LARGE-SCALE COLLECTION OF PANCREATIC ISLET ESTS AND CHROMOSOMAL MAPPING

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Diabetes mellitus is characterized by elevated plasma glucose levels due to an absolute or relative deficiency of insulin. The genetic linkage studies looking for diabetes susceptibility genes are well underway in many labs, but this "positional cloning" is still a laborious work. Because of the central role of the pancreatic islets in the regulation of glucose homeostasis, we focused on this tissue as a primary site of expression of the major diabetogenic genes and created a database of genes expressed in this tissue as expressed sequence tags (ESTs). The analysis of 6,055 ESTs by database searches idicated that approximately 50% of the cDNAs so far isolated represented unknown human genes. Of these, 2,731 and 402 ESTs shoewed exact match with and significant similarty to known genes, respectively. 2,390 ESTs showed homology with other ESTs. 408 ESTs had no database match. Approximately half of these genes have been assigned to the chromosome by dbSTS search, RH mapping and/or FISH.The characterization of the tissue distribution and chromosomal localization of novel ESTs will facilitate the "positional candidate" approach. The pancreatic islet ESTs obtained in this project will provide a unique key source of new candidate genes for genetic studies of diabetes.