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.
Vaessen
Norbert
N
Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Heutink
Peter
P
Houwing-Duistermaat
Jeanine J
JJ
Snijders
Pieter J L M
PJ
Rademaker
Tessa
T
Testers
Leon
L
Batstra
Manou R
MR
Sandkuijl
Lodewijk A
LA
van Duijn
Cornelia M
CM
Oostra
Ben A
BA
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
D005819:Genetic Markers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens