A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands
Type 1 diabetes has a substantial genetic component, with consistent evidence for a susceptibility locus in the HLA-DR/DQ region (chromosome 6p) and the insulin gene region (chromosome 11p). Genome scans have identified >18 other genomic regions that may harbor putative type 1 diabetes genes. However, evidence for most regions varies in different data sets. Given the genetic heterogeneity of type 1 diabetes, studies in homogeneous genetically isolated populations may be more successful in mapping susceptibility loci than in complex outbred populations. We describe a genome-wide search in a recently Dutch isolated population. We identified 43 patients that could be traced back to a common ancestor within 15 generations and performed a genome-wide scan using a combined linkage- and association-based approach. In addition to the HLA locus, evidence for type 1 diabetes loci was observed on chromosome 8q24 (marker D8S1128) and on chromosome 17q24 (marker D17S2059). Both the 8q and 17q localization are supported by allele-sharing at adjacent markers in affected individuals. Statistical evidence for a conserved ancestral haplotype was found for chromosome 8q24.
|Keywords||*Linkage Disequilibrium, Alleles, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 8, Diabetes Mellitus, Type 1/*genetics, Genetic Markers, Genetic Predisposition to Disease, Genotype, HLA-DQ Antigens/genetics, HLA-DR Antigens/genetics, Humans, Netherlands, Pedigree, Research Support, Non-U.S. Gov't|
Vaessen, N., Houwing-Duistermaat, J.J., Rademaker, T.A.M., Testers, L., Batstra, M.R., Sandkuijl, L.A., … Heutink, P.. (2002). A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands. Diabetes. Retrieved from http://hdl.handle.net/1765/9864