Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family

J Clin Invest. 1998 Oct 15;102(8):1569-75. doi: 10.1172/JCI3379.

Abstract

Based on a genomic search for linkage, a locus contributing to type 1 diabetes in a large Bedouin Arab family (19 affected relatives) maps to the long arm of chromosome 10 (10q25; nonparametric linkage = 4.99; P = 0.00004). All affected relatives carry one or two high-risk HLA-DR3 haplotypes that are rarely found in other family members. One chromosome 10 haplotype, the B haplotype, was transmitted from a heterozygous parent to 13 of 13 affected offspring compared to 10 of 23 unaffected siblings. Recombination events occurring on this haplotype place the susceptibility locus in an 8-cM interval between markers D10S1750 and D10S1773. Two adjacent markers, D10S592 and D10S554, showed evidence of linkage disequilibrium with the disease locus. A 273-bp allele at D10S592 was transmitted to 8 of 10 affected offspring compared to 3 of 14 unaffected siblings, and a 151-bp allele at D10S554 was transmitted to 15 of 15 affected offspring compared with 10 of 24 unaffected siblings. D10S554 and D10S592 and the closest flanking markers are contained in a 1,240-kb yeast artificial chromosome, a region small enough to proceed with positional cloning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arabs*
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 10*
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease
  • HLA-DR3 Antigen / genetics*
  • Haplotypes
  • Humans
  • Israel
  • Pedigree
  • White People / genetics*

Substances

  • Genetic Markers
  • HLA-DR3 Antigen