HUMAN GLUCAGON-LIKE PEPTIDE-1 RECEPTOR GENE - LOCALIZATION TO CHROMOSOME BAND-6P21 BY FLUORESCENCE IN-SITU HYBRIDIZATION AND LINKAGE OF A HIGHLY POLYMORPHIC SIMPLE TANDEM REPEAT DNA POLYMORPHISM TO OTHER MARKERS ON CHROMOSOME-6

Glucagon-like peptide-1 is a fragment of proglucagon secreted by intes tinal L-cells. It has potent glucose-dependent insulin secretory effec ts and also suppresses gastric acid secretion in the stomach. The biol ogical actions of GLP-1 are mediated by the GLP-1 receptor, the struct ure of which has recently been determined. Defects in insulin secretio n are a common feature of NIDDM and as such the GLP-1 receptor is a ca ndidate for contributing to the development of this clinically and gen etically heterogeneous disorder. As a first step in determining the ro le of the GLP-1 receptor in the development of NIDDM, we have isolated the human GLP-1 receptor gene and mapped it to chromosome 6, band p21 .1, using the technique of fluorescence in situ hybridization. We also identified a simple tandem repeat DNA polymorphism in the human GLP-1 receptor gene of the form (TG)n. This DNA polymorphism has 14 alleles and a heterozygosity of >0.8. We have used this DNA polymorphism to l ocalize the GLP-1 receptor gene within the genetic map of the short ar m of chromosome 6. This DNA polymorphism will facilitate genetic studi es of the contribution of the GLP-1 receptor gene to impaired beta-cel l function and NIDDM.