A GENOME-WIDE SEARCH FOR HUMAN TYPE-1 DIABETES SUSCEPTIBILITY GENES

We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescenc e-based technology and linkage analysis. In addition to IDDM1 (in the major histocompatibility complex on chromosome 6p21) and IDDM2 (in the insulin gene region on chromosome 11p15), eighteen different chromoso me regions showed some positive evidence of linkage to disease. Linkag es to chromosomes iio (IDDM4) and 6q (IDDM5) were confirmed by replica tion, and chromosome is may encode a fifth disease locus. There are pr obably no genes with large effects aside from IDDM1. Therefore polygen ic inheritance Is indicated, with a major locus at the major histocomp atibility complex.