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首页> 外文期刊>Genomics >Integrating QTL and high-density SNP analyses in mice to identify Insig2 as a susceptibility gene for plasma cholesterol levels.
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Integrating QTL and high-density SNP analyses in mice to identify Insig2 as a susceptibility gene for plasma cholesterol levels.

机译：在小鼠中整合QTL和高密度SNP分析，以鉴定Insig2是血浆胆固醇水平的易感基因。

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摘要

The use of inbred strains of mice to dissect the genetic complexity of common diseases offers a viable alternative to human studies, given the control over experimental parameters that can be exercised. Central to efforts to map susceptibility loci for common diseases in mice is a comprehensive map of DNA variation among the common inbred strains of mice. Here we present one of the most comprehensive high-density, single nucleotide polymorphism (SNP) maps of mice constructed to date. This map consists of 10,350 SNPs genotyped in 62 strains of inbred mice. We demonstrate the utility of these data via a novel integrative genomics approach to mapping susceptibility loci for complex traits. By integrating in silico quantitative trait locus (QTL) mapping with progressive QTL mapping strategies in segregating mouse populations that leverage large-scale mapping of the genetic determinants of gene expression traits, we not only facilitate identification of candidate quantitative trait genes, but also protect against spurious associations that can arise in genetic association studies due to allelic association among unlinked markers. Application of this approach to our high-density SNP map and two previously described F2 crosses between strains C57BL/6J (B6) and DBA/2J and between B6 ApoE(-/-) and C3H/HeJ ApoE(-/-) results in the identification of Insig2 as a strong candidate susceptibility gene for total plasma cholesterol levels.
机译：考虑到可以对实验参数进行控制，使用小鼠的近交系来解剖常见疾病的遗传复杂性为人类研究提供了可行的选择。绘制小鼠常见疾病易感基因座的核心工作是绘制小鼠常见近交品系中DNA变异的综合图。在这里，我们介绍了迄今为止构建的小鼠最全面的高密度，单核苷酸多态性（SNP）图。该图由62个近交系小鼠中的10,350个SNP基因型组成。我们通过新颖的综合基因组学方法来证明这些数据的实用性，以绘制复杂性状的易感基因座。通过将计算机定量性状基因座（QTL）定位与渐进式QTL定位策略整合在一起，在分离的小鼠种群中利用基因表达性状的遗传决定因素的大规模定位，我们不仅可以帮助鉴定候选的数量性状基因，而且还可以防止由于未连锁标记之间的等位基因关联，在遗传关联研究中可能会出现虚假关联。这种方法在我们的高密度SNP图上的应用以及菌株C57BL / 6J（B6）和DBA / 2J之间以及B6 ApoE（-/-）和C3H / HeJ ApoE（-/-）之间两个先前描述的F2杂交导致Insig2作为总血浆胆固醇水平的强候选易感基因的鉴定。

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