Fine-mapping of the type 1 diabetes locus (IDDM4) on chromosome 11q and evaluation of two candidate genes (FADD and GALN) by affected sibpair and linkage-disequilibrium analyses

Previous studies have identified a susceptibility region for insulin-dependent (type 1) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) families with type 1 diabetes. Our analyses provided additional evidence for linkage for IDDM4 (a peak LOD score of 3.4 at D11S913). The markers with strong linkage evidence are located within an interval of approximately 6 cM between D11S4205 and GALN. We also identified polymorphisms in two candidate genes, Fas-associated death domain protein (FADD) and galanin (GALN). Analyses of the data by transmission/disequilibrium test (TDT) and extended TDT (ETDT) did not provide any evidence for association/linkage with these candidate genes. However, ETDT did reveal significant association/linkage with the marker D11S987 (P=0.0004) within the IDDM4 interval defined by ASP analyses, suggesting that IDDM4 may be in the close proximity of D11S987.