MULTIFACTORIAL INHERITANCE IN TYPE-1 DIABETES

To data, twelve separate chromosome regions have been implicated in th e development of human type 1 (insulin-dependent) diabetes mellitus. T he major disease locus, IDDM1 in the major histocompatibility complex (MHC) on chromosome 6p21, accounts for about 35% of the observed famil ial clustering and its contribution to disease susceptibility is likel y to involve polymorphic residues of class II molecules in T-cell-medi ated autoimmunity. IDDM2 is encoded by a minisatellite locus embedded in the 5' regulatory region of the insulin gene. Familial clustering o f disease can be explained by the sharing of alleles of at least 10 lo ci. IDDM1 and IDDM2 interact epistatically. For a multifactorial disea se, such as type 1 diabetes, important information concerning the path ways and mechanisms involved can be gained from examining such interac tions between loci, using methods that simultaneously take account of the joint effects of the various underlying genetic components.