SUSCEPTIBILITY TO HUMAN TYPE-1 DIABETES AT IDDM2 IS DETERMINED BY TANDEM REPEAT VARIATION AT THE INSULIN GENE MINISATELLITE LOCUS

The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisate llite or variable number of tandem repeats (VNTR) locus on human chrom osome 11p15.5. By 'cross-match' haplotype analysis and linkage disequi librium mapping, we have mapped the mutation IDDM2 to within the VNTR itself. Other polymorphisms were systematically excluded as primary di sease determinants. Transmission of IDDM2 may be influenced by parent- of-origin phenomena. Although we show that the insulin gene is express ed biallelically in the adult pancreas, we present preliminary evidenc e that the level of transcription in vivo is correlated with allelic v ariation within the VNTR. Allelic variation at VNTRs may play an impor tant general role in human disease.