Identification of candidate genes in the type 2 diabetes modifier locus using expression QTL

被引：34

作者：

Yaguchi, H

Togawa, K

Moritani, M

Itakura, M ^{[1
]}

机构：

[1] Univ Tokushima, Inst Genome Res, Div Genet Informat, Tokushima 7708503, Japan

[2] Otsuka Pharmaceut Factory Inc, Div Pharmacol, Tokushima 7728601, Japan

来源：

GENOMICS | 2005年 / 85卷 / 05期

基金：

日本学术振兴会;

关键词：

type; 2; diabetes; QTL analysis; expression QTL; candidate genes;

D O I：

10.1016/j.ygeno.2005.01.006

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

To identify new genetic determinants relevant to type 2 diabetes (T2D), diabetic F2 progeny were generated by intercrossing F1 mice obtained from a cross of BKS.Cg-Lepr(db)+/+m and DBA/2, and T2D-related phenotypes were measured. In the F2 population, increased susceptibility to diabetes and obesity was observed. We also detected the major quantitative trait loci (QTL) modifying the severity of diabetes on chromosome 9, where peaks of logarithm of odds (LOD) overlapped for three traits. To identify candidate genes in the QTL intervals, we combined "expression QTL:'(eQTL), taking mRNA levels as quantitative traits, and "interstrain sequence variations, including cSNPs." As a result, four genes were identified from cosegregation of clinical QTL with eQTL and 13 genes were found from interstrain cSNPs as candidates in the T2D modifier QTL. Our combined approach shows the acceleration of the discovery of candidate genes in the QTL of interest, spanning several megabases. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：591 / 599

页数：9

共 12 条

[1]

Bjorntorp Per, 1994, Current Opinion in Lipidology, V5, P166, DOI 10.1097/00041433-199405030-00003

[2]

BOOKOUT AL, 2003, NURSA E J

[3] Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice [J].