Genome-wide genetic association of complex traits in heterogeneous stock mice
Genome-wide genetic association of complex traits in heterogeneous stock mice
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DOI：
10.1038/ng1840
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发表时间：
2006-08-01
期刊：
影响因子：
30.8
通讯作者：
Flint, Jonathan
中科院分区：
文献类型：
--
作者：
Valdar, William;Solberg, Leah C.;Flint, Jonathan
数量性状基因座（QTL）的精细定位困难是小鼠复杂性状分子解剖进展的主要障碍。在这里，我们表明，全基因组高分辨率映射的多种表型可以实现使用股票的遗传异质性小鼠。我们开发了一个保守的和强大的bootstrap分析定位843个QTL，平均95%的置信区间为2.8 Mb。QTL导致97个性状的变异，包括人类疾病模型（哮喘、2型糖尿病、肥胖和焦虑）以及免疫学、生化学和血液学表型。几乎所有的表型的遗传结构是复杂的，许多位点，每个贡献的总方差的一小部分。我们的数据集可在http://gscan.well.ox.ac.uk上免费获得，为参与许多复杂性状的基因的功能表征提供了一个切入点。
Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.