Valdar William, Solberg Leah C, Gauguier Dominique, Burnett Stephanie, Klenerman Paul, Cookson William O, Taylor Martin S, Rawlins J Nicholas P, Mott Richard, Flint Jonathan
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Nat Genet. 2006 Aug;38(8):879-87. doi: 10.1038/ng1840. Epub 2006 Jul 9.
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.
精细定位数量性状基因座（QTL）的困难是阻碍小鼠复杂性状分子解析取得进展的主要障碍。在此，我们表明使用一组遗传异质性小鼠能够实现多种表型的全基因组高分辨率定位。我们开发了一种保守且稳健的自助法分析，以定位843个QTL，其平均95%置信区间为2.8兆碱基对。这些QTL导致了97种性状的变异，包括人类疾病模型（哮喘、2型糖尿病、肥胖症和焦虑症）以及免疫学、生物化学和血液学表型。几乎所有表型的遗传结构都很复杂，许多基因座各自对总方差的贡献较小。我们的数据集可在http://gscan.well.ox.ac.uk免费获取，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。
