The HOXD8 locus (2q31) is linked to type I diabetes. Interaction with chromosome 6 and 11 disease susceptibility genes.
Type I diabetes susceptibility genes have been identified within the major histocompatibility complex (MHC) on chromosome 6p21.3 and near the VNTR/insulin region on chromosome 11p15.5. We have used polymorphic dinucleotide repeat markers to search the human genome for additional susceptibility genes in 162 type I diabetic families with an affected sibling pair. We report that an additional susceptibility gene is located on chromosome 2q31 near HOXD8 (P < 10(-5), maximum logarithm of odds score = 4.8) in an analysis of affected sibling pairs having specific human leukocyte antigen (HLA) and hypervariable nucleotide tandem repeat (VNTR)/insulin gene haplotypes (absence of high-risk HLA-DR3/4 haplotypes and presence of homozygous high-risk class I VNTR alleles). These results suggest the interaction of a minimum of three genes in the pathogenesis of type I diabetes in humans.
Owerbach
D
D
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
Gabbay
K H
KH
D000483:Alleles; D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005192:Family Health; D005801:Genes, Homeobox / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans