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A 4.1 kb genomic region, spanning the insulin (INS) gene, confers genetic susceptibility to Type 1 or insulin-dependent diabetes mellitus (IDDM). Ten polymorphisms within this region form two predominant, complementary haplotypes. We have been studying the effects of these polymorphisms on the levels of insulin mRNA. Cloned genomic DNA fragments representing these two separate haplotypes were transiently transfected into a rodent pancreatic beta cell line, HIT-T15. These studies revealed that insulin mRNA levels were consistently higher in the transfectants expressing the diabetic haplotype. Over-expression of insulin mRNA may provide the basic mechanism for the diabetic susceptibility encoded at the INS locus.

Original publication

DOI

10.1093/hmg/4.4.501

Type

Journal article

Journal

Hum Mol Genet

Publication Date

04/1995

Volume

4

Pages

501 - 506

Keywords

Animals, Base Sequence, Chromosome Mapping, Cloning, Molecular, DNA Primers, Diabetes Mellitus, Type 1, Gene Expression Regulation, Guinea Pigs, Haplotypes, Humans, Insulin, Molecular Sequence Data, RNA, Messenger, Transfection, Tumor Cells, Cultured