Mapping diabetes QTL in an intercross derived from a congenic strain of the Brown Norway and Goto-Kakizaki rats

被引：13

作者：

Collins, Stephan C. ^{[1
]}

Wallis, Robert H. ^{[1
]}

Wilder, Steven P. ^{[1
]}

Wallace, Karin J. ^{[1
]}

Argoud, Karene ^{[1
]}

Kaisaki, Pamela J. ^{[1
]}

Bihoreau, Marie-Therese ^{[1
]}

Gauguier, Dominique ^{[1
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

来源：

MAMMALIAN GENOME | 2006年 / 17卷 / 06期

基金：

英国惠康基金;

关键词：

D O I：

10.1007/s00335-005-0168-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genetic studies in experimental crosses derived from the inbred Goto-Kakizaki (GK) rat model of spontaneous diabetes mellitus have identified quantitative trait loci (QTL) for diabetes phenotypes in a large region of rat Chromosome (RNO) 1. To test the impact of GK variants on QTL statistical and biological features, we combined genetic and physiologic studies in a cohort of F-2 hybrids derived from a QTL substitution congenic strain (QTLSCS) carrying a 110-cM GK haplotype of RNO1 introgressed onto the genetic background of the Brown Norway (BN) strain. Glucose intolerance and altered insulin secretion in QTLSCS rats when compared with BN controls were consistent with original QTL features in a GK x BN F-2 cross. Segregating GK alleles in the QTLSCS F-2 cross account for most of these phenotypic differences between QTLSCS and BN rats. However, significant QTL for diabetes traits in both the QTLSCS and GK x BN F-2 cohorts account for a similar small proportion of their variance. Comparing results from these experimental systems provides indirect estimates of the contribution of genetic interactions and environmental factors to QTL architecture as well as locus and biological targets for future post-QTL mapping studies in congenic substrains.

引用

页码：538 / 547

页数：10

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