Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
Nature. 2013 Sep 26;501(7468):506-11. doi: 10.1038/nature12531. Epub 2013 Sep 15.
Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project--the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.
基因组测序项目正在发现数以百万计的人类遗传变异，而对其功能效应的解释对于理解人类特征变异的遗传基础至关重要。在这里，我们报告了来自 1000 基因组计划的 462 个人的淋巴母细胞系的信使 RNA 和 microRNA 的测序和深度分析——这是第一个来自多个具有高质量基因组序列的人类群体的统一处理的高通量 RNA-seq 数据。我们发现了极其广泛的遗传变异，影响了大多数基因的调控，转录结构和表达水平的变异同样常见，但在遗传上基本独立。我们对因果调节变异的特征描述揭示了调节和功能丧失变异的细胞机制，并使我们能够推断数十个与疾病相关的基因座的潜在因果变异。总的来说，这项研究深入了解了转录组变异的细胞机制以及人类基因组中功能变异的全景。
