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-depend ent (type I) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) familie s with type 1 diabetes. Our analyses provided additional evidence for linka ge 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 betwe en D11S4205 and GALN. We also identified polymorphisms in two candidate gen es, Fas-associated death domain protein (FADD) and galanin (GALN). Analyses of the data by transmission/disequilibrium test (TDT) and extended TDT (ET DT) did not provide any evidence for association/linkage with these candida te genes. However. ETDT did reveal significant association/linkage with the marker D11S987 (P=0.0004) within the IDDM4 interval defined by ASP analyse s, suggesting that IDDM4 may be in the close proximity of D11S987.