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

Maki Moritani; Katsuhiko Togawa; Hiroshi Yaguchi; Yuka Fujita; Yuka Yamaguchi; Hiroshi Inoue; Naoyuki Kamatani; Mitsuo Itakura

doi:10.1016/j.ygeno.2006.07.002

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.

Authors

Maki Moritani¹, Katsuhiko Togawa², Hiroshi Yaguchi³, Yuka Fujita¹, Yuka Yamaguchi¹, Hiroshi Inoue¹, Naoyuki Kamatani⁴, Mitsuo Itakura⁵

Affiliations

¹ Division of Genetic Information, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan.
² Division of Genetic Information, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan; First Institute of New Drug Discovery, Otsuka Pharmaceutical, Inc., Tokushima 771-0192, Japan.
³ Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto 772-8601, Japan.
⁴ Division of Statistical Genetics, Department of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
⁵ Division of Genetic Information, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan. Electronic address: itakura@genome.tokushima-u.ac.jp.

PMID: 16919419
DOI: 10.1016/j.ygeno.2006.07.002

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*