A Genome-Wide Search for Linkage-Disequilibrium With Type 1 Diabetes in a Recent Genetically Isolated Population From the Netherlands
- Norbert Vaessen1,
- Peter Heutink1,
- Jeanine J. Houwing-Duistermaat1,
- Pieter J.L.M. Snijders1,
- Tessa Rademaker1,
- Leon Testers1,
- Manou R. Batstra2,
- Lodewijk A. Sandkuijl1,
- Cornelia M. van Duijn1 and
- Ben A. Oostra1
- 1Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
- 2Department of Pediatrics, Erasmus Medical Center Rotterdam, Rotterdam, 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.
Footnotes
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Address correspondence and reprint requests to Prof. Dr. B.A. Oostra, Genetic Epidemiology Unit, Department of Clinical Genetics, Erasmus Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands. E-mail: oostra{at}kgen.fgg.eur.nl.
Received for publication 29 June 2001 and accepted in revised form 15 November 2001.
- DIABETES
