A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands

Diabetes. 2002 Mar;51(3):856-9. doi: 10.2337/diabetes.51.3.856.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Linkage Disequilibrium*
  • Netherlands
  • Pedigree

Substances

  • Genetic Markers
  • HLA-DQ Antigens
  • HLA-DR Antigens