High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues

High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues
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DOI:
10.1101/gr.088120.108
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发表时间:
2009-06-01
期刊:
影响因子:
7
通讯作者:
Flint, Jonathan
Flint, Jonathan
中科院分区:
生物学1区
文献类型:
--
作者:
Huang, Guo-Jen;Shifman, Sagiv;Flint, Jonathan

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复杂表型的遗传变异的一部分是通过它们对基因表达的影响来实现的,因此复杂性状分析中的一个重要挑战是发现转录本丰度变化的遗传基础。到目前为止,在啮齿动物中定位数量性状基因座(QTL)和表达数量性状基因座(eQTL)的潜力受到近交系之间杂交固有的低定位分辨率的限制。我们提供了一个兆位分辨率的eQTL在海马,肺,肝脏样本的异质性股票(HS)小鼠,其中843个QTL也被定位在兆位分辨率的地图。我们利用密集的小鼠SNP数据表明,由于等位基因特异性杂交造成的伪影发生在30%的顺式作用eQTL中,通过与外显子表达数据的比较,我们表明基因39端的选择性剪接占了基因的30%。
A proportion of the genetic variants underlying complex phenotypes do so through their effects on gene expression, so an important challenge in complex trait analysis is to discover the genetic basis for the variation in transcript abundance. So far, the potential of mapping both quantitative trait loci (QTLs) and expression quantitative trait loci (eQTLs) in rodents has been limited by the low mapping resolution inherent in crosses between inbred strains. We provide a megabase resolution map of thousands of eQTLs in hippocampus, lung, and liver samples from heterogeneous stock (HS) mice in which 843 QTLs have also been mapped at megabase resolution. We exploit dense mouse SNP data to show that artifacts due to allele-specific hybridization occur in; 30% of the cis-acting eQTLs and, by comparison with exon expression data, we show that alternative splicing of the 39 end of the genes accounts for