Common polymorphic transcript variation in human disease
Common polymorphic transcript variation in human disease
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DOI：
10.1101/gr.083477.108
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发表时间：
2009-04-01
期刊：
影响因子：
7
通讯作者：
Xie, Xiaohui
中科院分区：
文献类型：
--
作者：
Fraser, Hunter B.;Xie, Xiaohui
人们认为大多数人基因在不同的细胞类型中表达不同的转录本同工型。然而，在同一细胞类型内的个体之间不同的多态性转录变异（PTV）的全部程度和功能后果是未知的。在这里，我们表明PTV在两个人群的B细胞中广泛存在。发现成千上万的外显子以可遗传的方式表达了多态外显子，其中超过1000个表现出与顺式中单核苷酸多态性（SNP）基因型的强相关性。与PTV相关的SNP显示出受到人类最近肯定选择的迹象，并且在最近的四种自身免疫性疾病的最新基因组关联研究中，它们也高度富含SNP。从这种疾病关联的重叠中，我们推断出PTV是八种常见多态性有助于疾病风险的可能机制。 PTV的目录将是解释未来疾病关联研究结果并了解人类表型差异的范围的宝贵资源。
Most human genes are thought to express different transcript isoforms in different cell types; however, the full extent and functional consequences of polymorphic transcript variation (PTV), which differ between individuals within the same cell type, are unknown. Here we show that PTV is widespread in B-cells from two human populations. Tens of thousands of exons were found to be polymorphically expressed in a heritable fashion, and over 1000 of these showed strong correlations with single nucleotide polymorphism (SNP) genotypes in cis. The SNPs associated with PTV display signs of having been subject to recent positive selection in humans, and they are also highly enriched for SNPs implicated by recent genome-wide association studies of four autoimmune diseases. From this disease-association overlap, we infer that PTV is the likely mechanism by which eight common polymorphisms contribute to disease risk. A catalog of PTV will be a valuable resource for interpreting results from future disease-association studies and understanding the spectrum of phenotypic differences among humans.