A 2ND-GENERATION SCREEN OF THE HUMAN GENOME FOR SUSCEPTIBILITY TO INSULIN-DEPENDENT DIABETES-MELLITUS

During the past decade, the genetics of type 1 (insulin-dependent) dia betes mellitus (IDDM) has been studied extensively and the disorder ha s become a paradigm for genetically complex diseases. Previous genome screens(1,2) and studies focused on candidate genes(3-9) have provided evidence for genetic linkage between polymorphic DNA markers and 15 p utative IDDM susceptibility loci, designated IDDM1-IDDM15. We have car ried out a second-generation screen of the genome for linkage and anal ysed the data by multipoint linkage methods. An initial panel of 212 a ffected sibpairs (ASPs) was genotyped for 438 markers spanning all aut osomes, and an additional 467 ASPs were used for follow-up genotyping. Other than the well-established linkage with the HLA region at chromo some 6p21.3, there was only one region, located on chromosome Iq and n ot previously reported, where the log likelihood ratio (lod) was great er than 3. Lods between 1.0 and 1.8 were found in six other regions, t hree of which have been reported in other studies. Another reported re gion(10), on chromosome 6q and loosely linked to HLA, also had an elev ated led. Little or no support was found for most reported IDDM loci ( lods were less than 1), despite larger sample sizes in the present stu dy.