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Mouse genomic variation and its effect on phenotypes and gene regulation

Author

Listed:
  • Thomas M. Keane

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Leo Goodstadt

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Petr Danecek

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Michael A. White

    (Laboratory of Genetics, University of Wisconsin)

  • Kim Wong

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Binnaz Yalcin

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Andreas Heger

    (MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford)

  • Avigail Agam

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
    MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford)

  • Guy Slater

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Martin Goodson

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Nicholas A. Furlotte

    (University of California)

  • Eleazar Eskin

    (University of California)

  • Christoffer Nellåker

    (MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford)

  • Helen Whitley

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • James Cleak

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Deborah Janowitz

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK
    Ernst-Moritz-Arndt-Universität Greifswald Klinikum der Hansestadt Stralsund, Rostocker Chaussee 70, 18437 Stralsund, Germany)

  • Polinka Hernandez-Pliego

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Andrew Edwards

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • T. Grant Belgard

    (MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford)

  • Peter L. Oliver

    (MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford)

  • Rebecca E. McIntyre

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Amarjit Bhomra

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Jérôme Nicod

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Xiangchao Gan

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Wei Yuan

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Louise van der Weyden

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Charles A. Steward

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Sendu Bala

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Jim Stalker

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Richard Mott

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • Richard Durbin

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

  • Ian J. Jackson

    (Medical Research Council Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, UK)

  • Anne Czechanski

    (The Jackson Laboratory)

  • José Afonso Guerra-Assunção

    (European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK)

  • Leah Rae Donahue

    (The Jackson Laboratory)

  • Laura G. Reinholdt

    (The Jackson Laboratory)

  • Bret A. Payseur

    (Laboratory of Genetics, University of Wisconsin)

  • Chris P. Ponting

    (MRC Functional Genomics Unit, Anatomy and Genetics, University of Oxford)

  • Ewan Birney

    (European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK)

  • Jonathan Flint

    (The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK)

  • David J. Adams

    (The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK)

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.

Suggested Citation

  • Thomas M. 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 & Chris, 2011. "Mouse genomic variation and its effect on phenotypes and gene regulation," Nature, Nature, vol. 477(7364), pages 289-294, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7364:d:10.1038_nature10413
    DOI: 10.1038/nature10413
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    Cited by:

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    2. Wei Sun & Yufeng Liu & James J. Crowley & Ting-Huei Chen & Hua Zhou & Haitao Chu & Shunping Huang & Pei-Fen Kuan & Yuan Li & Darla Miller & Ginger Shaw & Yichao Wu & Vasyl Zhabotynsky & Leonard McMill, 2015. "IsoDOT Detects Differential RNA-Isoform Expression/Usage With Respect to a Categorical or Continuous Covariate With High Sensitivity and Specificity," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 110(511), pages 975-986, September.
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    5. Antonio Lentini & Huaitao Cheng & J. C. Noble & Natali Papanicolaou & Christos Coucoravas & Nathanael Andrews & Qiaolin Deng & Martin Enge & Björn Reinius, 2022. "Elastic dosage compensation by X-chromosome upregulation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Moe Matsuzawa & Tomoaki Ando & Saaya Fukase & Meiko Kimura & Yasuharu Kume & Takuma Ide & Kumi Izawa & Ayako Kaitani & Mutsuko Hara & Eri Nakamura & Anna Kamei & Akira Matsuda & Nobuhiro Nakano & Keik, 2023. "The protective role of conjunctival goblet cell mucin sialylation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Teresa Robert-Finestra & Beatrice F. Tan & Hegias Mira-Bontenbal & Erika Timmers & Cristina Gontan & Sarra Merzouk & Benedetto Daniele Giaimo & François Dossin & Wilfred F. J. IJcken & John W. M. Mart, 2021. "SPEN is required for Xist upregulation during initiation of X chromosome inactivation," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    8. Patricia Gerdes & Sue Mei Lim & Adam D. Ewing & Michael R. Larcombe & Dorothy Chan & Francisco J. Sanchez-Luque & Lucinda Walker & Alexander L. Carleton & Cini James & Anja S. Knaupp & Patricia E. Car, 2022. "Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Markus Grosch & Laura Schraft & Adrian Chan & Leonie Küchenhoff & Kleopatra Rapti & Anne-Maud Ferreira & Julia Kornienko & Shengdi Li & Michael H. Radke & Chiara Krämer & Sandra Clauder-Münster & Emer, 2023. "Striated muscle-specific base editing enables correction of mutations causing dilated cardiomyopathy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. Stamatis Papathanasiou & Styliani Markoulaki & Logan J. Blaine & Mitchell L. Leibowitz & Cheng-Zhong Zhang & Rudolf Jaenisch & David Pellman, 2021. "Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    11. Afonso R. M. Almeida & João L. Neto & Ana Cachucho & Mayara Euzébio & Xiangyu Meng & Rathana Kim & Marta B. Fernandes & Beatriz Raposo & Mariana L. Oliveira & Daniel Ribeiro & Rita Fragoso & Priscila , 2021. "Interleukin-7 receptor α mutational activation can initiate precursor B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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