這項研究通過對來自“1000 Genomes Project”的462個人的類淋巴母細(xì)胞系的信使RNA和微RNA進(jìn)行測序和深度分析來確定人類基因組中的調(diào)控變化,。分析顯示了影響絕大部分基因的調(diào)控的普遍存在的基因變化，其中轉(zhuǎn)錄結(jié)構(gòu)和表達(dá)水平的變化同樣普遍，但從遺傳上來說在很大程度上是獨立的,。對因果性調(diào)控變化的定性有助于了解調(diào)控和“功能喪失”變化的細(xì)胞機制，同時也說明可能存在與疾病相關(guān)的幾十個等位基因的假想因果性變異體,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Nature doi:10.1038/nature12531
Transcriptome and genome sequencing uncovers functional variation in humans
Tuuli Lappalainen, Michael Sammeth, Marc R. Friedländer, Peter A. C. ‘t Hoen, Jean Monlong, Manuel A. Rivas, Mar Gonzàlez-Porta, Natalja Kurbatova, Thasso Griebel, Pedro G. Ferreira, Matthias Barann, Thomas Wieland, Liliana Greger, Maarten van Iterson, Jonas Almlöf, Paolo Ribeca, Irina Pulyakhina, Daniela Esser, Thomas Giger, Andrew Tikhonov, Marc Sultan, Gabrielle Bertier, Daniel G. MacArthur, Monkol Lek, Esther Lizano, Henk P. J. Buermans, Ismael Padioleau, Thomas Schwarzmayr, Olof Karlberg, Halit Ongen, Helena Kilpinen, Sergi Beltran, Marta Gut, Katja Kahlem, Vyacheslav Amstislavskiy, Oliver Stegle, Matti Pirinen, Stephen B. Montgomery, Peter Donnelly, Mark I. McCarthy, Paul Flicek, Tim M. Strom, The Geuvadis Consortium, Hans Lehrach, Stefan Schreiber, Ralf Sudbrak, Ángel Carracedo, Stylianos E. Antonarakis, Robert Häsler, Ann-Christine Syvänen, Gert-Jan van Ommen, Alvis Brazma, Thomas Meitinger, Philip Rosenstiel, Roderic Guigó, Ivo G. Gut, Xavier Estivill & Emmanouil T. Dermitzakis
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.
