EVIDENCE FOR A TYPE-1 DIABETES SUSCEPTIBILITY LOCUS (IDDM10) ON HUMAN-CHROMOSOME 10P11-Q11

A region of linkage to type 1 diabetes has been defined on human chrom osome 10p11-q11 (IDDM10; P = 0.0007) using 236 UK and 76 US affected s ibpairs and al cM resolution microsatellite marker map, Analysis by th e transmission disequilibrium test (TDT) in 1159 families with at leas t one diabetic child, from the UK, the US, Norway, Sardinia and Italy provided additional support for linkage at D10S193 (P = 0.006, P-c = 0 .17), Notably, 5.1 cM distal to D10S193, marker D10S588 also provided positive TDT results (P = 0.009, P-c = 0.25) but the allele under anal ysis was also preferentially transmitted to nonaffected siblings (P = 0.0008, P-c = 0.02), This allele was positively associated in an indep endent UK case control study and, importantly, was neutrally transmitt ed in control CEPH families, These results suggest a type 1 diabetes s usceptibility locus on chromosome 10p11-q11 (provisionally designated IDDM10) and demonstrate the necessity of analysis of non affected sibl ings in disease families, as well as analysis of control families.