A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands
January 2002
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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.
- Humans
- Research Support, Non-U.S. Gov't
- Netherlands
- Genotype
- Genetic Markers
- Pedigree
- Alleles
- Chromosomes, Human, Pair 17
- Chromosomes, Human, Pair 11
- Genetic Predisposition to Disease
- Chromosomes, Human, Pair 6
- Chromosomes, Human, Pair 8
- *Linkage Disequilibrium
- Diabetes Mellitus, Type 1/*genetics
- HLA-DQ Antigens/genetics
- HLA-DR Antigens/genetics
- type 1 diabetes
- diabetes
- allele
- marker
- chromosome
- population
- patient
- region
- analysis
- trend
- 0 1 2
- linkage
- genet
- subject
- haplotype
- todd ja
- hla-dr
- frequency
- dr 4 allele
- susceptibility
