Transcriptome and genome sequencing uncovers functional variation in humans.
Transcriptome and genome sequencing uncovers functional variation in humans.
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作者：
基因组测序项目正在人类中发现数百万种基因变异，而对其功能影响的解读对于理解人类性状变异的遗传基础至关重要。在此，我们报告了对来自千人基因组计划的462个人的淋巴母细胞系的mRNA和miRNA进行的测序及深度分析——这是首批来自具有高质量基因组序列的多个人群的统一处理的RNA测序数据。我们发现了极其广泛的基因变异影响着大多数基因的调控，转录本结构和表达水平的变异同样常见，但在遗传上基本相互独立。我们对因果调控变异的特征描述揭示了调控变异和功能丧失变异的细胞机制，并使我们能够推断出数十个疾病相关位点的假定因果变异。总之，这项研究提供了对转录组变异的细胞机制以及人类基因组中功能变异全貌的深入理解。
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 mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project – the first uniformly processed RNA-seq data from multiple human populations with high-quality genome sequences. We discovered extremely widespread genetic variation affecting regulation of the majority of genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on cellular mechanisms of regulatory and loss-of-function variation, and allowed 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.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
4.5
作者：
Lee Y;Gamazon ER;Rebman E;Lee Y;Lee S;Dolan ME;Cox NJ;Lussier YA
通讯作者：
Lussier YA
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
DOI：
10.1126/science.1215040
发表时间：
2012-02-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
MacArthur DG;Balasubramanian S;Frankish A;Huang N;Morris J;Walter K;Jostins L;Habegger L;Pickrell JK;Montgomery SB;Albers CA;Zhang ZD;Conrad DF;Lunter G;Zheng H;Ayub Q;DePristo MA;Banks E;Hu M;Handsaker RE;Rosenfeld JA;Fromer M;Jin M;Mu XJ;Khurana E;Ye K;Kay M;Saunders GI;Suner MM;Hunt T;Barnes IH;Amid C;Carvalho-Silva DR;Bignell AH;Snow C;Yngvadottir B;Bumpstead S;Cooper DN;Xue Y;Romero IG;1000 Genomes Project Consortium;Wang J;Li Y;Gibbs RA;McCarroll SA;Dermitzakis ET;Pritchard JK;Barrett JC;Harrow J;Hurles ME;Gerstein MB;Tyler-Smith C
通讯作者：
Tyler-Smith C