title: A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands.
abstract: 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.
authors.affiliation: Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vaessen
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: Pieter J L M
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Tessa
authors.initials: T
authors.lastname: Rademaker
authors.forename: Leon
authors.initials: L
authors.lastname: Testers
authors.forename: Manou R
authors.initials: MR
authors.lastname: Batstra
authors.forename: Lodewijk A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
mesh_terms: D000483:Alleles; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002896:Chromosomes, Human, Pair 6; D002898:Chromosomes, Human, Pair 8; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D009426:Netherlands; D010375:Pedigree
chemical_list: D005819:Genetic Markers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens