Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping

Genomics. 2006 Dec;88(6):719-730. doi: 10.1016/j.ygeno.2006.07.002. Epub 2006 Aug 17.

Abstract

To identify the disease-susceptibility genes of type 2 diabetes, we performed quantitative trait loci (QTL) analysis in F(2) populations generated from a BKS.Cg-m+/+Lepr(db) and C3H/HeJ intercross, taking advantage of genetically determined obesity and diabetes traits associated with the db gene. A genome-wide scan in the F(2) populations divided by sex and db genotypes identified 14 QTLs in total and 3 major QTLs on chromosome (Chr) 3 (LOD 5.78) for fat pad weight, Chr 15 (LOD 6.64) for body weight, and Chr 16 (LOD 8.15) for blood glucose concentrations. A linear-model-based genome scan using interactive covariates allowed us to consider sex- or sex-by db-specific effects of each locus. For the most significant QTL on Chr 16, the high-resolution haplotype comparison between BKS and C3H strains reduced the critical QTL interval from 20 to 4.6 Mb by excluding shared haplotype regions and identified 11 nonsynonymous single-nucleotide polymorphisms in six candidate genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping*
  • Crosses, Genetic
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Susceptibility
  • Female
  • Haplotypes / genetics*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci / genetics*