Mouse genomic variation and its effect on phenotypes and gene regulation

作者：Thomas Keane, Leo Goodstadt, Petr Danecek, Michael A. White, Kim Wong, Binnaz Yalcin, Andreas Heger, Avigail Agam, Guy Slater, Martin Goodson, Nicholas A. Furlotte, Eleazar Eskin, Christoffer Nellåker, Helen Whitley, James Cleak, Deborah Janowitz, Polinka Hernandez-Pliego, Andrew Edwards, T. Grant Belgard, Peter L. Oliver, Rebecca E. McIntyre, Amarjit Bhomra, Jérôme Nicod, Xiangchao Gan, Yuan Wei, Louise van der Weyden, Charles A. Steward, Sendu Bala, Jim Stalker, Richard Mott, Richard Durbin, Ian J. Jackson, Anne Czechanski, José Afonso Guerra‐Assunção, Leah Rae Donahue, Laura G. Reinholdt, Bret A. Payseur, Chris P. Ponting, Ewan Birney, Jonathan Flint, David J. Adams · 发表于：Nature · 年份：2011 · DOI：10.1038/nature10413 · 被引用次数：1777 · 研究领域：Genetic Mapping and Diversity in Plants and Animals、Genetic diversity and population structure、Genomics and Phylogenetic Studies

We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism. The laboratory mouse has become the workhorse of biomedical research. The draft sequence of the mouse reference genome was published in 2002, but some forms of variation are still poorly documented. Two papers in this issue go a long way towards filling the gaps. The generation and analysis of sequence from 17 key mouse genomes, including most of the commonly used inbred strains and their progenitors, reveal extensive genetic variation and provide insights into the molecular nature of functional variants as well as the phylogenetic history of the lab mouse. The data will be an important resource for a new era of functional analysis. The second paper describes the landscape of structural variants in the genomes of 13 classical and four wild-derived inbred mou...