Genome wide association analysis in a mouse advanced intercross line
Genome wide association analysis in a mouse advanced intercross line
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DOI：
10.1038/s41467-018-07642-8
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发表时间：
2018-12-04
影响因子：
16.6
通讯作者：
Palmer, Abraham A.
中科院分区：
文献类型：
--
作者：
Gonzales, Natalia M.;Seo, Jungkyun;Palmer, Abraham A.
LG/J × SM/J高级杂交系（LG × SM AIL）是一个多代远交群体。高等位基因频率，简单的遗传背景，以及完全测序的LG和SM基因组使其成为全基因组关联研究的强大群体。在这里，我们使用1063只AIL小鼠来确定与人类健康和疾病相关的50个特征的126个显著关联。我们还在200只小鼠的海马、纹状体和前额皮质中发现了数千个顺式和反式eqtl。我们复制了运动活动和Csmd1之间的关联，这是我们在早一代的AIL中发现的，并表明Csmd1突变小鼠再现了运动表型。我们的结果证明了LG x SM AIL作为一个定位群体的效用，确定了许多新的关联，并阐明了哺乳动物行为的遗传结构。
The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands of cis- and trans-eQTLs in the hippocampus, striatum, and prefrontal cortex of similar to 200 mice. We replicate an association between locomotor activity and Csmd1, which we identified in an earlier generation of this AIL, and show that Csmd1 mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.