Mouse genomic variation and its effect on phenotypes and gene regulation

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...

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Published inNature (London) Vol. 477; no. 7364; pp. 289 - 294
Main Authors Keane, Thomas M., Goodstadt, Leo, Danecek, Petr, White, Michael A., Wong, Kim, Yalcin, Binnaz, Heger, Andreas, Agam, Avigail, Slater, Guy, Goodson, Martin, Furlotte, Nicholas A., Eskin, Eleazar, Nellåker, Christoffer, Whitley, Helen, Cleak, James, Janowitz, Deborah, Hernandez-Pliego, Polinka, Edwards, Andrew, Belgard, T. Grant, Oliver, Peter L., McIntyre, Rebecca E., Bhomra, Amarjit, Nicod, Jérôme, Gan, Xiangchao, Yuan, Wei, van der Weyden, Louise, Steward, Charles A., Bala, Sendu, Stalker, Jim, Mott, Richard, Durbin, Richard, Jackson, Ian J., Czechanski, Anne, Guerra-Assunção, José Afonso, Donahue, Leah Rae, Reinholdt, Laura G., Payseur, Bret A., Ponting, Chris P., Birney, Ewan, Flint, Jonathan, Adams, David J.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 15.09.2011
Nature Publishing Group
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Summary: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. Variation in the mouse genome 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 mouse strains, mapping many of them to base-pair resolution. Despite their prevalence, structural variants are shown to have a relatively small impact on phenotypic variation.
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PMCID: PMC3276836
Author Contributions D.J.A. and J.F. conceived the study, directed the research, and wrote the paper. T.M.K., P.D., L.G., B.P., M.W., K.W., B.Y., A.H., A.A., G.S., M.G., N.F., E.E., C.N., H.W., J.C., D.J., P.H.-P., A.B., J.N., X.G., W.Y., A.B., L.v.d.W., C.A.S., S.B., J.S., R.M., R.D., I.J., C.P.P. and E.B. performed data analysis. L.R., A.C. and L.D. provided essential biological resources.
Author Information Genomic structural variant study data is deposited in dbSNP (Handle: SC_MOUSE_GENOMES) and DGVA (estd118). Sequence accession numbers are provided in the Supplementary Information. Reprints and permissions information is available at www.nature.com/reprints. This paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence, and is freely available to all readers at www.nature.com/nature. The authors declare no competing financial interests. Readers are welcome to comment on the online version of this article at www.nature.com/nature.
These authors contributed equally to this work.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature10413