GENETIC-MAPPING OF A SUSCEPTIBILITY LOCUS FOR INSULIN-DEPENDENT DIABETES-MELLITUS ON CHROMOSOME 11Q

LOCI in the major histocompatibility complex (MHC) on chromosome 6 and the insulin (INS) region on chromosome 11 have been implicated in susceptibility to insulin-dependent diabetes mellitus (IDDM) through candidate gene investigations(1-5), but they may account for less than 50% of genetic risk for the disease(6). Genome-wide linkage studies have led to localization of more than 10 susceptibility loci for insulin-dependent diabetes in the non-obese diabetic (NOD) mouse(7) and the BB rat(8). Similar studies are now possible in humans through the development of dense genetic maps of highly informative microsatellite loci obtained using polymerase chain reaction analysis(9). We have applied microsatellite markers from recent Genethon maps(10,11), and other highly informative markers, in a genome-wide linkage study in IDDM. Here we report evidence for the localization of a previously undetected susceptibility locus for IDDM in the region of the FGF3 gene on chromosome 11q. Our result shows the potential of genome-wide linkage studies to detect susceptibility loci in IDDM and other multifactorial disorders.