Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping
Identification of diabetes susceptibility loci in db mice by combined quantitative trait loci analysis and haplotype mapping
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DOI：
10.1016/j.ygeno.2006.07.002
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发表时间：
2006-12-01
期刊：
影响因子：
4.4
通讯作者：
Itakura, Mitsuo
中科院分区：
文献类型：
--
作者：
Monitani, Maki;Togawa, Katsuhiko;Itakura, Mitsuo
为了鉴定2型糖尿病的疾病易感基因，我们利用与db基因相关的遗传决定的肥胖和糖尿病性状，在由BKS.Cg-m+/+Lepr（db）和C3 H/HeJ互交产生的F-2群体中进行了数量性状位点（QTL）分析。在按性别和db基因型划分的F1群体中进行全基因组扫描，共鉴定出14个QTL，其中3个主效QTL位于染色体（Chr）3（LOD 5.78）上，Chr 15（LOD 6.64）上，Chr 16（LOD 8.15）上，分别与脂肪垫重量、体重和血糖浓度有关。基于线性模型的基因组扫描，使用交互式协变量，使我们能够考虑性别或性别的DB特定的影响，每个位点，对于最显着的QTL的Chr 16，BKS和C3 H株之间的高分辨率单倍型比较减少了关键QTL的间隔从20到4.6 Mb，通过排除共享的单倍型区域，并确定了11个非同义单核苷酸多态性在6个候选基因。(c)2006年爱思唯尔公司All rights reserved.
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, 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. (c) 2006 Elsevier Inc. All rights reserved.