normal, there is a mnarked reduction in the force that holds plasma water within the blood vessels and normally resists the effects of the intravascular pressure. The resulting increase in intravascular pressure, coupled with the increased internal pressure caused by the portal venous obstruction in the liver, leads to massive losses of plasma water into the abdominal cavity. The associated reduction of blood flow to the kidneys causes increased elaboration of the hormone aldosterone, which, in turn, causes the retention of sodium and water and a reduction in urinary output. In addition, because the movement of intestinal lymph into the liver is blocked by the cirrhotic process in the liver, the backflow of this fluid into the abdominal cavity is greatly increased. A progressive reduction in kidney function that often occurs in persons with advanced acute or chronic liver disease, hepatorenal syndrome, probably results from an inadequate perfusion of blood through the cortical (outer) portions of the kidneys, where most removal of waste products occurs. With advanced hepatocytic dysfunction, a spasm of blood vessels in the renal cortex can occur, often with good blood flow to the rest of the kidney. This spasm results in progressive failure in kidney function and often leads to death.

[0035] Although not uncommon, cancer originating in the liver, usually in hepatocytes and less frequently in cells of bile duct origin, is rare in the West and is almost always associated with active cirrhosis, particularly the form found in patients with chronic hepatitis. Long exposure to certain environmental poisons, such as vinyl chloride or carbon tetrachloride, has also been shown to lead to hepatic cancer. Cancers arising elsewhere in the body, particularly in abdominal organs, lungs, and lymphoid tissue, commonly lead to metastatic cancer in the liver and are by far the most frequent type of hepatic malignancy. Various benign types of tumors and cysts arise from certain components of the liver, such as the hepatocytes (adenomas) or blood vessels (hemangiomas). While the cause of these lesions is not always clear, hepatic adenomas are associated with the prolonged use of female sex hormones (estrogens). Benign cysts in the liver may occur as congenital defects or as the result of infections from infestation of the dog tapeworm (Echinococcus granulosus). Abscesses on the liver result from the spread of infection from the biliary tract or from other parts of the body, especially the appendix and the pelvic organs. Specific liver abscesses also result from infections with the intestinal parasite Entamoeba histolytica.

[0036] Disorders of the Biliary Tract

[0037] Cholelithiasis, or the formation of gallstones in the gallbladder, is the most common disease of the biliary tract. There are three types of Gallstones: stones containing primarily calcium bilirubinate (pigment stones); stones containing 25 percent or more of cholesterol; and stones composed of variable mixtures of both bilirubin and cholesterol (mixed gallstones). Pigment stones are the result of an increased amount of bilirubin in the liver (due to hemolytic disease) and the consequent secretion into the biliary tract of increased amounts of the water-soluble conjugate, bilirubin diglucuronide, a pigment that is normally secreted in the urine. Cholesterol and mixed cholesterol-bilirubinate stones occur when the proportion of cholesterol in bile exceeds the capacity of bile acids and lecithin to contain the total amount of cholesterol in micellar colloidal solution. Postcholecystectomy syndrome comprises painful attacks, often resembling preoperative symptoms, that occasionally occur following the surgical removal of gallstones and the gallbladder. These attacks may be related to intermittent muscular spasms of the sphincter of Oddi or of the bile ducts.

[0038] Cancer of the biliary tract is rare but may occur in almost any area, including the gallbladder, the hepatic ducts, the common bile duct, or the ampulla of Vater. In cancer of the bile duct, congenital cysts and parasitic infections, such as liver flukes, seem to lead to increased risks. Persons with extensive chronic ulcerative colitis also show a greater than normal incidence of bile duct carcinoma.

[0039] Jaundice, or yellowing of the skin, scleras, and mucous membranes, occurs whenever the level of bilirubin in the blood is significantly above normal. This condition is evident in three different types of disorders including, unconjugated, or hemolytic, jaundice; hepatocellular jaundice; and cholestatic, or obstructive jaundice. Unconjugated jaundice results when the amount of bilirubin produced from hemoglobin by the destruction of red blood cells or muscle tissue (myoglobin) overwhelms the normal capacity of the liver to transport it or when the ability of the liver to conjugate normal amounts of billrubin into billrubin diglucuronide is significantly reduced by inadequate intracellular transport or enzyme systems. Hepatocellular jaundice arises when liver cells are damaged so severely that their ability to transport bilirubin diglucuronide into the biliary system is reduced, allowing some of this yellow pigment to regurgitate into the bloodstream. Cholestatic jaundice, occurs when essentially normal liver cells are unable to transport bilirubin either through the hepatocytic-bile capillary membrane, because of damage in that area, or through the biliary tract, because of anatomical obstructions (e.g., atresias, gallstones, cancer).

[0040] Disorders of the Pancreas

[0041] Inflammation of the pancreas, or pancreatitis, is probably the most common disease of this organ. The disorder may be confined to either singular or repeated acute episodes, or it may become a chronic disease. There are many factors associated with the onset of pancreatitis, including direct injury, certain drugs, viral infections, heredity, hyperlipidernia (increased levels of blood fats), and congenital derangements of the ductal system. Localized, severe abdominal and midback pain resulting from enzyme leakage, tissue damage, and nerve irritation is the most common symptom of acute pancreatitis. In severe cases, respiratory failure, shock, and even death may occur. Chronic pancreatitis rarely follows repeated acute attacks. It seems instead to be a separate disorder that results in mucus plugs and precipitation of calcium salts in the snaller pancreatic ducts. Mucous production and plugging of the pancreas in Cystic fibrosis patients almost invariably causes destruction and scarring of the acinar tissue, usually without damaging the islets of Langerhans. A sirnilar process in the hepatic biliary system produces foci of fibrosis and bile duct proliferation, a singular form of cirrhosis.

[0042] The discovery of new human digestive system associated polynucleotides, the polypeptides encoded by them, and antibodies that immunospecifically bind these polypeptides, satisfies a need in the art by providing new compositions which are useful in detecting, preventing, diagnosing, prognosticating, treating, and/or ameliorating diseases and disorders of the digestive system, including, but not limited to, dysphagia, odynophagia, congenital disorders of the esophagus, gastric reflux, diverticula, Mallory-Weiss lesions, leiomyomas of the esophagus, lipoma, anorexia, nausea, ulcerative disease, pyloric stenosis, gastroenteritis, gastritis, gastric atropy, gastric cancer, benign tumors of the duodenum (e.g., polyps and carcinoids), pancreatic cancer, cancer of the bile duct, distension, irritable bowel syndrome, malabsorption, congenital disorders of the small intestine (e.g., Meckel's diverticulum, multiple diverticula), bacterial and parasitic infection (e.g., traveler's diarrhea, typhoid, paratyphoid, cholera, roundworms, tapeworms, amoebae, hookworms, strongyloides, threadworms, and blood flukes), megacolon (e.g., Hirschsprung's disease, aganglionic megacolon, acquired megacolon), colitis (e.g., due to bacterial, fungal, or parasitic infection, ulcerative colitis), tumors of the colon (e.g., polyps or cancers), anorectal disorders (e.g., anal fistulas, hemorrhoids, hepatitis (e.g., acute, chronic, persistent hepatitis, viral (for example, hepatitis caused by hepatitis virus A (HAV), hepatitis virus B (HBV), and hepatitis virus non-A, non-B (NANB) infection), congenital disorders of the liver (e.g., Wilson's disease, hemochromatosis, cystic fibrosis, biliary atresia, and alpha1-antitrypsin deficiency), cirrhosis, portal hypertension, cholelithiasis, cancer of the biliary tract, jaundice (e.g., unconjugated, hemolytic, hepatocellular, cholestatic, or obstructive jaundice).

[0043] The discovery of new human gastrointestinal-associated polynucleotides, the polypeptides encoded by them, and antibodies that immunospecifically bind these polypeptides, satisfies a need in the art by providing new compositions which are useful in detecting, preventing, diagnosing, prognosticating, treating, and/or ameliorating gastrointestinal-specific diseases and disorders described in more detail below.

[0044] The present invention encompasses human secreted proteins/polypeptides, and isolated nucleic acid molecules encoding said proteins/polypeptides, useful for detecting, preventing, diagnosing, prognosticating, treating, and/or ameliorating gastrointestinal diseases and disorders. Antibodies that bind these polypeptides are also encompassed by the present invention; as are vectors, host cells, and recombinant and synthetic methods for producing said polynucleotides, polypeptides, and/or antibodies. The invention further encompasses screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention also encompasses methods and compositions for inhibiting or enhancing the production and function of the polypeptides of the present invention.

Polynucleotides and Polypeptides of the Invention

[0045] Description of Table 1A

[0046] Table 1A summarizes information concerning certain polypnucleotides and polypeptides of the invention. The first column provides the gene number in the application for each clone identifier. The second column provides a unique clone identifier, “Clone ID:”, for a cDNA clone related to each contig sequence disclosed in Table 1A. Third column, the cDNA Clones identified in the second column were deposited as indicated in the third column (i.e. by ATCC Deposit No:Z and deposit date). Some of the deposits contain multiple different clones corresponding to the same gene. In the fourth column, “Vector” refers to the type of vector contained in the corresponding cDNA Clone identified in the second column. In the fifth column, the nucleotide sequence identified as “NT SEQ ID NO:X” was assembled from partially homologous (“overlapping”) sequences obtained from the corresponding cDNA clone identified in the second column and, in some cases, from additional related cDNA clones. The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X. In the sixth column, “Total NT Seq.” refers to the total number of nucleotides in the contig sequence identified as SEQ ID NO:X.” The deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as “5′ NT of Clone Seq.” (seventh column) and the “3′ NT of Clone Seq.” (eighth column) of SEQ ID NO:X. In the ninth column, the nucleotide position of SEQ ID NO:X of the putative start codon (methionine) is identified as “5′ NT of Start Codon.” Similarly, in column ten, the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as “5′ NT of First AA of Signal Pep.” In the eleventh column, the translated amino acid sequence, beginning with the methionine, is identified as “AA SEQ ID NO:Y,” although other reading frames can also be routinely translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.

[0047] In the twelfth and thirteenth columns of Table 1A, the first and last amino acid position of SEQ ID NO:Y of the predicted signal peptide is identified as “First AA of Sig Pep” and “Last AA of Sig Pep.” In the fourteenth column, the predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as “Predicted First AA of Secreted Portion”. The amino acid position of SEQ ID NO:Y of the last amino acid encoded by the open reading frame is identified in the fifteenth column as “Last AA of ORF”.

[0048] SEQ ID NO:X (where X may be any of the polynucleotide sequences disclosed in the sequence listing) and the translated SEQ ID NO:Y (where Y may be any of the polypeptide sequences disclosed in the sequence listing) are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X is useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA contained in the deposited clone. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic methods of the invention. Similarly, polypeptides identified from SEQ ID NO:Y may be used, for example, to generate antibodies which bind specifically to proteins containing the polypeptides and the secreted proteins encoded by the cDNA clones identified in Table 1A and/or elsewhere herein

[0049] 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).

[0050] 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 the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1A. The nucleotide sequence of each deposited plasmid can readily be determined by sequencing the deposited plasrnid in accordance with known methods

[0051] The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular plasmid 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.

[0052] Also provided in Table 1A is the name of the vector which contains the cDNA plasmid. Each vector is routinely used in the art. The following additional information is provided for convenience.

[0053] Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (U.S. Pat. Nos. 5,128,256 and 5,286,636), Zap Express (U.S. Pat. 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., Strategies 5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, Calif., 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

[0054] Vectors pSport1, 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, N.Y.) 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, Calif. 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, Bio/Technology 9: (1991).

[0055] The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, and/or a deposited cDNA (cDNA Clone ID). The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include, but are not limited to, preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.

[0056] 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 and SEQ ID NO:Y 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.

[0057] The present invention provides a polynucleotide comprising, or alternatively consisting of, the nucleic acid sequence of SEQ ID NO:X and/or a cDNA contained in ATCC Deposit 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, and/or a polypeptide encoded by a cDNA contained in ATCC deposit No.Z. 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 and/or a polypeptide encoded by the cDNA contained in ATCC Deposit No.Z, 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, and/or the complement of the coding strand of the cDNA contained in ATCC Deposit No.Z.

Description of Table 1B (Comprised of Tables 1B.1 and 1B.2)

[0058] Table 1B.1 and Table 1B.2 summarize some of the polynucleotides encompassed by the invention (including cDNA clones related to the sequences (Clone ID:), contig sequences (contig identifier (Contig ID:) and contig nucleotide sequence identifiers (SEQ ID NO:X)) and further summarizes certain characteristics of these polynucleotides and the polypeptides encoded thereby. The first column of Tables 1B. 1 and 1B.2 provide the gene numbers in the application for each clone identifier. The second column of Tables 1B.1 and 1B.2 provide unique clone identifiers, “Clone ID:”, for cDNA clones related to each contig sequence disclosed in Table 1A and/or Table 1B. The third column of Tables 1B.1 and 1B.2 provide unique contig identifiers, “Contig ID:” for each of the contig sequences disclosed in these tables. The fourth column of Tables 1B.1 and 1B.2 provide the sequence identifiers, “SEQ ID NO:X”, for each of the contig sequences disclosed in Table 1A and/or 1B.

[0059] Table 1B.1

[0060] The fifth column of Table 1B.1, “ORP (From-To)”, provides the location (i.e., nucleotide position numbers) within the polynucleotide sequence of SEQ ID NO:X that delineates the preferred open reading frame (ORF) that encodes the amino acid sequence shown in the sequence listing and referenced in Table 1B.1 as SEQ ID NO:Y (column 6). Column 7 of Table 1B. 1 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 PEPTIDESTRUCTTRE (Wisconsin Package v10.0Genetics Computer Group (GCG), Madison, Wis.). 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 1B.1 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 1B.1. 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 of Table 1B.1 (“Cytologic Band”) 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, 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.nhnlnih.gov/omirn/). 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 Table 1B. 1, column 9 labeled “OMIM Disease Reference(s)”. A key to the OMIM reference identification numbers is provided in Table 5.

[0061] Table 1B.2

[0062] Column 5 of Table 1B.2, “Tissue Distribution” shows the expression profile of tissue, cells, and/or cell line libraries which express the polynucleotides of the invention. The first code number shown in Table 1B.2 column 5 (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. The second number in column 5 (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 corresponding 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 ³³ P 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 tissue(s) 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.

[0063] Description of Table 1C

[0064] Table 1C summarizes additional polynucleotides encompassed by the invention (including cDNA clones related to the sequences (Clone ID:), 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:” , 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).

[0065] Description of Table 1D

[0066] Table 1D: In preferred embodiments, the present invention encompasses a method of detecting, preventing, diagnosing, prognosticating, treating, and/or ameliorating gastrointestinal diseases or disorders; comprising administering to a patient in which such treatment, prevention, or amelioration is desired a protein, nucleic acid, or antibody of the invention (or fragment or variant thereof) represented by Table 1A, Table 1B, and Table 1C, in an amount effective to detect, prevent, diagnose, prognosticate, treat, and/or ameliorate the disease or disorder.

[0067] As indicated in Table 1D, the polynucleotides, polypeptides, agonists, or antagonists of the present invention (including antibodies) can be used in assays to test for one or more biological activities. If these polynucleotides and polypeptides do exhibit activity in a particular assay, it is likely that these molecules may be involved in the diseases associated with the biological activity. Thus, the polynucleotides or polypeptides, or agonists or antagonists thereof (including antibodies) could be used to treat the associated disease.

[0068] Table 1D provides information related to biological activities for polynucleotides and polypeptides of the invention (including antibodies, agonists, and/or antagonists thereof). Table 1D also provides information related to assays which may be used to test polynucleotides and polypeptides of the invention (including antibodies, agonists, and/or antagonists thereof) for the corresponding biological activities. The first column (“Gene No.”) provides the gene number in the application for each clone identifier. The second column (“cDNA Clone ID:”) provides the unique clone identifier for each clone as previously described and indicated in Tables 1A, 1B, and 1C. The third column (“AA SEQ ID NO:Y”) indicates the Sequence Listing SEQ ID Number for polypeptide sequences encoded by the corresponding cDNA clones (also as indicated in Tables 1A, 1B, and 2). The fourth column (“Biological Activity”) indicates a biological activity corresponding to the indicated polypeptides (or polynucleotides encoding said polypeptides). The fifth column (“Exemplary Activity Assay”) further describes the corresponding biological activity and provides information pertaining to the various types of assays which may be performed to test, demonstrate, or quantify the corresponding biological activity. Table 1D describes the use of FMAT technology, inter alia, for testing or demonstrating various biological activities. Fluorometric microvolume assay technology (FMAT) is a fluorescence-based system which provides a means to perform nonradioactive cell- and bead-based assays to detect activation of cell signal transduction pathways. This technology was designed specifically for ligand binding and immunological assays. Using this technology, fluorescent cells or beads at the bottom of the well are detected as localized areas of concentrated fluorescence using a data processing system. Unbound flurophore comprising the background signal is ignored, allowing for a wide variety of homogeneous assays. FMAT technology may be used for peptide ligand binding assays, immunofluorescence, apoptosis, cytotoxicity, and bead-based immunocapture assays. See, Miraglia S et. al., “Homogeneous cell and bead based assays for highthroughput screening using flourometric microvolume assay technology,” Journal of Biomolecular Screening; 4:193-204 (1999). In particular, FMAT technology may be used to test, confirm, and/or identify the ability of polypeptides (including polypeptide fragments and variants) to activate signal transduction pathways. For example, FMAT technology may be used to test, confirm, and/or identify the ability of polypeptides to upregulate production of immunomodulatory proteins (such as, for example, interleukins, GM-CSF, Rantes, and Tumor Necrosis factors, as well as other cellular regulators (e.g. insulin)).

[0069] Table 1D also describes the use of kinase assays for testing, demonstrating, or quantifying biological activity. In this regard, the phosphorylation and de-phosphorylation of specific amino acid residues (e.g. Tyrosine, Serine, Threonine) on cell-signal transduction proteins provides a fast, reversible means for activation and de-activation of cellular signal transduction pathways. Moreover, cell signal transduction via phosphorylationlde-phosphorylation is crucial to the regulation of a wide variety of cellular processes (e.g. proliferation, differentiation, migration, apoptosis, etc.). Accordingly, kinase assays provide a powerful tool useful for testing, confirming, and/or identifying polypeptides (including polypeptide fragments and variants) that mediate cell signal transduction events via protein phosphorylation. See e.g., Forrer, P., Tamaskovic R., and Jaussi, R. “Enzyme-Linked Immunosorbent Assay for Measurement of JNK, ERK, and p38 Kinase Activities” Biol. Chem. 379(8-9): 1101-1110 (1998).

[0070] Description of Table 2

[0071] Table 2 summarizes homology and features of some of the polypeptides of the invention. The first column provides a unique clone identifier, “Clone ID:”, corresponding to a cDNA clone disclosed in Table 1A or Table 1B. The second column provides the unique contig identifier, “Contig ID:” corresponding to contigs in Table 1B and allowing for correlation with the information in Table 1B. 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 PFAMINR hit having a significant match to a polypeptide of the invention. Column six provides the accession number of the PFAMNR 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.

[0072] Description of Table 3

[0073] 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 1B. The second column provides the sequence identifier, “SEQ ID NO:X”, for contig sequences disclosed in Table 1A and/or Table 1B. The third column provides the unique contig identifier, “Contig ID:”, for contigs disclosed in Table 1B. 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 defmed 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 sequence(s) having the accession number(s) 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 sequence(s) 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).

[0074] Description of Table 4

[0075] Table 4 provides a key to the tissue/cell source identifier code disclosed. in Table 1B.2, column 5. Column 1 of Table 4 provides the tissue/cell source identifier code disclosed in Table 1B.2, Column 5. Columns 2-5 provide a description of the tissue or cell source. Note that “Description” and “Tissue” sources (i.e. columns 2 and 3) having the prefix “a_” indicates organs, tissues, or cells derived from “adult” sources. 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.

[0076] Description of Table 5

[0077] Table 5 provides a key to the OMIM reference identification numbers disclosed in Table 1B.1, column 9. OMIM reference identification numbers (Column 1) were derived from Online Mendelian Inheritance in Man (Online Mendelian Inheritance in Man, OSM. 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:flwww.ncbi.nlm.nih.gov/omim/). Column 2 provides diseases associated with the cytologic band disclosed in Table 1B. 1, column 8, as determined using the Morbid Map database.

[0078] Description of Table 6

[0079] Table 6 summarizes some of the ATCC Deposits, Deposit dates, and ATCC designation numbers of deposits made with the ATCC in connection with the present application. These deposits were made in addition to those described in the Table 1A.

[0080] Description of Table 7

[0081] Table 7 shows the cDNA libraries sequenced, and ATCC designation numbers and vector information relating to these cDNA libraries.

[0082] The first column shows the first four letters indicating the Library from which each library clone was derived. The second column indicates the catalogued tissue description for the corresponding libraries. The third column indicates the vector containing the corresponding clones. The fourth column shows the ATCC deposit designation for each libray clone as indicated by the deposit information in Table 6.

[0083] Definitions

[0084] The following definitions are provided to facilitate understanding of certain terms used throughout this specification.

[0085] 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.

[0086] In the present invention, a “secreted” protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a “mature” protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.

[0087] 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 (e.g., the polypeptide delinated in columns fourteen and fifteen of Table 1A); a nucleic acid sequence contained in SEQ ID NO:X (as described in column 5 of Table 1A and/or column 3 of Table 1B) or the complement thereof; a cDNA sequence contained in Clone ID: (as described in column 2 of Table 1A and/or Table 1B 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 (EXON From-To) of Table 1C or a fragment or variant thereof; or a nucleotide coding sequence in SEQ ID NO:B as defined in column 6 of Table 1C 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).

[0088] In the present invention, “SEQ ID NO:X” was often generated by overlapping 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 1B, each clone is identified by a cDNA Clone ID (identifier generally referred to herein as Clone ID:). 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. Table 7 provides a list of the deposited cDNA libraries. One can use the Clone ID: 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 and/or Table 1B correlates the Clone ID names with SEQ ID NO:X. Thus, starting with an SEQ ID NO:X, one can use Tables 1A, 1B, 6, 7, and 9 to determine the corresponding Clone ID, which library it came 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, Va. 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.

[0089] 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, 7.5 kb, 5 kb, 2.5 kb, 2.0, 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).

[0090] 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 7 and 8 of Table 1A or the complement thereof, the polynucleotide sequence delineated in columns 8 and 9 of Table 2 or the complement thereof, and/or cDNA sequences contained in Clone ID: (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 1C or the complement thereof. “Stringent hybridization conditions” refers to an overnight incubation at 42 degree C. in a solution comprising 50% formamide, 5×SSC (750 mM NaCl, 75 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardt's solution, 10% dextran sulfate, and 20 μ/ml Aglml denatured, sheared salmon sperm DNA, followed by washing the filters in 0.1×SSC at about 65 degree C.

[0091] 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 6×SSPE (20×SSPE=3M NaCl; 0.2M NaH₂PO₄; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 μ/ml salnon sperm blocking DNA; followed by washes at 50 degree C. with 1×SSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5×SSC).

[0092] 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, BLOTIO, 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 problerns with compatibility.

[0093] 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).

[0094] 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, enzyrnatically, or metabolically modified forms.

[0095] 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, 7.5 kb, 5 kb, 2.5 kb, 2.0 kb, or 1 kb, in 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).

[0096] “SEQ ID NO:X” refers to a polynucleotide sequence described in column 5 of Table 1A, while “SEQ ID NO:Y” refers to a polypeptide sequence described in column 10 of Table 1A. SEQ ID NO:X is identified by an integer specified in column 6 of Table 1A. The polypeptide sequence SEQ ID NO:Y is a translated open reading frame (ORF) encoded by polynucleotide SEQ ID NO:X. The polynucleotide sequences are shown in the sequence listing immediately followed by all of the polypeptide sequences. Thus, a polypeptide sequence corresponding to polynucleotide sequence SEQ ID NO:2 is the first polypeptide sequence shown in the sequence listing. The second polypeptide sequence corresponds to the polynucleotide sequence shown as SEQ ID NO:3, and so on.

[0097] 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 fiavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of 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)).

[0098] “SEQ ID NO:X” refers to a polynucleotide sequence described, for example, in Tables 1A, Table 1B, or Table 2, while “SEQ ID NO:Y” refers to a polypeptide sequence described in column 11 of Table 1A and or column 6 of Table 1B.1. SEQ ID NO:X is identified by an integer specified in column 4 of Table 1B. The polypeptide sequence SEQ ID NO:Y is a translated open reading frame (ORF) encoded by polynucleotide SEQ ID NO:X. “Clone ID:” refers to a cDNA clone described in column 2 of Table 1A and/or 1B.

[0099] “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 (e.g. activity useful in treating, preventing and/or ameliorating gastrointestinal diseases and disorders), 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.

[0100] 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 secreted polypeptides (including fragments and variants) of the invention for activity using assays as described in the examples section below.

[0101] “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 less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention).

Tables:

[0102] Table 1A

[0103] Table 1A summarizes information concerning certain polypnucleotides and polypeptides of the invention. The first column provides the gene number in the application for each clone identifier. The second column provides a unique clone identifier, “Clone ID:”, for a cDNA clone related to each contig sequence disclosed in Table 1A. Third column, the cDNA Clones identified in the second column were deposited as indicated in the third column (i.e. by ATCC Deposit No:Z and deposit date). Some of the deposits contain multiple different clones corresponding to the same gene. In the fourth column, “Vector” refers to the type of vector contained in the corresponding cDNA Clone identified in the second column. In the fifth column, the nucleotide sequence identified as “NT SEQ ID NO:X” was assembled from partially homologous (“overlapping”) sequences obtained from the corresponding cDNA clone identified in the second column and, in some cases, from additional related cDNA clones. The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X. In the sixth column, “Total NT Seq.”refers to the total number of nucleotides in the contig sequence identified as SEQ ID NO:X.”The deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as “5′ NT of Clone Seq.” (seventh column) and the “3′ NT of Clone Seq.” (eighth column) of SEQ ID NO:X. In the ninth column, the nucleotide position of SEQ ID NO:X of the putative start codon (methionine) is identified as “5′ NT of Start Codon.”Similarly , in column ten, the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as “5′ NT of First AA of Signal Pep.”In the eleventh column, the translated amino acid sequence, beginning with the methionine, is identified as “AA SEQ ID NO:Y,” although other reading frames can also be routinely translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.

[0104] In the twelfth and thirteenth columns of Table 1A, the first and last amino acid position of SEQ ID NO:Y of the predicted signal peptide is identified as “First AA of Sig Pep” and “Last AA of Sig Pep.” In the fourteenth column, the predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as “Predicted First AA of Secreted Portion”. The amino acid position of SEQ ID NO:Y of the last amino acid encoded by the open reading frame is identified in the fifteenth column as “Last AA of ORF”.

[0105] SEQ ID NO:X (where X may be any of the polynucleotide sequences disclosed in the sequence listing) and the translated SEQ ID NO:Y (where Y may be any of the polypeptide sequences disclosed in the sequence listing) are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X is useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA contained in the deposited clone. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic methods of the invention. Similarly, polypeptides identified from SEQ ID NO:Y may be used, for example, to generate antibodies which bind specifically to proteins containing the polypeptides and the secreted proteins encoded by the cDNA clones identified in Table 1A and/or elsewhere herein

[0106] 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).

[0107] 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 the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1A. The nucleotide sequence of each deposited plasmid can readily be determined by sequencing the deposited plasmid in accordance with known methods

[0108] The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular plasmid 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.

[0109] Also provided in Table 1A is the name of the vector which contains the cDNA plasmid. Each vector is routinely used in the art. The following additional information is provided for convenience.

[0110] Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (U.S. Pat. Nos. 5,128, 256 and 5,286,636), Zap Express (U.S. Pat. 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., Strategies 5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, Calif. 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

[0111] Vectors pSport1, 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, N.Y.) contains an ampicillin resistance gene and can be transformed into E. coli strain XL-1 Blue. Vector pCRO®2.1, which is available from Invitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 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., Bio/Technology 9: (1991).

[0112] The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, and/or a deposited cDNA (cDNA Clone ID). The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include, but are not limited to, preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.

[0113] 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 and SEQ ID NO:Y 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.

[0114] The present invention provides a polynucleotide comprising, or alternatively consisting of, the nucleic acid sequence of SEQ ID NO:X and/or a cDNA contained in ATCC Deposit 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, and/or a polypeptide encoded by a cDNA contained in ATCC deposit No.Z. Polynucleotides encoding a polypeptide comprising, or alternatively consisting of the polypeptide sequence of SEQ ID NO:Y, a polypeptide encoded by SEQ D NO:X and/or a polypeptide encoded by the cDNA contained in ATCC Deposit No.Z, 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, and/or the complement of the coding strand of the cDNA contained in ATCC Deposit No.Z.

TABLE 1A
									5′ NT
									of	AA	First
		ATCC		NT		5′ NT	3′ NT	5′ NT	First	SEQ	AA	Last	First	Last
		Deposit		SEQ	Total	of	of	of	AA of	ID	of	AA of	AA of	AA
Gene	cDNA	No: Z and		ID	NT	Clone	Clone	Start	Signal	NO:	Sig	Sig	Secreted	of
No.	Clone ID	Date	Vector	NO: X	Seq.	Seq.	Seq.	Codon	Pep	Y	Pep	Pep	Portion	ORF
1	H2CBU83	209889	pBluescript SK-	11	2703	1	2703	157	157	300	1	30	31	207
		May 22, 1998
1	H2CBU83	209889	pBluescript SK-	189	2709	1	2709	157	157	478	1	30	31	51
		May 22, 1998
2	H6EDC19	209324	Uni-ZAP XR	12	760	324	760	389	389	301	1	25	26	114
		Oct. 02, 1997
3	HACBD91	209626	Uni-ZAP XR	13	1445	1	1445	117	117	302	1	42	43	49
		Feb. 12, 1998
4	HAGAQ26	209368	Uni-ZAP XR	14	1333	157	1333	251	251	303	1	20	21	62
		Oct. 16, 1997
5	HAGDS35	209299	Uni-ZAP XR	15	751	1	751	45	45	304	1	23	24	122
		Sep. 25, 1997
5	HAGDS35	209299	Uni-ZAP XR	190	813	1	813	52	52	479	1	23	24	118
		Sep. 25, 1997
6	HAJAN23	PTA-322	pCMVSport 3.0	16	2849	1	2849	109	109	305	1	15	16	563
		Jul. 09, 1999
6	HAJAN23	PTA-322	pCMVSport 3.0	191	2288	1	2288	120	120	480	1	15	16	169
		Jul. 09, 1999
7	HAJBR69	209626	pCMVSport 3.0	17	755	1	755	262	262	306	1	19	20	53
		Feb. 12, 1998
8	HAMFE15	203364	pCMVSport 3.0	18	4129	1	4129	1495	1495	307	1	34	35	421
		Oct. 19, 1998
8	HAMFE15	203364	pCMVSport 3.0	192	3758	1	3758	226	226	481	1	23	24	47
		Oct. 19, 1998
9	HAMGR28	209965	pCMVSport 3.0	19	1674	47	1674	98	98	308	1	18	19	242
		Jun. 11, 1998
9	HAMGR28	209965	pCMVSport 3.0	193	1534	1	1534	40	40	482	1	18	19	203
		Jun. 11, 1998
10	HAPOM49	209878	Uni-ZAP XR	20	2005	1	2005	251	251	309	1	22	23	189
		May 18, 1998
10	HAPOM49	209878	Uni-ZAP XR	194	2664	1	2664	448	448	483	1	1	2	123
		May 18, 1998
11	HATBR65	209626	Uni-ZAP XR	21	812	1	812	252	252	310	1	16	17	64
		Feb. 12, 1998
12	HAUAI83	209626	Uni-ZAP XR	22	910	1	886	253	253	311	1	18	19	49
		Feb. 12, 1998
12	HAUAI83	209626	Uni-ZAP XR	195	1076	1	1076		575	484	1	10	11	23
		Feb. 12, 1998
13	HBAMB15	209683	pSport1	23	821	330	821	390	390	312	1	19	20	59
		Mar. 20, 1998
14	HBGBA69	209878	Uni-ZAP XR	24	981	1	981	124	124	313	1	38	39	240
		May 18, 1998
14	HBGBA69	209878	Uni-ZAP XR	196	943	1	933	62	62	485	1	38	39	60
		May 18, 1998
15	HBIAE26	209224	Uni-ZAP XR	25	1038	1	1038	75	75	314	1	18	19	39
		Aug. 28, 1997
16	HBINS58	PTA-885	pCMVSport 3.0	26	843	1	843	57	57	315	1	30	31	174
		Oct. 28, 1999
16	HBINS58	PTA-885	pCMVSport 3.0	197	1566	1	1566	71	71	486	1	29	30	173
		Oct. 28, 1999
16	HBINS58	PTA-885	pCMVSport 3.0	198	1067	1	1067	100	100	487	1	29	30	210
		Oct. 28, 1999
17	HBNAW17	209242	Uni-ZAP XR	27	601	1	601	77	77	316	1	37	38	61
		Sep. 12, 1997
18	HCE2F54	209626	Uni-ZAP XR	28	1276	19	1256	166	166	317	1	19	20	319
		Feb. 12, 1998
19	HCE3G69	209878	Uni-ZAP XR	29	2084	1	2084	165	165	318	1	19	20	336
		May 18, 1998
19	HCE3G69	209878	Uni-ZAP XR	199	2078	1	2078	165	165	488	1	19	20	105
		May 18, 1998
20	HCE5F43	209580	Uni-ZAP XR	30	1765	1	1765	113	113	319	1	20	21	272
		Jan. 14, 1998
21	HCEFB80	PTA-2069	Uni-ZAP XR	31	2494	1	2494	12	12	320	1	35	36	89
		Jun. 09, 2000
21	HCEFB80	PTA-2069	Uni-ZAP XR	200	2494	1	2451	5	5	489	1	35	36	89
		Jun. 09, 2000
22	HCEWE20	209300	Uni-ZAP XR	32	885	13	885	166	166	321	1	18	19	51
		Sep. 25, 1997
23	HCGMD59	209627	pCMVSport 2.0	33	790	1	780	438	438	322	1	30	31	74
		Feb. 12, 1998
24	HCNDR47	PTA-855	Lambda ZAP II	34	1343	1	1343	21	21	323	1	24	25	127
		Oct. 18, 1999
24	HCNDR47	PTA-855	Lambda ZAP II	201	845	1	845	124	124	490	1	47	48	127
		Oct. 18, 1999
24	HCNDR47	PTA-855	Lambda ZAP II	202	738	1	738		603	491	1	8	9	9
		Oct. 18, 1999
25	HCNSM70	209580	pBluescript	35	1089	1	1089	107	107	324	1	26	27	215
		Jan. 14, 1998
25	HCNSM70	209580	pBluescript	203	1145	62	1145	161	161	492	1	26	27	91
		Jan. 14, 1998
26	HCUIM65	209324	ZAP Express	36	875	331	736	557	557	325	1	27	28	47
		Oct. 02, 1997
27	HCWDS72	209852	ZAP Express	37	320	1	320	19	19	326	1	17	18	100
		May 07, 1998
28	HCWKC15	209324	ZAP Express	38	710	1	710	37	37	327	1	18	19	40
		Oct. 02, 1997
29	HDHEB60	209215	pCMVSport 2.0	39	1421	235	1421	568	568	328	1	24	25	108
		Aug. 21, 1997
30	HDPBA28	PTA-163	pCMVSport 3.0	40	3447	197	3447	259	259	329	1	32	33	941
		Jun. 01, 1999
30	HDPBA28	PTA-163	pCMVSport 3.0	204	4909	1	4909	69	69	493	1	32	33	941
		Jun. 01, 1999
31	HDPCL63	PTA-1544	pCMVSport 3.0	41	3037	115	3037	35	35	330	1	58	59	267
		Mar. 21, 2000
31	HDPCL63	PTA-1544	pCMVSport 3.0	205	2921	1	2921	260	260	494	1	17	18	157
		Mar. 21, 2000
31	HDPCL63	PTA-1544	pCMVSport 3.0	206	1259	358	1259		605	495	1	6	7	118
		Mar. 21, 2000
32	HDPCO25	209125	pCMVSport 3.0	42	767	76	767	182	182	331	1	20	21	53
		Jun. 19, 1997
33	HDPFP29	209626	pCMVSport 3.0	43	1057	1	1057	293	293	332	1	30	31	52
		Feb. 12, 1998
34	HDPGT01	203027	pCMVSport 3.0	44	2687	138	2687	8	8	333	1	28	29	87
		Jun. 26, 1998
35	HDPHI51	209125	pCMVSport 3.0	45	728	1	728	245	245	334	1	30	31	40
		Jun. 19, 1997
36	HDPJM30	209563	pCMVSport 3.0	46	1635	308	1633	59	59	335	1	59	60	525
		Dec. 18, 1997
36	HDPJM30	209563	pCMVSport 3.0	207	1314	1	1313	259	259	496	1	20	21	59
		Dec. 18, 1997
37	HDPMM88	PTA-848	pCMVSport 3.0	47	4893	1	4893	100	100	336	1	37	38	937
		Oct. 13, 1999
37	HDPMM88	PTA-848	pCMVSport 3.0	208	468	1	468	141	141	497	1	20	21	109
		Oct. 13, 1999
37	HDPMM88	PTA-848	pCMVSport 3.0	209	181	1	181		44	498	1	7	8	46
		Oct. 13, 1999
37	HDPMM88	PTA-848	pCMVSport 3.0	210	612	1	612		419	499	1			6
		Oct. 13, 1999
37	HDPMM88	PTA-848	pCMVSport 3.0	211	1024	1	1024		111	500	1	5	6	11
		Oct. 13, 1999
37	HDPMM88	PTA-848	pCMVSport 3.0	212	366	18	321		167	501	1	1	2	56
		Oct. 13, 1999
37	HDPMM88	PTA-848	pCMVSport 3.0	213	519	1	519		28	502	1	1	2	53
		Oct. 13, 1999
38	HDPOJ08	209878	pCMVSport 3.0	48	1655	1	1655	159	159	337	1	18	19	122
		May 18, 1998
39	HDPPN86	PTA-867	pCMVSport 3.0	49	6297	1	6297	127	127	338	1	32	33	46
		Oct. 26, 1999
39	HDPPN86	PTA-867	pCMVSport 3.0	214	2042	1	2042	117	117	503	1	26	27	46
		Oct. 26, 1999
40	HDPSB18	PTA-868	pCMVSport 3.0	50	3408	1	3408	123	123	339	1	18	19	66
		Oct. 26, 1999
40	HDPSB18	PTA-868	pCMVSport 3.0	215	308	1	308		116	504	1	17	18	64
		Oct. 26, 1999
40	HDPSB18	PTA-868	pCMVSport 3.0	216	1568	1	1568		1525	505	1	7	8	14
		Oct. 26, 1999
40	HDPSB18	PTA-868	pCMVSport 3.0	217	865	1	865		345	506	1	1	2	107
		Oct. 26, 1999
41	HDPSH53	PTA-868	pCMVSport 3.0	51	1663	1	1663	158	158	340	1	19	20	90
		Oct. 26, 1999
41	HDPSH53	PTA-868	pCMVSport 3.0	218	1687	1	1687	153	153	507	1	19	20	127
		Oct. 26, 1999
41	HDPSH53	PTA-868	pCMVSport 3.0	219	570	1	570	212	212	508	1	19	20	90
		Oct. 26, 1999
42	HDPSP01	209745	pCMVSport 3.0	52	2343	1	2343	184	184	341	1	20	21	710
		Apr. 07, 1998
42	HDPSP01	209745	pCMVSport 3.0	220	1752	1	1752	227	227	509	1	20	21	308
		Apr. 07, 1998
43	HDPSP54	209782	pCMVSport 3.0	53	3091	2304	3091	2356	2356	342	1	18	19	48
		Apr. 20, 1998
43	HDPSP54	209782	pCMVSport 3.0	221	536	1	536	179	179	510	1	41	42	55
		Apr. 20, 1998
44	HDPUW68	203331	pCMVSport 3.0	54	1748	1	1748	40	40	343	1	18	19	467
		Oct. 08, 1998
45	HDPXY01	PTA-868	pCMVSport 3.0	55	766	1	766	23	23	344	1	37	38	98
		Oct. 26, 1999
45	HDPXY01	PTA-868	pCMVSport 3.0	222	2409	1	2409	33	33	511	1	37	38	98
		Oct. 26, 1999
45	HDPXY01	PTA-868	pCMVSport 3.0	223	737	1	423		539	512	1	9	10	22
		Oct. 26, 1999
45	HDPXY01	PTA-868	pCMVSport 3.0	224	1471	105	1471		1190	513	1	16	17	25
		Oct. 26, 1999
46	HDTBD53	PTA-848	pCMVSport 2.0	56	2803	1	2803	288	288	345	1	22	23	365
		Oct. 13, 1999
46	HDTBD53	PTA-848	pCMVSport 2.0	225	3302	1	2718	292	292	514	1	22	23	365
		Oct. 13, 1999
47	HDTBV77	203070	pCMVSport 2.0	57	2181	1	2181	326	326	346	1	22	23	608
		Jul. 27, 1998
48	HDTDQ23	209965	pCMVSport 2.0	58	2207	1	2207	132	132	347	1	20	21	56
		Jun. 11, 1998
48	HDTDQ23	209965	pCMVSport 2.0	226	2227	1	2206	148	148	515	1	20	21	108
		Jun. 11, 1998
48	HDTDQ23	209965	pCMVSport 2.0	227	2214	1	2206	148	148	516	1	20	21	73
		Jun. 11, 1998
49	HE2DE47	97923	Uni-ZAP XR	59	3533	2821	3532	808	808	348	1	30	31	540
		Mar. 07, 1997
		209071
		May 22, 1997
49	HE2DE47	97923	Uni-ZAP XR	228	1145	435	1115	515	515	517	1	22	23	81
		Mar. 07, 1997
		209071
		May 22, 1997
50	HE2NV57	209877	Uni-ZAP XR	60	867	1	867	99	99	349	1	36	37	99
		May 18, 1998
51	HE2PH36	209603	Uni-ZAP XR	61	1558	1	1558	28	28	350	1	21	22	66
		Jan. 29, 1998
52	HE8DS15	PTA-1544	Uni-ZAP XR	62	2199	1	2199	91	91	351	1	24	25	72
		Mar. 21, 2000
53	HE9HY07	209010	Uni-ZAP XR	63	832	1	832	35	35	352	1	26	27	41
		Apr. 28, 1997
		209085
		May 29, 1997
54	HEOMQ63	209563	pSport1	64	1336	1	1336	123	123	353	1	23	24	47
		Dec. 18, 1997
55	HEPAB80	209423	Uni-ZAP XR	65	799	1	799	73	73	354	1	28	29	121
		Oct. 30, 1997
55	HEPAB80	209423	Uni-ZAP XR	229	802	1	802	67	67	518	1	28	29	122
		Oct. 30, 1997
56	HFABH95	209407	Uni-ZAP XR	66	1347	1	1347	199	199	355	1	21	22	116
		Oct. 23, 1997
57	HFAEF57	209277	Uni-ZAP XR	67	642	1	642	232	232	356	1	42	43	86
		Sep. 18, 1997
58	HFCEB37	209008	Uni-ZAP XR	68	802	352	802		487	357	1			10
		Apr. 28, 1997
		209084
		May 29, 1997
59	HFFAD59	209242	Lambda ZAP II	69	470	1	470	44	44	358	1	17	18	45
		Sep. 12, 1997
60	HFGAD82	209225	Uni-ZAP XR	70	1881	772	1861	1019	1019	359	1	18	19	38
		Aug. 28, 1997
61	HFIUR10	209277	pSport1	71	541	1	541	50	50	360	1	22	23	44
		Sep. 18, 1997
62	HFTBM50	209300	Uni-ZAP XR	72	762	1	740	158	158	361	1	20	21	34
		Sep. 25, 1997
63	HFTDZ36	209300	Uni-ZAP XR	73	1103	231	1103	547	547	362	1	22	23	68
		Sep. 25, 1997
64	HFXBL33	203071	Lambda ZAP II	74	1633	1	1633	152	152	363	1	24	25	162
		Jul. 27, 1998
65	HFXJX44	209782	Lambda ZAP II	75	1384	1	1384	98	98	364	1	18	19	47
		Apr. 20, 1998
66	HFXKT05	209651	Lambda ZAP II	76	1715	1	1715	204	204	365	1	18	19	79
		Mar. 04, 1998
67	HGBHI35	209423	Uni-ZAP XR	77	1437	71	1276	87	87	366	1	16	17	292
		Oct. 30, 1997
68	HGLAF75	209407	Uni-ZAP XR	78	776	1	776	231	231	367	1	28	29	121
		Oct. 23, 1997
69	HHENV10	209368	pCMVSport 3.0	79	1155	1	1155	143	143	368	1	27	28	50
		Oct. 16, 1997
70	HHGCG53	97899	Lambda ZAP II	80	407	1	407	230	230	369	1	33	34	44
		Feb. 26, 1997
		209045
		May 15, 1997
71	HHGCM76	97958	Lambda ZAP II	81	711	8	711	270	270	370	1	22	23	89
		Mar. 13, 1997
		209072
		May 22, 1997
71	HHGCM76	97958	Lambda ZAP II	230	711	8	711	270	270	519	1			11
		Mar. 13, 1997
		209072
		May 22, 1997
72	HHPEN62	209746	Uni-ZAP XR	82	2152	141	2152	183	183	371	1	27	28	508
		Apr. 07, 1998
73	HJABB94	209119	pBluescript SK-	83	1555	1	1555	74	74	372	1	28	29	77
		Jun. 12, 1997
74	HJACG30	PTA-843	pBluescript SK-	84	1532	1	1532	291	291	373	1	27	28	44
		Oct. 13, 1999
74	HJACG30	PTA-843	pBluescript SK-	231	1614	1020	1614		50	520	1	1	2	130
		Oct. 13, 1999
74	HJACG30	PTA-843	pBluescript SK-	232	1087	491	1087		350	521	1	1	2	122
		Oct. 13, 1999
75	HJBCY35	209877	pBluescript SK-	85	1559	93	1272	232	232	374	1	23	24	327
		May 18, 1998
76	HJPAD75	209641	Uni-ZAP XR	86	1231	1	1231	60	60	375	1	29	30	91
		Feb. 25, 1998
77	HKABZ65	209683	pCMVSport 2.0	87	1189	1	1189	77	77	376	1	17	18	243
		Mar. 20, 1998
77	HKABZ65	209683	pCMVSport 2.0	233	1191	1	1191	69	69	522	1	17	18	243
		Mar. 20, 1998
78	HKACB56	209346	pCMVSport 2.0	88	496	1	496	27	27	377	1	23	24	80
		Oct. 09, 1997
79	HKACD58	209346	pCMVSport 2.0	89	3153	1	3153	38	38	378	1	25	26	301
		Oct. 09, 1997
79	HKACD58	209346	pCMVSport 2.0	234	1626	1	1626	35	35	523	1	25	26	154
		Oct. 09, 1997
80	HKAEV06	209627	pCMVSport 2.0	90	2496	1	2496	501	501	379	1	30	31	438
		Feb. 12, 1998
80	HKAEV06	209627	pCMVSport 2.0	235	2351	1	2351	197	197	524	1	29	30	57
		Feb. 12, 1998
81	HKAFT66	PTA-849	pCMVSport 2.0	91	1001	270	1001	508	508	380	1	41	42	107
		Oct. 13, 1999
81	HKAFT66	PTA-849	pCMVSport 2.0	236	1001	270	1001	508	508	525	1	41	42	107
		Oct. 13, 1999
81	HKAFT66	PTA-849	pCMVSport 2.0	237	669	1	669	234	234	526	1			37
		Oct. 13, 1999
82	HKB1E57	209651	pCMVSport 1	92	1142	1038	1142	178	178	381	1	30	31	234
		Mar. 04, 1998
82	HKB1E57	209651	pCMVSport 1	238	417	1	417	30	30	527	1	26	27	46
		Mar. 04, 1998
83	HKFBC53	209782	ZAP Express	93	2238	1	2238	64	64	382	1	15	16	470
		Apr. 20, 1998
83	HKFBC53	209782	ZAP Express	239	1949	1	1906	41	41	528	1	18	19	442
		Apr. 20, 1998
83	HKFBC53	209782	ZAP Express	240	1487	1	1487		3	529	1	1	2	309
		Apr. 20, 1998
83	HKFBC53	209782	ZAP Express	241	1525	1	1525		3	530	1	1	2	243
		Apr. 20, 1998
84	HKGDL36	209877	pSport1	94	1052	1	1052	53	53	383	1	33	34	260
		May 18, 1998
84	HKGDL36	209877	pSport1	242	1050	1	1050	55	55	531	1	33	34	148
		May 18, 1998
85	HKISB57	209603	pBluescript	95	1492	1	1439	130	130	384	1	19	20	95
		Jan. 29, 1998
86	HKMLM11	209236	pBluescript	96	954	1	954	82	82	385	1	20	21	130
		Sep. 04, 1997
87	HKMMW74	209463	pBluescript	97	1794	1	1794	202	202	386	1	21	22	41
		Nov. 14, 1997
88	HLDON23	209628	pCMVSport 3.0	98	1262	208	1256	368	368	387	1	20	21	113
		Feb. 12, 1998
89	HLDQR62	203027	pCMVSport 3.0	99	2572	427	2572	520	520	388	1	18	19	161
		Jun. 26, 1998
90	HLDQU79	203071	pCMVSport 3.0	100	1488	1	1488	99	99	389	1	23	24	348
		Jul. 27, 1998
91	HLHAL68	209746	Uni-ZAP XR	101	704	1	704	30	30	390	1	21	22	44
		Apr. 07, 1998
92	HLIBD68	203071	pCMVSport 1	102	1022	1	1022	186	186	391	1	35	36	50
		Jul. 27, 1998
93	HLICQ90	203517	pCMVSport 1	103	1766	1	1766	249	249	392	1	29	30	206
		Dec. 10, 1998
94	HLTHR66	209782	Uni-ZAP XR	104	2286	1	2286	5	5	393	1	34	35	75
		Apr. 20, 1998
95	HLTIP94	PTA-2076	Uni-ZAP XR	105	1240	1	1170	226	226	394	1	26	27	97
		Jun. 09, 2000
95	HLTIP94	PTA-2076	Uni-ZAP XR	243	647	1	647	226	226	532	1	26	27	65
		Jun. 09, 2000
95	HLTIP94	PTA-2076	Uni-ZAP XR	244	1321	870	1209		3	533	1	1	2	299
		Jun. 09, 2000
96	HLWAA17	209626	pCMVSport 3.0	106	997	246	997	436	436	395	1	15	16	187
		Feb. 12, 1998
97	HLYAC95	203071	pSport1	107	312	1	312	92	92	396	1	16	17	46
		Jul. 27, 1998
98	HMADK33	209368	Uni-ZAP XR	108	864	1	864	161	161	397	1	24	25	152
		Oct. 16, 1997
99	HMAMI15	PTA-2075	Uni-ZAP XR	109	1258	1	1258	4	4	398	1	26	27	340
		Jun. 09, 2000
99	HMAMI15	PTA-2075	Uni-ZAP XR	245	1084	1	1084	3	3	534	1	26	27	306
		Jun. 09, 2000
100	HMCFY13	209628	Uni-ZAP XR	110	883	1	883	175	175	399	1	27	28	64
		Feb. 12, 1998
101	HMDAB56	209368	Uni-ZAP XR	111	1465	1	1465	273	273	400	1	32	33	44
		Oct. 16, 1997
102	HMEED18	209368	Lambda ZAP II	112	1369	28	1369	34	34	401	1	34	35	221
		Oct. 16, 1997
103	HMEFT54	209243	Lambda ZAP II	113	596	1	596	332	332	402	1	19	20	39
		Sep. 12, 1997
104	HMEGF92	209243	Lambda ZAP II	114	629	1	611	92	92	403	1	27	28	62
		Sep. 12, 1997
105	HMSDL37	PTA-842	Uni-ZAP XR	115	2497	1	2497	531	531	404	1	26	27	64
		Oct. 13, 1999
105	HMSDL37	PTA-842	Uni-ZAP XR	246	1776	1	1776	528	528	535	1	26	27	64
		Oct. 13, 1999
105	HMSDL37	PTA-842	Uni-ZAP XR	247	784	1	784	565	565	536	1	6	7	26
		Oct. 13, 1999
105	HMSDL37	PTA-842	Uni-ZAP XR	248	699	275	427		2	537	1	1	2	50
		Oct. 13, 1999
106	HMSFI26	209368	Uni-ZAP XR	116	1217	1	1217	120	120	405	1	34	35	62
		Oct. 16, 1997
107	HMVBS81	209628	pSport1	117	529	1	529	34	34	406	1	43	44	139
		Feb. 12, 1998
108	HMWDC28	209126	Uni-ZAP XR	118	1146	105	754	124	124	407	1	30	31	42
		Jun. 19, 1997
109	HMWFT65	209368	Uni-ZAP XR	119	1346	1	1346	72	72	408	1	27	28	121
		Oct. 16, 1997
110	HNEEE24	209346	Uni-ZAP XR	120	1079	1	1079	213	213	409	1	21	22	71
		Oct. 09, 1997
111	HNFFC43	203027	Uni-ZAP XR	121	2103	209	2058	488	488	410	1	12	13	68
		Jun. 26, 1998
112	HNFIY77	209628	pBluescript	122	1212	28	1212	228	228	411	1	34	35	233
		Feb. 12, 1998
113	HNFJF07	209463	Uni-ZAP XR	123	616	1	616	86	86	412	1	21	22	66
		Nov. 14, 1997
114	HNGFR31	209407	Uni-ZAP XR	124	536	1	536	108	108	413	1	23	24	90
		Oct. 23, 1997
115	HNGIJ31	209236	Uni-ZAP XR	125	796	1	796	135	135	414	1	16	17	36
		Sep. 04, 1997
116	HNGJE50	209368	Uni-ZAP XR	126	1037	1	1037	77	77	415	1	36	37	46
		Oct. 16, 1997
117	HNGND37	203648	Uni-ZAP XR	127	841	1	841	388	388	416	1	27	28	82
		Feb. 09, 1999
118	HNGOI12	PTA-847	Uni-ZAP XR	128	2128	1	2128	27	27	417	1	34	35	57
		Oct. 13, 1999
118	HNGOI12	PTA-847	Uni-ZAP XR	249	774	1	774	27	27	538	1	34	35	57
		Oct. 13, 1999
118	HNGOI12	PTA-847	Uni-ZAP XR	250	1396	1	1396		596	539	1	25	26	93
		Oct. 13, 1999
119	HNHEU93	209628	Uni-ZAP XR	129	748	1	748	57	57	418	1	34	35	81
		Feb. 12, 1998
120	HNHFM14	209683	Uni-ZAP XR	130	297	1	297	38	38	419	1	28	29	80
		Mar. 20, 1998
121	HNHNB29	PTA-623	Uni-ZAP XR	131	1894	1	1894	40	40	420	1	20	21	53
		Sep. 02, 1999
122	HNHOD46	PTA-1543	Uni-ZAP XR	132	1355	1	1355	12	12	421	1	20	21	80
		Mar. 21, 2000
123	HNTBI26	209563	pCMVSport 3.0	133	1382	1	1382	28	28	422	1	35	36	320
		Dec. 18, 1997
123	HNTBI26	209563	pCMVSport 3.0	251	1397	1	1397	32	32	540	1	35	36	172
		Dec. 18, 1997
123	HNTBI26	209563	pCMVSport 3.0	252	1368	1	1368	16	16	541	1	35	36	131
		Dec. 18, 1997
124	HNTBL27	209324	pCMVSport 3.0	134	791	71	791	100	100	423	1	23	24	115
		Oct. 02, 1997
125	HNTCE26	PTA-1544	pCMVSport 3.0	135	2163	830	2163	111	111	424	1	30	31	402
		Mar. 21, 2000
125	HNTCE26	PTA-1544	pCMVSport 3.0	253	1763	1	1763	57	57	542	1	28	29	121
		Mar. 21, 2000
126	HNTNI01	209782	pSport1	136	2087	1	2087	307	307	425	1	33	34	76
		Apr. 20, 1998
126	HNTNI01	209782	pSport1	254	1274	1	1114	306	306	543	1	33	34	49
		Apr. 20, 1998
127	HODDF13	203069	Uni-ZAP XR	137	830	1	830	46	46	426	1	23	24	41
		Jul. 27, 1998
128	HODDN92	209012	Uni-ZAP XR	138	1939	294	1939		434	427	1	26	27	35
		Apr. 28, 1997
		209089
		Jun. 05, 1997
129	HOFMQ33	PTA-848	pCMVSport 2.0	139	2410	1	2410	49	49	428	1	24	25	484
		Oct. 13, 1999
129	HOFMQ33	PTA-848	pCMVSport 2.0	255	2409	1	2409	48	48	544	1	24	25	484
		Oct. 13, 1999
129	HOFMQ33	PTA-848	pCMVSport 2.0	256	876	1	876	78	78	545	1	24	25	266
		Oct. 13, 1999
129	HOFMQ33	PTA-848	pCMVSport 2.0	257	1586	1	1586		724	546	1			5
		Oct. 13, 1999
129	HOFMQ33	PTA-848	pCMVSport 2.0	258	1011	873	1011		123	547	1	1	2	84
		Oct. 13, 1999
130	HOFOC73	PTA-848	pCMVSport 2.0	140	1491	1	1491	18	18	429	1	18	19	129
		Oct. 13, 1999
130	HOFOC73	PTA-848	pCMVSport 2.0	259	1395	1	1395	23	23	548	1	18	19	67
		Oct. 13, 1999
130	HOFOC73	PTA-848	pCMVSport 2.0	260	270	1	270		127	549	1	4	5	14
		Oct. 13, 1999
130	HOFOC73	PTA-848	pCMVSport 2.0	261	2324	662	2324	142	142	550	1			6
		Oct. 13, 1999
131	HOQBJ82	PTA-845	Uni-ZAP XR	141	3530	1	3530	361	361	430	1	21	22	164
		Oct. 13, 1999
131	HOQBJ82	PTA-845	Uni-ZAP XR	262	585	64	585	102	102	551	1	24	25	161
		Oct. 13, 1999
131	HOQBJ82	PTA-845	Uni-ZAP XR	263	4344	1339	1942		55	552	1	1	2	325
		Oct. 13, 1999
132	HOSBY40	209551	Uni-ZAP XR	142	1145	1	1145	89	89	431	1	30	31	56
		Dec. 12, 1997
133	HOSDJ25	209423	Uni-ZAP XR	143	2214	985	2214	1076	1076	432	1	18	19	40
		Oct. 30, 1997
133	HOSDJ25	209423	Uni-ZAP XR	264	1258	1	1258	146	146	553	1	18	19	40
		Oct. 30, 1997
134	HPEAD79	209244	Uni-ZAP XR	144	813	1	813	51	51	433	1	15	16	41
		Sep. 12, 1997
135	HPIBO15	209563	Uni-ZAP XR	145	1739	1	1739	128	128	434	1	18	19	211
		Dec. 18, 1997
135	HPIBO15	209563	Uni-ZAP XR	265	1739	1	1739	127	127	554	1	18	19	173
		Dec. 18, 1997
136	HPJBI33	209889	Uni-ZAP XR	146	1677	1	1677	236	236	435	1	31	32	53
		May 22, 1998
137	HPJBK12	PTA-855	Uni-ZAP XR	147	2648	1	2648	126	126	436	1	18	19	48
		Oct. 18, 1999
137	HPJBK12	PTA-855	Uni-ZAP XR	266	538	1	538	119	119	555	1	18	19	48
		Oct. 18, 1999
137	HPJBK12	PTA-855	Uni-ZAP XR	267	1346	1	1346		969	556	1			10
		Oct. 18, 1999
137	HPJBK12	PTA-855	Uni-ZAP XR	268	912	1	912	509	509	557	1			4
		Oct. 18, 1999
138	HPMDK28	209628	Uni-ZAP XR	148	1084	1	1084	64	64	437	1	25	26	201
		Feb. 12, 1998
138	HPMDK28	209628	Uni-ZAP XR	269	1177	1	1083	58	58	558	1	25	26	201
		Feb. 12, 1998
139	HPRAL78	209195	Uni-ZAP XR	149	2072	1	2072	62	62	438	1	29	30	420
		Aug. 01, 1997
139	HPRAL78	209195	Uni-ZAP XR	270	1775	1038	1775	70	70	559	1	29	30	392
		Aug. 01, 1997
139	HPRAL78	209195	Uni-ZAP XR	271	866	128	866	148	148	560	1	42	43	63
		Aug. 01, 1997
140	HRABA80	209889	pCMVSport 3.0	150	1251	1	1251	144	144	439	1	27	28	102
		May 22, 1998
140	HRABA80	209889	pCMVSport 3.0	272	1237	1	1237	130	130	561	1	27	28	102
		May 22, 1998
141	HRACD15	209852	pCMVSport 3.0	151	1539	24	1539	252	252	440	1	40	41	53
		May 07, 1998
141	HRACD15	209852	pCMVSport 3.0	273	1681	24	1453	252	252	562	1	40	41	53
		May 07, 1998
142	HRACJ35	209878	pCMVSport 3.0	152	2077	1	2077	132	132	441	1	24	25	472
		May 18, 1998
142	HRACJ35	209878	pCMVSport 3.0	274	1863	8	1863	99	99	563	1	24	25	472
		May 18, 1998
142	HRACJ35	209878	pCMVSport 3.0	275	1134	1	1134		1	564	1	1	2	178
		May 18, 1998
143	HRGBL78	PTA-841	Uni-ZAP XR	153	2108	1	2108	30	30	442	1	27	28	359
		Oct. 13, 1999
143	HRGBL78	PTA-841	Uni-ZAP XR	276	626	8	626	30	30	565	1	38	39	199
		Oct. 13, 1999
143	HRGBL78	PTA-841	Uni-ZAP XR	277	152	1	152		11	566	1			2
		Oct. 13, 1999
143	HRGBL78	PTA-841	Uni-ZAP XR	278	1760	127	1760		1048	567	1	10	11	32
		Oct. 13, 1999
144	HROAJ39	PTA-2069	Uni-ZAP XR	154	1146	224	1146	10	10	443	1	30	31	379
		Jun. 09, 2000
144	HROAJ39	PTA-2069	Uni-ZAP XR	279	880	1	880	31	31	568	1	15	16	283
		Jun. 09, 2000
144	HROAJ39	PTA-2069	Uni-ZAP XR	280	1106	224	1106	247	247	569	1	15	16	286
		Jun. 09, 2000
145	HROBD68	203499	Uni-ZAP XR	155	1998	1	1998	122	122	444	1	22	23	48
		Dec. 01, 1998
146	HSAWD74	209126	Uni-ZAP XR	156	970	106	970	142	142	445	1	26	27	142
		Jun. 19, 1997
146	HSAWD74	209126	Uni-ZAP XR	281	646	1	646	122	122	570	1	29	30	45
		Jun. 19, 1997
147	HSDEK49	209603	Uni-ZAP XR	157	1782	1	1782	60	60	446	1	19	20	399
		Jan. 29, 1998
147	HSDEK49	209603	Uni-ZAP XR	282	1590	96	1590	126	126	571	1	21	22	305
		Jan. 29, 1998
148	HSDFJ26	203648	Uni-ZAP XR	158	1205	23	1179	99	99	447	1	20	21	223
		Feb. 09, 1999
148	HSDFJ26	203648	Uni-ZAP XR	283	1179	1	1179	99	99	572	1	19	20	72
		Feb. 09, 1999
149	HSDSB09	209145	pBluescript	159	809	1	809	16	16	448	1	17	18	135
		Jul. 17, 1997
149	HSDSB09	209145	pBluescript	284	819	1	819	22	22	573	1	17	18	121
		Jul. 17, 1997
150	HSDSE75	209324	pBluescript	160	1151	1	1151	160	160	449	1	18	19	181
		Oct. 02, 1997
151	HSIDJ81	209551	Uni-ZAP XR	161	1303	1	1303	8	8	450	1	22	23	58
		Dec. 12, 1997
152	HSKDA27	PTA-322	Uni-ZAP XR	162	4412	1	4412	786	786	451	1	24	25	950
		Jul. 09, 1999
152	HSKDA27	PTA-322	Uni-ZAP XR	285	1792	134	1792	127	127	574	1	21	22	509
		Jul. 09, 1999
152	HSKDA27	PTA-322	Uni-ZAP XR	286	1673	1	1673	12	12	575	1	21	22	554
		Jul. 09, 1999
153	HSKGN81	97977	pBluescript	163	1907	151	1432	353	353	452	1	23	24	260
		Apr. 04, 1997
		209082
		May 29, 1997
153	HSKGN81	97977	pBluescript	287	2084	335	2084	537	537	576	1	18	19	23
		Apr. 04, 1997
		209082
		May 29, 1997
154	HSNAD72	209139	Uni-ZAP XR	164	861	1	861	220	220	453	1	19	20	35
		Jul. 03, 1997
155	HSNMC45	209300	Uni-ZAP XR	165	587	1	587	225	225	454	1	18	19	55
		Sep. 25, 1997
155	HSNMC45	209300	Uni-ZAP XR	288	720	1	720	232	232	577	1	17	18	25
		Sep. 25, 1997
156	HSQFP66	209126	Uni-ZAP XR	166	477	1	477	96	96	455	1	32	33	78
		Jun. 19, 1997
157	HSRFZ57	PTA-622	Uni-ZAP XR	167	1930	1	1925	82	82	456	1	18	19	41
		Sep. 02, 1999
158	HSUBW09	209007	Uni-ZAP XR	168	1021	1	1021	153	153	457	1	31	32	56
		Apr. 28, 1997
		209083
		May 29, 1997
159	HSVBU91	209603	Uni-ZAP XR	169	727	1	727	256	256	458	1	18	19	90
		Jan. 29, 1998
160	HTAEE28	PTA-843	Uni-ZAP XR	170	1341	1	1341	319	319	459	1	33	34	282
		Oct. 13, 1999
160	HTAEE28	PTA-843	Uni-ZAP XR	289	738	159	738	372	372	578	1	33	34	122
		Oct. 13, 1999
160	HTAEE28	PTA-843	Uni-ZAP XR	290	935	1	807		124	579	1	1	2	216
		Oct. 13, 1999
161	HTECC05	209877	Uni-ZAP XR	171	839	1	839	13	13	460	1	15	16	178
		May 18, 1998
161	HTECC05	209877	Uni-ZAP XR	291	871	1	871	21	21	580	1	15	16	127
		May 18, 1998
161	HTECC05	209877	Uni-ZAP XR	292	881	1	881	27	27	581	1	15	16	164
		May 18, 1998
162	HTEEB42	97922	Uni-ZAP XR	172	1022	20	1022	59	59	461	1	22	23	298
		Mar. 07, 1997
		209070
		May 22, 1997
163	HTEFU65	209324	Uni-ZAP XR	173	1028	1	1028	231	231	462	1	24	25	46
		Oct. 02, 1997
164	HTELP17	203648	Uni-ZAP XR	174	808	1	808	164	164	463	1	20	21	44
		Feb. 09, 1999
165	HTELS08	PTA-1544	Uni-ZAP XR	175	1898	1	1898	15	15	464	1	17	18	158
		Mar. 21, 2000
166	HTLEP53	209641	Uni-ZAP XR	176	818	1	818	73	73	465	1	43	44	101
		Feb. 25, 1998
167	HTPCS72	209423	Uni-ZAP XR	177	3435	2141	3431	2365	2365	466	1	29	30	71
		Oct. 30, 1997
167	HTPCS72	209423	Uni-ZAP XR	293	1598	306	1598	530	530	582	1	29	30	71
		Oct. 30, 1997
168	HTPIH83	PTA-871	Uni-ZAP XR	178	1481	1	1481	118	118	467	1	24	25	230
		Oct. 26, 1999
168	HTPIH83	PTA-871	Uni-ZAP XR	294	530	1	530	111	111	583	1	24	25	140
		Oct. 26, 1999
168	HTPIH83	PTA-871	Uni-ZAP XR	295	1046	359	1046		96	584	1	1	2	86
		Oct. 26, 1999
169	HTSEW17	209138	pBluescript	179	652	1	652	170	170	468	1	34	35	37
		Jul. 03, 1997
170	HTTBI76	209641	Uni-ZAP XR	180	1711	1	1711	133	133	469	1	22	23	133
		Feb. 25, 1998
171	HTTBS64	PTA-841	Uni-ZAP XR	181	2058	1	2058	95	95	470	1	17	18	42
		Oct. 13, 1999
171	HTTBS64	PTA-841	Uni-ZAP XR	296	819	1	819	100	100	585	1	17	18	42
		Oct. 13, 1999
171	HTTBS64	PTA-841	Uni-ZAP XR	297	501	1	501		175	586	1	1	2	76
		Oct. 13, 1999
172	HTXJM03	209580	Uni-ZAP XR	182	2398	211	2398	328	328	471	1	18	19	56
		Jan. 14, 1998
173	HTXON32	203648	Uni-ZAP XR	183	1505	1	1505	72	72	472	1	22	23	52
		Feb. 09, 1999
174	HUFCJ30	209641	pSport1	184	868	1	868	123	123	473	1	29	30	50
		Feb. 25, 1998
175	HUVEB53	209603	Uni-ZAP XR	185	1502	1	1502	14	14	474	1	20	21	45
		Jan. 29, 1998
176	HWAAD63	203570	pCMVSport 3.0	186	3308	1	3308	322	322	475	1	30	31	168
		Jan. 11, 1999
176	HWAAD63	203570	pCMVSport 3.0	298	3306	1	3306	322	322	587	1	30	31	53
		Jan. 11, 1999
176	HWAAD63	203570	pCMVSport 3.0	299	2194	1	2194	312	312	588	1	30	31	169
		Jan. 11, 1999
177	HWADJ89	PTA-1543	pCMVSport 3.0	187	1769	529	1769	581	581	476	1	1	2	43
		Mar. 21, 2000
178	HWBFX31	PTA-1543	pCMVSport 3.0	188	1677	1	1677	271	271	477	1	1	2	52
		Mar. 21, 2000

[0115] Table 1B (Comprised of Tables 1B.1 and 1B.2)

[0116] The first column in Table 1B.1 and Table 1B.2 provides the gene number in the application corresponding to the clone identifier. The second column in Table 1B.1 and Table 1B.2 provides a unique “Clone ID:” for the cDNA clone related to each contig sequence disclosed in Table 1B.1 and Table 1B.2. 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 as determined by directly sequencing the referenced clone. The referenced 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. The third column in Table 1B.1 and Table 1B.2 provides a unique “Contig ID” identification for each contig sequence. The fourth column in Table 1B.1 and Table 1B.2 provides the “SEQ ID NO:” identifier for each of the contig polynucleotide sequences disclosed in Table 1B.

[0117] Table 1B.1

[0118] The fifth column in Table 1B.1, “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 1B.1, 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. The sixth column in Table 1B.1 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. Column 7 in Table 1B.1 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, Wis.). 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 1B. It will be appreciated that depending on the analytical criteria used to predict antigenic determinants, the exact address of the determinant may vary slightly.

[0119] Column 8 in Table 1B.1 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 sequence(s) 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.

[0120] 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 1B 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.

[0121] 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 OMIM™ and National Center for Biotechnology Information, National Library of Medicine (Bethesda, Md.) 2000;. 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 9, Table 1B.1, labelled “OMIM Disease Reference(s). Table 5 is a key to the OMIM reference identification numbers (column 1), and provides a description of the associated disease in Column 2.

[0122] Table 1B.2

[0123] Column 5, in Table 1B.2, provides an expression profile and library code:count for each of the contig sequences (SEQ ID NO:X) disclosed in Table 1B, 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 Table 1B.2, column 5 (preceding the colon), represents the tissue/cell source identifier code corresponding to the code and description provided in Table 4. The second number in column 5 (following the colon) represents the number of times a sequence corresponding to the reference polynucleotide sequence was identified in the corresponding 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 tissue(s) 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.

TABLE 1B.1
					AA
					SEQ			OMIM
Gene	cDNA Clone	Contig	SEQ ID	ORF	ID		Cytologic	Disease
No:	ID	ID:	NO: X	(From-To)	NO: Y	Predicted Epitopes	Band	Reference(s):
1	H2CBU83	884134	11	157-777	300	Pro-62 to Asp-67,	11p14-p13	102772, 106210, 106210, 106210, 106210,
						Arg-74 to Gly-80,		107271, 114550, 115500, 136530, 151390,
						Gln-146 to Glu-168.		179615, 179615, 179616, 180385, 194070,
								194070, 194070, 245349, 602092
	H2CBU83	745366	189	157-312	478
2	H6EDC19	543259	12	389-733	301	Arg-5 to Pro-12.
3	HACBD91	637482	13	117-266	302		3q13.33	600882
4	HAGAQ26	561996	14	251-439	303		7q33	180105, 222800
5	HAGDS35	1352199	15	45-410	304	Leu-31 to Phe-38,
						Glu-47 to Trp-52.
	HAGDS35	543617	190	52-405	479	Leu-31 to Phe-38,
						Glu-47 to Trp-52.
6	HAJAN23	1352364	16	109-1797	305	Pro-186 to Tyr-196,	5q12-q13	126060, 143200, 143200, 181510, 253200,
						Leu-294 to Leu-300,		268800, 268800, 600354, 600354, 600354,
						Ser-380 to Thr-385,		600887
						Thr-486 to Ser-499,
						Phe-513 to Ser-522.
	HAJAN23	872551	191	120-629	480
7	HAJBR69	638516	17	262-423	306
8	HAMFE15	905695	18	1495-2757	307	Leu-8 to Thr-16,	7q34	180105, 222800, 274180
						Gly-93 to Ala-105,
						Arg-136 to Thr-142,
						Lys-195 to Gln-200,
						Lys-241 to His-247,
						Gly-255 to Gln-270,
						Gln-288 to Leu-293,
						Thr-316 to Asp-328,
						Gly-348 to Pro-355,
						Asp-408 to Met-415.
	HAMFE15	823350	192	226-369	481	Ser-39 to Asn-47.
9	HAMGR28	892971	19	98-823	308	Ala-27 to Asp-34,
						Tyr-116 to Leu-125.
	HAMGR28	748223	193	40-651	482	Ala-27 to Asp-34,
						Tyr-116 to Leu-125,
						Arg-185 to Cys-194.
10	HAPOM49	769555	20	251-817	309	Gln-23 to Asp-30,
						Lys-66 to Cys-87.
	HAPOM49	722386	194	448-816	483	Met-1 to Cys-21,
						Cys-41 to Asp-59,
						Pro-104 to His-116.
11	HATBR65	635514	21	252-446	310	Ile-25 to Trp-30.
12	HAUAI83	639009	22	253-399	311	Asn-34 to Lys-42.	19
	HAUAI83	383592	195	575-643	484	Ala-17 to Lys-23.
13	HBAMB15	671835	23	390-569	312		2p16	126600, 126600, 136435, 160980, 600678
14	HBGBA69	1352289	24	124-843	313	Pro-51 to Asp-56,
						Gly-95 to Thr-105,
						Val-132 to Ala-138,
						Pro-229 to Leu-240.
	HBGBA69	709658	196	62-244	485	Thr-52 to Gly-57.
15	HBIAE26	514418	25	75-194	314	Ser-22 to Lys-27.
16	HBINS58	1352386	26	57-578	315	Gly-32 to Gly-37,	1
						Glu-78 to His-87,
						Tyr-102 to Ala-107,
						Pro-115 to Val-122,
						Lys-164 to Tyr-170.
	HBINS58	961712	197	71-592	486	Gly-32 to Gly-37,
						Glu-78 to His-87,
						Tyr-102 to Ala-107,
						Pro-115 to Val-122,
						Lys-164 to Gln-171.
	HBINS58	892924	198	100-732	487	Gly-32 to Gly-37,
						Glu-78 to His-87,
						Tyr-102 to Ala-107,
						Pro-115 to Val-122.
17	HBNAW17	526797	27	77-262	316
18	HCE2F54	634016	28	166-1125	317	His-44 to Pro-50,	16q22.1	103850, 114835, 116800, 140100, 140100,
						Glu-90 to Glu-96,		192090, 192090, 192090, 192090, 245900,
						Gln-111 to Glu-117,		245900, 276600, 600223
						Ser-143 to Gly-151,
						Ala-154 to Leu-166,
						Pro-199 to Ala-216,
						Gly-264 to Asp-272.
19	HCE3G69	728432	29	165-1175	318	Lys-50 to Asp-66,	2q36.1	120070, 120131, 120131, 138030, 259900
						Pro-68 to Glu-77,
						Glu-102 to Glu-107,
						Glu-131 to Leu-146,
						Ala-175 to Glu-183,
						Phe-205 to Lys-216,
						Val-263 to Thr-281,
						Pro-304 to Ala-313.
	HCE3G69	494346	199	165-482	488	Lys-50 to Leu-69.
20	HCE5F43	612796	30	113-931	319	Asn-23 to Ser-32,	10p13	601362
						Trp-61 to Ser-68,
						Ala-130 to Ala-135,
						Thr-141 to Gly-148,
						Asn-176 to Gly-182,
						Pro-197 to Glu-205,
						His-211 to Glu-222,
						Gln-242 to Ile-248,
						Thr-265 to Leu-271.
21	HCEFB80	1143407	31	12-281	320	Met-1 to Ala-8,	22q13.33
						Ser-51 to Leu-62,
						Pro-70 to Lys-78.
	HCEFB80	1046853	200	5-274	489	Met-1 to Ala-8.
22	HCEWE20	543370	32	166-321	321	Ser-17 to Gln-22.
23	HCGMD59	636078	33	438-662	322
24	HCNDR47	1016919	34	21-401	323	Pro-71 to His-92.	1
	HCNDR47	863677	201	124-507	490	Pro-71 to His-92.
	HCNDR47	874128	202	603-632	491	Leu-1 to Thr-9.
25	HCNSM70	637547	35	107-751	324	Met-1 to Ser-6.	11q24	600359, 602574, 602574
	HCNSM70	589445	203	161-436	492	Met-1 to Ser-6.
26	HCUIM65	550208	36	557-700	325
27	HCWDS72	707833	37	19-318	326
28	HCWKC15	553621	38	37-159	327	Lys-28 to Thr-34.
29	HDHEB60	499233	39	568-894	328	Asp-48 to Ser-54.	11p11.2	133701, 168500, 171650, 176930, 176930,
								600623, 600811, 600958
30	HDPBA28	1062783	40	259-3084	329	Gln-33 to Trp-49,	5q14.3
						Gly-161 to Gly-172,
						Ile-207 to Arg-212,
						Asn-414 to Val-419,
						Val-423 to Gln-428,
						Val-436 to Gly-441,
						Lys-467 to Leu-478,
						Phe-497 to Ser-508,
						Met-550 to Gly-560,
						Glu-688 to Thr-697,
						Ile-711 to Gly-720,
						Ala-747 to Gly-759,
						Leu-785 to Phe-791,
						Ser-795 to Gln-800,
						Thr-808 to Lys-813,
						Ser-821 to Phe-832,
						Thr-879 to Glu-889,
						Leu-898 to Gln-904,
						Gln-934 to Met-941.
	HDPBA28	866429	204	69-2894	493	Gln-33 to Trp-49,
						Gly-161 to Gly-172,
						Ile-207 to Arg-212,
						Asn-414 to Val-419,
						Val-423 to Gln-428,
						Val-436 to Gly-441,
						Lys-467 to Leu-478,
						Phe-497 to Ser-508,
						Met-550 to Gly-560,
						Glu-688 to Thr-697,
						Ile-711 to Gly-720,
						Ala-747 to Gly-759,
						Leu-785 to Phe-791,
						Ser-795 to Gln-800.
31	HDPCL63	1019008	41	35-835	330	Ile-4 to Glu-10,
						Gly-58 to Asp-64.
	HDPCL63	847045	205	260-733	494	Lys-72 to Cys-80,
						Leu-90 to Pro-96,
						Ala-110 to Thr-119,
						Glu-121 to Gly-128,
						Ser-140 to Lys-147.
	HDPCL63	897484	206	605-961	495	Pro-8 to Gln-13,
						Thr-38 to Pro-46,
						Pro-100 to Met-108,
						Pro-113 to Pro-118.
32	HDPCO25	460682	42	182-343	331	Pro-22 to His-33,
						Ser-42 to Trp-48.
33	HDPFP29	628254	43	293-451	332
34	HDPGT01	771583	44	8-271	333	Cys-65 to Ser-71.	16q22.1	103850, 114835, 116800, 140100, 140100,
								192090, 192090, 192090, 192090, 245900,
								245900, 276600, 600223
35	HDPHI51	460679	45	245-367	334	Gly-2 to Glu-7,
						Arg-27 to Gly-34.
36	HDPJM30	879325	46	59-1633	335	Arg-15 to Val-22.	21q22.3	120220, 120240, 123580, 151385, 171860,
								190685, 236100, 236200, 240300, 267750,
								600065, 601072, 601145
	HDPJM30	603517	207	259-438	496	Pro-41 to Ala-55.
37	HDPMM88	972734	47	100-2913	336	Met-1 to Ser-13,
						Ser-45 to Phe-51,
						Asn-103 to Lys-113,
						Phe-135 to Gly-140,
						Asp-165 to Pro-178,
						Ser-224 to Ala-229,
						Asn-283 to Arg-288,
						Asp-347 to Tyr-352,
						Thr-367 to Glu-372,
						Gly-420 to Thr-425,
						Glu-456 to Lys-462,
						Phe-466 to Asn-474,
						Glu-480 to Leu-485,
						Asp-673 to Asp-681,
						Gln-684 to Gly-689,
						Leu-841 to Gly-874,
						Gly-890 to Pro-900,
						Ser-902 to Ser-911,
						Leu-918 to Asp-924,
						Ser-930 to Val-935.
	HDPMM88	906121	208	141-467	497	Ser-28 to Phe-34,
						Asn-86 to Tyr-93.
	HDPMM88	902299	209	44-181	498
	HDPMM88	885059	210	419-439	499
	HDPMM88	874074	211	111-146	500
	HDPMM88	854246	212	167-334	501
	HDPMM88	854245	213	28-186	502	Ser-26 to Thr-31.
38	HDPOJ08	731863	48	159-527	337	Lys-30 to Thr-35.	3q25.33	222900
39	HDPPN86	1037893	49	127-267	338
	HDPPN86	895711	214	117-257	503
40	HDPSB18	1043263	50	123-323	339	Lys-23 to Lys-31,	10
						Ala-38 to Ser-43.
	HDPSB18	903816	215	116-307	504
	HDPSB18	905414	216	1525-1566	505
	HDPSB18	732097	217	345-665	506	Lys-57 to Gly-64.
41	HDPSH53	1309174	51	158-430	340	Met-1 to Trp-6,
						Leu-22 to Thr-27,
						Pro-44 to Thr-63.
	HDPSH53	1040056	218	153-536	507	Met-1 to Trp-6,
						Leu-22 to Thr-27,
						Pro-44 to Gly-58,
						Ala-61 to Glu-74,
						Pro-99 to Gly-111,
						Cys-121 to Ser-127.
	HDPSH53	882768	219	212-484	508	Met-1 to Trp-6,
						Leu-22 to Thr-27.
42	HDPSP01	1352280	52	184-2313	341	Gln-75 to Cys-80,
						Glu-97 to Lys-104,
						Glu-114 to Ala-119,
						Thr-177 to Gln-190,
						Asn-230 to Trp-240,
						Glu-269 to Arg-274,
						Pro-279 to Ala-286,
						Pro-323 to Cys-328,
						Asn-362 to Leu-367,
						Thr-390 to Arg-397,
						Leu-490 to Arg-495,
						Gln-556 to Leu-561,
						Gln-657 to Val-674.
	HDPSP01	689129	220	227-1153	509	Gln-75 to Cys-80.
43	HDPSP54	744440	53	2356-2499	342	Pro-29 to Lys-37.	1q21.2	104770, 107670, 110700, 145001, 146760,
								146790, 191315, 601412, 601652, 601863,
								602491
	HDPSP54	502472	221	179-343	510
44	HDPUW68	812737	54	40-1440	343	Gly-12 to Tyr-26,
						Val-52 to Asp-59,
						Gln-88 to Asp-93,
						Arg-124 to Asn-129,
						His-193 to Arg-198,
						Gln-207 to Thr-213,
						Gln-338 to Arg-346,
						Ser-378 to Ala-384,
						Ser-413 to Arg-420,
						Ser-428 to Glu-434,
						His-443 to Ser451,
						Glu-454 to Ser-461.
45	HDPXY01	879048	55	23-319	344	Pro-39 to Trp-44.	17
	HDPXY01	904768	222	33-329	511	Pro-39 to Trp-44.
	HDPXY01	895716	223	539-607	512
	HDPXY01	895715	224	1190-1267	513
46	HDTBD53	972757	56	288-1385	345	Glu-91 to Arg-117,	3p25.1	193300, 193300, 227646
						Lys-124 to Ser-136,
						Tyr-191 to Glu-200,
						Glu-265 to Lys-272.
	HDTBD53	906342	225	292-1389	514	Glu-91 to Arg-117,
						Lys-124 to Ser-136.
47	HDTBV77	785879	57	326-2149	346	Lys-5 to Lys-10,	10p15.1
						Asn-33 to Lys-39,
						Asp-48 to Lys-54,
						Pro-62 to Asp-67,
						Asn-116 to Arg-123,
						His-157 to Ala-162,
						Val-242 to Lys-249,
						Val-251 to Asp-264.
48	HDTDQ23	1306984	58	132-302	347	Arg-24 to Arg-31,
						Ile-33 to Trp-41,
						Met-43 to His-52.
	HDTDQ23	879009	226	148-471	515	Arg-24 to Arg-31,
						Ile-33 to Gly-41.
	HDTDQ23	751707	227	148-369	516	Arg-24 to Arg-31.
49	HE2DE47	619852	59	808-2427	348	Leu-9 to Tyr-15,
						Asp-34 to Gln-46,
						Pro-51 to Asp-57,
						Gly-88 to Thr-104,
						Thr-123 to Ser-128.
	HE2DE47	382025	228	515-757	517	Leu-31 to Asn-38.
50	HE2NV57	740750	60	99-398	349	Ala-84 to Gln-93.
51	HE2PH36	570903	61	28-228	350
52	HE8DS15	847060	62	91-309	351		18
53	HE9HY07	420063	63	35-160	352	Pro-35 to Phe-41.
54	HEOMQ63	603533	64	123-266	353		20p12.1
55	HEPAB80	1307790	65	73-438	354	Met-1 to Pro-6,
						Glu-58 to Cys-63,
						Glu-65 to Gly-72,
						Thr-74 to Asn-88,
						Tyr-104 to Trp-109.
	HEPAB80	570048	229	67-435	518	Met-1 to Pro-6,
						Glu-58 to Cys-63,
						Glu-65 to Gly-72,
						Thr-74 to Val-87.
56	HFABH95	566712	66	199-549	355
57	HFAEF57	534142	67	232-492	356	Leu-69 to Leu-74.
58	HFCEB37	411345	68	487-519	357
59	HFFAD59	520369	69	44-181	358	Lys-13 to Asn-19,	4q32-q34	189800, 208400, 231675
						Asn-27 to Asn-35.
60	HFGAD82	513669	70	1019-1135	359		Xp22.2	300075, 300077, 301200, 302350, 302801,
								305435, 306000, 306000, 307800, 308800,
								309510, 311200, 312040, 312170, 312700,
								313400
61	HFIUR10	532060	71	50-184	360	Gln-31 to Pro-39.
62	HFTBM50	545012	72	158-262	361	Ala-19 to Lys-34.	4q12	103600, 103600, 103600, 104150, 104150,
								104500, 164920, 164920, 164920, 170650,
								600900
63	HFTDZ36	545726	73	547-753	362		16q24.3	155555, 155555, 227650, 253000, 602783
64	HFXBL33	778070	74	152-640	363
65	HFXJX44	701988	75	98-241	364
66	HFXKT05	658690	76	204-443	365	Leu-16 to Ser-23,	1p34.1	120550, 120570, 120575, 121800, 130500,
						Ser-38 to Pro-43,		133200, 138140, 171760, 171760, 178300,
						Gly-53 to Leu-60.		255800
67	HGBHI35	570262	77	87-965	366	Pro-10 to Arg-15,	1p32.2	120260, 138140, 178300
						Leu-96 to Ser-103,
						Gly-172 to Pro-178,
						Gln-213 to Asp-218,
						Asn-268 to Leu-275,
						Arg-282 to Phe-289.
68	HGLAF75	566838	78	231-596	367	Ser-40 to Gly-45,
						Leu-73 to Arg-80.
69	HHENV10	562772	79	143-295	368	Asp-26 to Leu-36,
						Leu-42 to Phe-50.
70	HHGCG53	340818	80	230-361	369		8
71	HHGCM76	662329	81	270-536	370		17
	HHGCM76	383547	230	270-302	519
72	HHPEN62	695134	82	183-1709	371	Met-98 to Gln-107,
						Gly-120 to Gly-126,
						Pro-138 to Trp-145,
						Leu-159 to Gly-169,
						Val-211 to Arg-217,
						Cys-256 to His-262,
						Glu-320 to Val-327,
						Phe-399 to Asn-406,
						Asp-444 to Ser-450,
						Asp-475 to Trp-488.
73	HJABB94	456466	83	74-307	372	Ala-28 to His-41,	13q14.12	180200, 180200, 180200, 180200, 600631
						Pro-43 to Gln-64.
74	HJACG30	895505	84	291-425	373	Thr-26 to Asn-39.	15, X
	HJACG30	821341	231	50-439	520	Pro-57 to Pro-64.
	HJACG30	774300	232	350-715	521	Lys-1 to Gly-8.
75	HJBCY35	719729	85	232-1215	374	Glu-35 to His-41,	7p22.3
						Ser-62 to Ala-67,
						Pro-145 to Leu-155,
						Glu-157 to Ser-163,
						Arg-190 to Val-197,
						Asp-208 to Pro-215,
						Ser-247 to Pro-252.
76	HJPAD75	651337	86	60-335	375	Pro-42 to Cys-50,
						Leu-61 to Ala-66.
77	HKABZ65	862030	87	77-808	376	Ser-25 to Ala-31,
						Gln-146 to Ser-151,
						His-231 to Asn-236.
	HKABZ65	665424	233	69-800	522	Ser-25 to Ala-31,
						Gln-146 to Ser-151,
						His-231 to Asn-236.
78	HKACB56	554616	88	27-269	377	Tyr-39 to Lys-58.
79	HKACD58	1352202	89	38-940	378	Thr-42 to Pro-53,
						Val-78 to Glu-86,
						Glu-103 to Met-112,
						Ala-124 to Gly-131,
						Trp-158 to Glu-168,
						Gln-189 to Phe-210,
						Ala-221 to Gly-226,
						Arg-274 to Asp-284,
						Ala-294 to Gly-299.
	HKACD58	552465	234	35-499	523	Thr-42 to Pro-53,
						Val-78 to Glu-86,
						Glu-103 to Met-112,
						Ala-124 to Gly-131.
80	HKAEV06	1352263	90	501-1814	379	Thr-6 to Trp-13,
						Thr-75 to Gln-80,
						Thr-112 to Tyr-117,
						Leu-133 to Pro-138,
						Ala-146 to Phe-153,
						Gln-319 to Ser-325,
						Val-354 to His-372,
						Pro-391 to Gly-396,
						Val-405 to Thr-412,
						Ile-425 to Asp-437.
	HKAEV06	638238	235	197-370	524	Thr-6 to Trp-13.
81	HKAFT66	946512	91	508-831	380	Ser-51 to Thr-57.
	HKAFT66	889258	236	508-831	525	Ser-51 to Thr-57.
	HKAFT66	904790	237	234-347	526	Gln-23 to Asp-28.
82	HKB1E57	876571	92	178-879	381	Ser-7 to Pro-14,
						Arg-47 to Arg-52,
						His-117 to Val-123,
						Glu-142 to Thr-149,
						Leu-162 to Ala-167,
						Gly-172 to Asn-177,
						Thr-226 to Ala-232.
	HKB1E57	654871	238	30-170	527	Met-1 to Tyr-6,
						Thr-38 to Ala-44.
83	HKFBC53	1352286	93	64-1473	382	Arg-52 to Ala-58,
						Thr-121 to Lys-126,
						Gly-156 to Gln-164,
						Gly-201 to Glu-215,
						Thr-432 to Gly-450,
						Glu-461 to Gly-466.
	HKFBC53	701893	239	41-1369	528	Ala-28 to Ala-33,
						Arg-38 to Leu-48,
						Thr-120 to Lys-125,
						Gly-155 to Gln-163,
						Gly-200 to Glu-214.
	HKFBC53	513190	240	3-929	529	Ala-1 to Gly-6,
						Ala-10 to Tyr-18.
	HKFBC53	383426	241	3-731	530	Ala-1 to Gly-6,
						Ala-10 to Tyr-18.
84	HKGDL36	877489	94	53-835	383	Pro-36 to Gly-42,	Xp11.23	300047, 300071, 300110, 300600, 301000,
						Gly-54 to Arg-65,		301000, 301830, 309470, 309500, 309610,
						Ala-85 to Ala-91,		309850, 311050, 312060
						Ala-95 to Gln-102,
						Ala-115 to Pro-121,
						Pro-166 to Asp-191,
						Lys-243 to Ala-249.
	HKGDL36	704088	242	55-501	531	Pro-36 to Gly-42,
						Pro-64 to Ala-76,
						Gly-83 to Ala-90,
						Ser-100 to Cys-108,
						Thr-126 to Ser-135.
85	HKISB57	625956	95	130-417	384	Ala-23 to Arg-36,	22q12.2	101000, 101000, 101000, 101000, 123620,
						His-38 to Ala-46,		138981, 188826, 600850, 601669
						Pro-50 to Gly-56,
						Arg-85 to Val-94.
86	HKMLM11	514788	96	82-474	385	Ala-59 to Thr-68,
						Glu-72 to Ser-108,
						Glu-115 to Lys-126.
87	HKMMW74	581399	97	202-327	386
88	HLDON23	636083	98	368-709	387	Arg-28 to Gln-36.	15q23	118485, 151670, 231680, 272800, 272800,
								272800, 276700, 600374, 601780
89	HLDQR62	753742	99	520-1005	388	Arg-122 to Ser-139,	5p15.2-	123000, 602568
						Met-144 to Glu-149.	p14.1
90	HLDQU79	740755	100	99-1142	389	Leu-68 to Lys-74,	10q21-q22	126090, 129010, 142600, 154545, 250850,
						Tyr-109 to Lys-115,		601386, 601493
						Gln-200 to Val-205,
						Lys-207 to Lys-214,
						Glu-237 to Ile-244,
						Ala-271 to Thr-279,
						Ser-317 to Ser-329,
						Gln-342 to Gly-348.
91	HLHAL68	684216	101	30-164	390	Leu-32 to His-38.
92	HLIBD68	778073	102	186-338	391	Met-37 to Ser-43.
93	HLICQ90	791828	103	249-869	392	Pro-55 to Gly-66,
						Phe-92 to Leu-103.
94	HLTHR66	699812	104	5-232	393
95	HLTIP94	1087335	105	226-516	394	Gly-4 to Glu-9,	17
						Asp-22 to Cys-28,
						Glu-39 to Leu-44,
						Phe-88 to Phe-94.
	HLTIP94	1035443	243	226-423	532	Gly-4 to Glu-9.
	HLTIP94	1047690	244	3-899	533	Gly-1 to Glu-8,
						Gly-37 to Gly-61,
						Gln-71 to Phe-81,
						Asp-95 to Gly-103,
						Leu-126 to Ile-131,
						Val-166 to Glu-171.
96	HLWAA17	629552	106	436-996	395	Lys-17 to Glu-27,	1q21	104770, 107670, 110700, 135940, 145001,
						Gln-40 to Gly-47.		146790, 152445, 152445, 159001, 174000,
								179755, 182860, 182860, 182860, 191315,
								230800, 230800, 266200, 600897, 601105,
								601412, 601652, 602491
97	HLYAC95	778075	107	92-232	396
98	HMADK33	561941	108	161-619	397	Gly-43 to Gly-55.	16p13	138760, 186580, 249100, 266600, 600760,
								600760, 600761, 600761
99	HMAMI15	1352406	109	4-1023	398	Gly-33 to Lys-41,
						Pro-52 to Lys-60,
						Asn-81 to Ala-86,
						Lys-156 to Met-164,
						Gln-283 to Lys-292,
						Glu-303 to Gly-308.
	HMAMI15	1049263	245	3-923	534	Gly-33 to Lys-41,
						Pro-52 to Lys-60,
						Asn-81 to Ala-86.
100	HMCFY13	635301	110	175-369	399
101	HMDAB56	560676	111	273-407	400
102	HMEED18	560775	112	34-699	401	Gln-85 to Lys-91,
						Pro-106 to Ser-117,
						Pro-124 to Ala-130,
						Trp-154 to Trp-160.
103	HMEFT54	520307	113	332-451	402
104	HMEGF92	520304	114	92-280	403	Ser-34 to Ser-39.
105	HMSDL37	973996	115	531-725	404	Ser-31 to Lys-45,	3, 3p
						Pro-47 to Pro-53,
						Ser-58 to Arg-63.
	HMSDL37	895429	246	528-722	535	Ser-31 to Lys-45,
						Pro-47 to Pro-53,
						Ser-58 to Arg-63.
	HMSDL37	904241	247	565-645	536
	HMSDL37	750927	248	2-151	537
106	HMSFI26	560229	116	120-308	405
107	HMVBS81	639203	117	34-453	406		11q13	102200, 106100, 131100, 131100, 131100,
								133780, 147050, 153700, 161015, 164009,
								168461, 168461, 168461, 180721, 180840,
								191181, 193235, 209901, 232600, 259700,
								259770, 600045, 600319, 600528, 601884
108	HMWDC28	460487	118	124-252	407
109	HMWFT65	562063	119	72-437	408
110	HNEEE24	553558	120	213-428	409
111	HNFFC43	753337	121	488-691	410	Asp-21 to Ser-29.	12q13.12	120140, 120140, 120140, 120140, 120140,
								120140, 120140, 126337, 600808, 601284,
								601769, 601769, 602116
112	HNFIY77	634551	122	228-929	411	Pro-47 to Met-53,
						Ser-130 to Ser-138.
113	HNFJF07	577013	123	86-286	412	Val-25 to Gly-33.
114	HNGFR31	553552	124	108-380	413
115	HNGIJ31	519120	125	135-245	414	Pro-18 to Glu-25.
116	HNGJE50	561568	126	77-217	415
117	HNGND37	839224	127	388-636	416	Asn-46 to Ser-54.
118	HNGOI12	1041375	128	27-200	417	Met-1 to Gly-9.	11
	HNGOI12	838184	249	27-200	538	Met-1 to Gly-9.
	HNGOI12	839283	250	596-877	539
119	HNHEU93	634851	129	57-302	418
120	HNHFM14	664507	130	38-280	419	Glu-67 to Ala-74.	1
121	HNHNB29	895462	131	40-201	420	Glu-17 to Lys-30,
						Val-43 to Asn-53.
122	HNHOD46	843488	132	12-251	421
123	HNTBI26	1310821	133	28-990	422	Pro-56 to Pro-63,
						Met-92 to Thr-98,
						Ser-112 to Pro-120,
						Pro-162 to Glu-173,
						Ala-200 to Ser-210,
						Lys-311 to Asn-320.
	HNTBI26	796807	251	32-547	540	Pro-56 to Pro-63,
						Met-92 to Thr-98,
						Ser-112 to Pro-120,
						Pro-162 to Ser-169.
	HNTBI26	590738	252	16-411	541	Pro-56 to Pro-63,
						Met-92 to Thr-98,
						Arg-107 to Pro-120.
124	HNTBL27	545534	134	100-447	423	Arg-45 to Thr-52,	3p21.31	116806, 168468, 182280, 212138, 600163
						Tyr-60 to Gly-66,
						Ala-87 to Trp-92,
						Leu-105 to Ser-115.
125	HNTCE26	1160395	135	111-1316	424	Tyr-2 to Gly-15,
						Trp-192 to Asp-199,
						Lys-248 to Leu-253,
						Arg-330 to Lys-336,
						Gln-354 to Val-364,
						Val-383 to Ser-392.
	HNTCE26	853373	253	57-422	542	Arg-75 to Lys-81,
						Gln-99 to Asp-109.
126	HNTNI01	1352285	136	307-534	425	Lys-71 to Trp-76.
	HNTNI01	699848	254	306-455	543
127	HODDF13	684307	137	46-171	426	Thr-28 to Ser-40.
128	HODDN92	422913	138	434-541	427
129	HOFMQ33	1184465	139	49-1503	428	Leu-37 to Gly-44,
						Thr-137 to Leu-144,
						Ala-178 to Asn-184,
						Asp-194 to Val-201,
						Leu-252 to Glu-258,
						Asp-280 to Tyr-293,
						Asn-296 to Thr-301,
						Asp-322 to Asp-348,
						Asn-363 to Ser-368,
						His-370 to Thr-378,
						Asn-380 to Cys-386,
						Glu-391 to Cys-399,
						Leu-421 to Arg-426,
						Glu-454 to Tyr-459.
	HOFMQ33	919896	255	48-1502	544	Leu-37 to Gly-44,
						Pro-46 to Gly-51,
						Thr-137 to Leu-144,
						Ala-178 to Asn-184,
						Asp-194 to Val-201,
						Leu-252 to Glu-258,
						Asp-280 to Tyr-293,
						Asn-296 to Thr-301,
						Asp-322 to Asp-348,
						Asn-363 to Ser-368,
						His-370 to Thr-378,
						Asn-380 to Cys-386,
						Glu-391 to Cys-399,
						Leu-421 to Arg-426,
						Glu-454 to Tyr-459.
	HOFMQ33	906694	256	78-875	545	Leu-37 to Gly-43.
	HOFMQ33	902639	257	724-741	546
	HOFMQ33	702186	258	123-374	547	Met-2 to Ser-9.
130	HOFOC73	931871	140	18-407	429	Pro-22 to Cys-30,
						Gly-43 to Tyr-53,
						Ser-55 to Trp-65,
						Ala-76 to His-81,
						Pro-101 to Gly-108,
						Pro-121 to Gly-127.
	HOFOC73	907073	259	23-226	548	Thr-47 to Pro-55.
	HOFOC73	907072	260	127-171	549	Pro-1 to Val-7.
	HOFOC73	878863	261	142-162	550
131	HOQBJ82	1352356	141	361-852	430	Ser-30 to Met-36,
						Ile-38 to Pro-46,
						Gln-78 to Gly-88,
						Thr-98 to Pro-105,
						Gly-110 to Ser-122,
						Ser-136 to Trp-144.
	HOQBJ82	858338	262	102-584	551	Ser-30 to Met-36,
						Ile-38 to Pro-46,
						Gln-78 to Gly-88,
						Thr-98 to Pro-105,
						Gly-110 to Ser-122.
	HOQBJ82	857453	263	55-1029	552
132	HOSBY40	589431	142	89-259	431
133	HOSDJ25	854234	143	1076-1195	432	Gly-18 to Lys-23,
						Pro-31 to Gly-38.
	HOSDJ25	566845	264	146-268	553	Gly-18 to Lys-23,
						Pro-31 to Gly-38.
134	HPEAD79	520202	144	51-176	433	Lys-16 to Ser-21,
						Gly-36 to Asp-41.
135	HPIBO15	1310868	145	128-763	434	Asp-40 to Glu-50,
						Ser-59 to Gly-69,
						Leu-109 to Lys-117,
						Tyr-130 to Leu-137,
						Leu-140 to Glu-160,
						Gly-202 to Tyr-208.
	HPIBO15	590741	265	127-648	554	Asp-40 to Glu-50,
						Ser-59 to Gly-69,
						Ala-98 to His-105,
						Arg-108 to Glu-114,
						Pro-124 to Ser-138,
						Ala-143 to Gly-154.
136	HPJBI33	685699	146	236-397	435	Arg-30 to Gln-36.
137	HPJBK12	1011467	147	126-272	436		4,8
	HPJBK12	525375	266	119-265	555
	HPJBK12	796925	267	969-1001	556
	HPJBK12	699587	268	509-523	557
138	HPMDK28	846357	148	64-669	437	Ala-55 to Asn-60,	1p36.33
						Lys-65 to Met-71,
						Leu-75 to Asn-86,
						Asp-93 to Asp-110,
						Leu-130 to Cys-138,
						Gln-149 to Glu-154,
						Thr-172 to Ile-179,
						Glu-185 to Arg-192.
	HPMDK28	639118	269	58-663	558	Ala-55 to Asn-60,
						Lys-65 to Met-71,
						Leu-75 to Asn-86,
						Asp-93 to Asp-110,
						Leu-130 to Cys-138,
						Gln-149 to Glu-154,
						Thr-172 to Ile-179,
						Glu-185 to Arg-192.
139	HPRAL78	1352342	149	62-1321	438	Pro-31 to Thr-48,	3p25.2	193300, 193300, 227646
						Arg-62 to Gly-70,
						Ala-74 to Glu-87,
						Lys-123 to Asp-129,
						Pro-162 to Gly-167,
						Glu-170 to Gly-189,
						Arg-220 to Asn-228,
						Glu-248 to Ala-258,
						Gly-285 to Gly-300,
						Pro-315 to Gly-327,
						Ser-406 to Arg-411.
	HPRAL78	844216	270	70-1245	559	Pro-31 to Thr-48,
						Arg-62 to Gly-70,
						Ala-74 to Glu-87,
						Lys-123 to Asp-129,
						Pro-162 to Gly-167,
						Glu-170 to Gly-189,
						Arg-220 to Asn-228.
	HPRAL78	484735	271	148-339	560	Ser-49 to Arg-54.
140	HRABA80	882176	150	144-452	439	Ala-30 to Gly-36,
						Asp-45 to Trp-50,
						Lys-65 to Cys-71,
						Pro-80 to Cys-87.
	HRABA80	588460	272	130-438	561	Ala-30 to Gly-36,
						Asp-45 to Trp-50,
						Lys-65 to Cys-71,
						Pro-80 to Cys-87.
141	HRACD15	871221	151	252-410	440
	HRACD15	706332	273	252-413	562
142	HRACJ35	877666	152	132-1550	441	Arg-31 to Lys-37,	8q22.2	148900, 216550
						Lys-58 to Glu-65,
						Asp-157 to Gly-168,
						Ile-219 to Gly-225,
						Ala-260 to Ser-268,
						Thr-276 to Glu-282.
	HRACJ35	730504	274	99-1517	563	Arg-31 to Lys-37,
						Lys-58 to Glu-65,
						Asp-157 to Gly-168,
						Ile-219 to Gly-225,
						Ala-260 to Ser-268,
						Thr-276 to Glu-282.
	HRACJ35	470546	275	1-534	564	Ile-9 to Gly-15,
						Ala-50 to Ser-58,
						Thr-66 to Glu-72.
143	HRGBL78	910133	153	30-1109	442	Thr-48 to Arg-56,	1
						Pro-122 to Glu-127,
						Lys-135 to Cys-143,
						Ala-180 to Gly-185,
						Ala-230 to Tyr-238,
						Thr-244 to Gln-255,
						Pro-274 to Ser-279,
						Thr-284 to Phe-306,
						Leu-345 to Thr-354.
	HRGBL78	904040	276	30-626	565	Thr-48 to Arg-56,
						Pro-122 to Glu-127,
						Ala-136 to Tyr-141.
	HRGBL78	904621	277	11-19	566
	HRGBL78	863802	278	1048-1146	567	Pro-24 to Arg-32.
144	HROAJ39	1181699	154	10-1146	443	Ile-4 to Tyr-10,	18q21.32	174810, 601567, 602080
						Arg-119 to Pro-126,
						Glu-152 to Gly-158,
						Thr-209 to Phe-215.
	HROAJ39	1114849	279	31-879	568	Arg-40 to Pro-47,
						Glu-73 to Gly-79,
						Thr-130 to Phe-136,
						Lys-277 to Lys-283.
	HROAJ39	1027712	280	247-1104	569	Arg-40 to Pro-47,
						Glu-73 to Gly-79,
						Thr-130 to Phe-136.
145	HROBD68	827306	155	122-268	444	Thr-19 to Thr-25.
146	HSAWD74	460527	156	142-570	445	Leu-51 to Gly-77,	7
						Ile-117 to Pro-125.
	HSAWD74	371416	281	122-256	570	Thr-25 to Cys-30,
						Pro-35 to Arg-42.
147	HSDEK49	1352253	157	60-1256	446	Val-29 to Val-37,	Xq12-q13.3	300011, 300011, 300011, 300127, 305450,
						Asp-71 to His-76,		309605, 313700, 313700, 313700, 313700,
						Gln-78 to Gly-84,		313700, 314580
						Met-105 to His-110,
						Trp-117 to Asn-123,
						Lys-179 to Pro-187,
						Gly-218 to Asp-224,
						Leu-237 to Ala-243,
						Thr-256 to Asp-268,
						Ser-275 to Lys-280,
						Arg-308 to Glu-314,
						Glu-326 to Glu-332,
						Cys-343 to Asp-359.
	HSDEK49	625998	282	126-1043	571	Val-29 to Val-37,
						Asp-71 to His-76,
						Gln-78 to Gly-84,
						Met-105 to His-110,
						Trp-117 to Gly-122,
						Gln-136 to Lys-141,
						Leu-143 to Ala-149,
						Thr-162 to Asp-174,
						Ser-181 to Lys-186,
						Arg-214 to Glu-220,
						Glu-232 to Glu-238,
						Cys-249 to Asp-265.
148	HSDFJ26	834619	158	99-767	447	Ala-21 to Glu-31,
						Thr-37 to Cys-43,
						Asp-62 to Ser-79,
						Lys-134 to Gly-146,
						Leu-164 to Met-169,
						Glu-171 to Lys-201.
	HSDFJ26	836071	283	99-317	572	Ala-21 to Glu-31,
						Thr-37 to Cys-43,
						Pro-64 to Asp-69.
149	HSDSB09	1301498	159	16-423	448	Glu-33 to Glu-56,
						Thr-75 to Cys-81.
	HSDSB09	463645	284	22-387	573	Glu-33 to Glu-56,
						Thr-75 to Cys-81.
150	HSDSE75	545057	160	160-705	449	Tyr-15 to Leu-59,
						Ala-68 to Asp-85,
						Pro-87 to Asn-96,
						His-120 to Lys-129,
						Ser-153 to Gln-170.
151	HSIDJ81	589447	161	8-184	450	Glu-37 to Gly-45.
152	HSKDA27	1352409	162	786-3635	451	Gly-31 to Arg-36,
						Thr-55 to Glu-62,
						Ser-64 to Ser-79,
						Arg-87 to Asp-96,
						Arg-103 to Ala-109,
						Asp-120 to Arg-126,
						Gly-294 to Gly-302,
						Ser-305 to Ala-318,
						Val-320 to Arg-327,
						Pro-344 to Thr-351,
						Thr-383 to Thr-399,
						Leu-414 to Lys-435,
						Thr-449 to Ala-457,
						Gly-461 to Asn-479,
						Gly-483 to Gln-498,
						Ser-503 to Arg-514,
						Lys-532 to Ala-559,
						Leu-563 to Ser-611,
						Lys-632 to Tyr-638,
						Asn-667 to Lys-672,
						Leu-701 to Met-707,
						Ser-745 to Lys-755,
						Lys-761 to Leu-768,
						Pro-787 to Trp-792,
						Lys-871 to Met-883,
						Pro-914 to Tyr-923,
						Ser-925 to Arg-939,
						Glu-942 to Tyr-950.
	HSKDA27	1074734	285	127-1653	574	Gly-31 to Arg-36,
						Thr-55 to Glu-62,
						Ser-64 to Ser-79,
						Arg-87 to Asp-96,
						Arg-103 to Ala-109,
						Asp-120 to Arg-126,
						Gly-294 to Gly-302,
						Ser-305 to Ala-318,
						Val-320 to Arg-327,
						Pro-342 to Thr-351,
						Thr-383 to Thr-399,
						Leu-414 to Lys-435,
						Thr-449 to Ala-457,
						Gly-461 to Asn-479,
						Gly-483 to Gln-498,
						Asn-504 to Val-509.
	HSKDA27	872570	286	12-1673	575	Gly-27 to Arg-32,
						Thr-51 to Glu-58,
						Ser-60 to Ser-75,
						Arg-83 to Asp-92,
						Arg-99 to Ala-105,
						Asp-116 to Arg-122,
						Gly-290 to Ala-314,
						Val-316 to Arg-323,
						Pro-338 to Arg-345,
						Thr-358 to His-375,
						Arg-403 to Ser-408,
						Ser-420 to Ser-436,
						Thr-447 to Ala-455,
						Gly-459 to Asn-477,
						Gly-481 to Gln-496,
						Ser-501 to Arg-512,
						Lys-530 to Lys-554.
153	HSKGN81	676075	163	353-1132	452	Ile-60 to Asn-69,	22q13.2	188826
						Leu-106 to Asp-112,
						Glu-130 to Gly-136,
						Phe-160 to Glu-167,
						Pro-184 to Cys-190,
						Glu-197 to Ser-202,
						Arg-215 to Glu-221,
						Thr-237 to Pro-242.
	HSKGN81	409905	287	537-608	576	Thr-11 to Pro-22.
154	HSNAD72	467397	164	220-327	453
155	HSNMC45	1352201	165	225-389	454	Glu-23 to Asn-31,
						Thr-38 to Gly-48.
	HSNMC45	545060	288	232-309	577
156	HSQFP66	460537	166	96-332	455	Ser-6 to Arg-15.
157	HSRFZ57	892171	167	82-207	456
158	HSUBW09	413246	168	153-323	457	Asp-23 to Gly-29.
159	HSVBU91	596868	169	256-528	458	Asp-26 to Asn-31,	7q11.23	116860, 129900, 233700, 600079
						Ser-37 to His-49,
						Ala-65 to Ser-73.
160	HTAEE28	1018291	170	319-1167	459	Pro-255 to Leu-264.
	HTAEE28	882919	289	372-737	578
	HTAEE28	864120	290	124-771	579
161	HTECC05	1352365	171	13-546	460	Gly-41 to Leu-46,
						Asp-67 to Thr-75,
						Ile-114 to Gly-122,
						Pro-156 to Trp-161.
	HTECC05	877448	291	21-404	580	Gly-41 to Leu-46,
						Asp-67 to Thr-75,
						Ile-114 to Pro-127.
	HTECC05	666743	292	27-518	581	Gly-41 to Leu-46,
						Asp-67 to Thr-75,
						Ile-114 to Ala-123.
162	HTEEB42	206980	172	59-952	461	Met-1 to His-7.	21q21.2
163	HTEFU65	543396	173	231-371	462	Gly-35 to Gly-40.
164	HTELP17	836072	174	164-298	463		3p12-p11.1	164500, 176880, 232500, 600151, 600795
165	HTELS08	847090	175	15-491	464	Pro-98 to Gln-106.
166	HTLEP53	634852	176	73-378	465	Ser-33 to Lys-43.
167	HTPCS72	854941	177	2365-2577	466		1q23.1	107300, 131210, 136132, 145001, 173610,
								601652
	HTPCS72	566683	293	530-745	582
168	HTPIH83	919916	178	118-810	467	Ser-29 to Ser-34,	Xq22.3-23	300046, 300067, 300067, 300121, 300121,
						Ser-186 to Asp-196,		301201, 301835, 311850
						Arg-206 to Ser-225.
	HTPIH83	895024	294	111-530	583	Ser-29 to Ser-34.
	HTPIH83	898088	295	96-353	584
169	HTSEW17	460579	179	170-283	468
170	HTTBI76	637725	180	133-534	469	Glu-55 to Arg-61,
						Gln-84 to Ser-92,
						Ser-99 to Ser-104.
171	HTTBS64	1008159	181	95-223	470	Leu-37 to Asn-42.
	HTTBS64	863187	296	100-228	585	Leu-37 to Asn-42.
	HTTBS64	754125	297	175-402	586	Lys-41 to Arg-46.
172	HTXJM03	603918	182	328-498	471	Asp-51 to His-56.
173	HTXON32	838288	183	72-230	472	Ala-45 to Gly-50.
174	HUFCJ30	638402	184	123-275	473	Pro-31 to Ala-37.
175	HUVEB53	571200	185	14-151	474		20p12	112261, 176640, 176640, 176640, 236700,
								601920
176	HWAAD63	838626	186	322-825	475	Pro-53 to Trp-61.
	HWAAD63	833089	298	322-483	587
	HWAAD63	793875	299	312-818	588
177	HWADJ89	799506	187	581-709	476		1p36.31-	120550, 120570, 120575, 130500, 133200,
							p36.11	600975
178	HWBFX31	799427	188	271-426	477