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 in | Nature (London) Vol. 477; no. 7364; pp. 289 - 294 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
15.09.2011
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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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| AbstractList | 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. We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known.Weuse 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. [PUBLICATION ABSTRACT] 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. |
| Audience | Academic |
| Author | Jackson, Ian J. Bhomra, Amarjit Czechanski, Anne Goodson, Martin Nellåker, Christoffer Eskin, Eleazar Durbin, Richard Guerra-Assunção, José Afonso Slater, Guy Birney, Ewan Oliver, Peter L. White, Michael A. Agam, Avigail Yalcin, Binnaz Reinholdt, Laura G. Danecek, Petr Yuan, Wei Adams, David J. Ponting, Chris P. Donahue, Leah Rae Cleak, James Flint, Jonathan Payseur, Bret A. Bala, Sendu McIntyre, Rebecca E. Stalker, Jim Furlotte, Nicholas A. Keane, Thomas M. Goodstadt, Leo Steward, Charles A. Mott, Richard Nicod, Jérôme Gan, Xiangchao Heger, Andreas Whitley, Helen Hernandez-Pliego, Polinka Wong, Kim van der Weyden, Louise Belgard, T. Grant Janowitz, Deborah Edwards, Andrew |
| AuthorAffiliation | 5 University of California, Los Angeles, California 90095-1596, USA 2 The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK 7 The Jackson Laboratory, Bar Harbor, Maine 04609, USA 6 Medical Research Council Human Genetics Unit, Crew Road, Edinburgh EH4 2XU, UK 8 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK 4 MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK 3 Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA 1 The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK |
| AuthorAffiliation_xml | – name: 1 The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – name: 7 The Jackson Laboratory, Bar Harbor, Maine 04609, USA – name: 8 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK – name: 5 University of California, Los Angeles, California 90095-1596, USA – name: 2 The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – name: 3 Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA – name: 6 Medical Research Council Human Genetics Unit, Crew Road, Edinburgh EH4 2XU, UK – name: 4 MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK |
| Author_xml | – sequence: 1 givenname: Thomas M. surname: Keane fullname: Keane, Thomas M. organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 2 givenname: Leo surname: Goodstadt fullname: Goodstadt, Leo organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 3 givenname: Petr surname: Danecek fullname: Danecek, Petr organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 4 givenname: Michael A. surname: White fullname: White, Michael A. organization: Laboratory of Genetics, University of Wisconsin – sequence: 5 givenname: Kim surname: Wong fullname: Wong, Kim organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 6 givenname: Binnaz surname: Yalcin fullname: Yalcin, Binnaz organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 7 givenname: Andreas surname: Heger fullname: Heger, Andreas organization: Department of Physiology, MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford – sequence: 8 givenname: Avigail surname: Agam fullname: Agam, Avigail organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK , Department of Physiology, MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford – sequence: 9 givenname: Guy surname: Slater fullname: Slater, Guy organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 10 givenname: Martin surname: Goodson fullname: Goodson, Martin organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 11 givenname: Nicholas A. surname: Furlotte fullname: Furlotte, Nicholas A. organization: University of California – sequence: 12 givenname: Eleazar surname: Eskin fullname: Eskin, Eleazar organization: University of California – sequence: 13 givenname: Christoffer surname: Nellåker fullname: Nellåker, Christoffer organization: Department of Physiology, MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford – sequence: 14 givenname: Helen surname: Whitley fullname: Whitley, Helen organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 15 givenname: James surname: Cleak fullname: Cleak, James organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 16 givenname: Deborah surname: Janowitz fullname: Janowitz, Deborah organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK , Department of Psychiatry and Psychotherapy, Ernst-Moritz-Arndt-Universität Greifswald Klinikum der Hansestadt Stralsund, Rostocker Chaussee 70, 18437 Stralsund, Germany – sequence: 17 givenname: Polinka surname: Hernandez-Pliego fullname: Hernandez-Pliego, Polinka organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 18 givenname: Andrew surname: Edwards fullname: Edwards, Andrew organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 19 givenname: T. Grant surname: Belgard fullname: Belgard, T. Grant organization: Department of Physiology, MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford – sequence: 20 givenname: Peter L. surname: Oliver fullname: Oliver, Peter L. organization: Department of Physiology, MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford – sequence: 21 givenname: Rebecca E. surname: McIntyre fullname: McIntyre, Rebecca E. organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 22 givenname: Amarjit surname: Bhomra fullname: Bhomra, Amarjit organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 23 givenname: Jérôme surname: Nicod fullname: Nicod, Jérôme organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 24 givenname: Xiangchao surname: Gan fullname: Gan, Xiangchao organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 25 givenname: Wei surname: Yuan fullname: Yuan, Wei organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 26 givenname: Louise surname: van der Weyden fullname: van der Weyden, Louise organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 27 givenname: Charles A. surname: Steward fullname: Steward, Charles A. organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 28 givenname: Sendu surname: Bala fullname: Bala, Sendu organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 29 givenname: Jim surname: Stalker fullname: Stalker, Jim organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 30 givenname: Richard surname: Mott fullname: Mott, Richard organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 31 givenname: Richard surname: Durbin fullname: Durbin, Richard organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK – sequence: 32 givenname: Ian J. surname: Jackson fullname: Jackson, Ian J. organization: Medical Research Council Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, UK – sequence: 33 givenname: Anne surname: Czechanski fullname: Czechanski, Anne organization: The Jackson Laboratory – sequence: 34 givenname: José Afonso surname: Guerra-Assunção fullname: Guerra-Assunção, José Afonso organization: European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK – sequence: 35 givenname: Leah Rae surname: Donahue fullname: Donahue, Leah Rae organization: The Jackson Laboratory – sequence: 36 givenname: Laura G. surname: Reinholdt fullname: Reinholdt, Laura G. organization: The Jackson Laboratory – sequence: 37 givenname: Bret A. surname: Payseur fullname: Payseur, Bret A. organization: Laboratory of Genetics, University of Wisconsin – sequence: 38 givenname: Chris P. surname: Ponting fullname: Ponting, Chris P. organization: Department of Physiology, MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford – sequence: 39 givenname: Ewan surname: Birney fullname: Birney, Ewan organization: European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK – sequence: 40 givenname: Jonathan surname: Flint fullname: Flint, Jonathan email: jf@well.ox.ac.uk organization: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK – sequence: 41 givenname: David J. surname: Adams fullname: Adams, David J. email: da1@sanger.ac.uk organization: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24500736$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21921910$$D View this record in MEDLINE/PubMed https://inserm.hal.science/inserm-03949307$$DView record in HAL |
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| Keywords | Vertebrata Phenotype Regulation(control) Mammalia Gene Mouse Nucleotide sequence Genomics Rodentia Strain |
| Language | English |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 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. |
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| Snippet | 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... We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known.Weuse these genomes to... |
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| Title | Mouse genomic variation and its effect on phenotypes and gene regulation |
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