Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes
Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes
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DOI：
10.1038/ng2119
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发表时间：
2007-10-01
期刊：
影响因子：
30.8
通讯作者：
Blangero, John
中科院分区：
文献类型：
--
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
基因表达的量的差异被认为是导致个体间表型差异的原因。我们获取了圣安东尼奥家族心脏研究中1240名参与者的淋巴细胞样本的全基因组转录图谱。在检测到的19648个常染色体转录本中，85%的表达水平具有显著的遗传性。连锁分析以5%的错误发现率揭示了超过1000个顺式调控的转录本，并表明具有最显著连锁证据的表达数量性状基因座通常位于给定转录本的结构基因座处。为了强调这个大幅扩充的顺式调控转录本图谱对发现影响人类复杂性状的基因的有用性，我们以高密度脂蛋白胆固醇浓度作为具有临床重要性的表型为例，确定顺式调控的瓦宁1（VNN1）基因含有影响高密度脂蛋白胆固醇浓度的序列变异。
Quantitative differences in gene expression are thought to contribute to phenotypic differences between individuals. We generated genome-wide transcriptional profiles of lymphocyte samples from 1,240 participants in the San Antonio Family Heart Study. The expression levels of 85% of the 19,648 detected autosomal transcripts were significantly heritable. Linkage analysis uncovered > 1,000 cis-regulated transcripts at a false discovery rate of 5% and showed that the expression quantitative trait loci with the most significant linkage evidence are often located at the structural locus of a given transcript. To highlight the usefulness of this much- enlarged map of cis-regulated transcripts for the discovery of genes that influence complex traits in humans, as an example we selected high-density lipoprotein cholesterol concentration as a phenotype of clinical importance, and identified the cis-regulated vanin 1 (VNN1) gene as harboring sequence variants that influence high-density lipoprotein cholesterol concentrations.