High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping.
High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping.
复制标题
DOI：
10.1534/g3.115.020784
复制
发表时间：
2015-07-28
期刊：
影响因子：
--
通讯作者：
Lusis AJ
中科院分区：
文献类型：
--
作者：
Rau CD;Parks B;Wang Y;Eskin E;Simecek P;Churchill GA;Lusis AJ
人类全基因组关联研究已经确定了数千个与疾病表型相关的基因座。使用啮齿动物模型进行全基因组关联研究也是可行的，与人类研究相比，这些研究具有一些重要的优势，包括受控环境、获取组织进行分子图谱分析、可重现的基因类型，以及广泛的实验验证技术。与常见的小鼠近交系的关联映射通常需要100个或更多的品系才能达到足够的功率和映射分辨率；相比之下，用于人类研究的样本量通常比这大一个或多个数量级。为了在小鼠中进行强有力的研究，我们使用小鼠多样性阵列为∼175近交系小鼠创造了高密度基因类型。这些新数据将标记密度提高了1.9倍，减少了缺失率，并与以前的基因数据相比，提供了更准确的杂合区识别。我们报告了从先前报道的使用新的基因数据的关联图谱研究中发现了新的基因座。这些数据可以免费下载，基于Web的工具可以方便地访问关联地图和查看各个基因座的潜在强度数据。
Human genome-wide association studies have identified thousands of loci associated with disease phenotypes. Genome-wide association studies also have become feasible using rodent models and these have some important advantages over human studies, including controlled environment, access to tissues for molecular profiling, reproducible genotypes, and a wide array of techniques for experimental validation. Association mapping with common mouse inbred strains generally requires 100 or more strains to achieve sufficient power and mapping resolution; in contrast, sample sizes for human studies typically are one or more orders of magnitude greater than this. To enable well-powered studies in mice, we have generated high-density genotypes for ∼175 inbred strains of mice using the Mouse Diversity Array. These new data increase marker density by 1.9-fold, have reduced missing data rates, and provide more accurate identification of heterozygous regions compared with previous genotype data. We report the discovery of new loci from previously reported association mapping studies using the new genotype data. The data are freely available for download, and Web-based tools provide easy access for association mapping and viewing of the underlying intensity data for individual loci.