IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-017-01995-2.html
   My bibliography  Save this article

Identification of genetic elements in metabolism by high-throughput mouse phenotyping

Author

Listed:
  • Jan Rozman

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Birgit Rathkolb

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Center for Diabetes Research (DZD)
    Ludwig-Maximilians-Universität München, Gene Center, Institute of Molecular Animal Breeding and Biotechnology)

  • Manuela A. Oestereicher

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Christine Schütt

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Aakash Chavan Ravindranath

    (German Center for Diabetes Research (DZD)
    Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Stefanie Leuchtenberger

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Sapna Sharma

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München)

  • Martin Kistler

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Monja Willershäuser

    (Technical University of Munich, TUM School of Life Sciences Weihenstephan
    Technical University of Munich
    Technical University of Munich)

  • Robert Brommage

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Terrence F. Meehan

    (European Bioinformatics Institute, Wellcome Genome Campus, Hinxton)

  • Jeremy Mason

    (European Bioinformatics Institute, Wellcome Genome Campus, Hinxton)

  • Hamed Haselimashhadi

    (European Bioinformatics Institute, Wellcome Genome Campus, Hinxton)

  • Tertius Hough

    (Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre))

  • Ann-Marie Mallon

    (Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre))

  • Sara Wells

    (Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre))

  • Luis Santos

    (Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre))

  • Christopher J. Lelliott

    (Wellcome Genome Campus, Hinxton)

  • Jacqueline K. White

    (Wellcome Genome Campus, Hinxton
    The Jackson Laboratory)

  • Tania Sorg

    (CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS)
    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Parc d’innovation
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964)

  • Marie-France Champy

    (CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS)
    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Parc d’innovation
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964)

  • Lynette R. Bower

    (University of California)

  • Corey L. Reynolds

    (Baylor College of Medicine, 7702 Main St, Houston Medical Center)

  • Ann M. Flenniken

    (The Centre for Phenogenomics
    The Hospital for Sick Children
    Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex)

  • Stephen A. Murray

    (The Jackson Laboratory)

  • Lauryl M. J. Nutter

    (The Centre for Phenogenomics
    The Hospital for Sick Children)

  • Karen L. Svenson

    (The Jackson Laboratory)

  • David West

    (Children’s Hospital Oakland Research Institute)

  • Glauco P. Tocchini-Valentini

    (Adriano Buzzati-Traverso Campus)

  • Arthur L. Beaudet

    (The Centre for Phenogenomics
    The Hospital for Sick Children)

  • Fatima Bosch

    (Universitat Autònoma de Barcelona)

  • Robert B. Braun

    (The Jackson Laboratory)

  • Michael S. Dobbie

    (Australian National University)

  • Xiang Gao

    (Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University)

  • Yann Herault

    (CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS)
    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Parc d’innovation
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964)

  • Ala Moshiri

    (School of Medicine, U.C. Davis)

  • Bret A. Moore

    (School of Veterinary Medicine, U.C. Davis)

  • K. C. Lloyd

    (University of California)

  • Colin McKerlie

    (The Centre for Phenogenomics
    The Hospital for Sick Children)

  • Hiroshi Masuya

    (RIKEN BioResource Center)

  • Nobuhiko Tanaka

    (RIKEN BioResource Center)

  • Paul Flicek

    (European Bioinformatics Institute, Wellcome Genome Campus, Hinxton)

  • Helen E. Parkinson

    (European Bioinformatics Institute, Wellcome Genome Campus, Hinxton)

  • Radislav Sedlacek

    (Institute of Molecular Genetics)

  • Je Kyung Seong

    (Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University)

  • Chi-Kuang Leo Wang

    (National Applied Research Laboratories (NARLabs))

  • Mark Moore

    (IMPC)

  • Steve D. Brown

    (Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre))

  • Matthias H. Tschöp

    (German Center for Diabetes Research (DZD)
    German Research Center for Environmental Health (GmbH)
    Technische Universität München)

  • Wolfgang Wurst

    (Helmholtz Zentrum München, German Research Center for Environmental Health GmbH
    Technische Universität München
    Deutsches Institut für Neurodegenerative Erkrankungen (DZNE) Site Munich
    Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München)

  • Martin Klingenspor

    (Technical University of Munich, TUM School of Life Sciences Weihenstephan
    Technical University of Munich
    Technical University of Munich)

  • Eckhard Wolf

    (German Center for Diabetes Research (DZD)
    Ludwig-Maximilians-Universität München, Gene Center, Institute of Molecular Animal Breeding and Biotechnology)

  • Johannes Beckers

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Center for Diabetes Research (DZD)
    School of Life Science Weihenstephan, Technische Universität München)

  • Fausto Machicao

    (Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen)

  • Andreas Peter

    (German Center for Diabetes Research (DZD)
    Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen
    Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen)

  • Harald Staiger

    (German Center for Diabetes Research (DZD)
    Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen
    Eberhard Karls University Tübingen)

  • Hans-Ulrich Häring

    (German Center for Diabetes Research (DZD)
    Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen
    Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tuebingen)

  • Harald Grallert

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München
    Clinical Cooperation Group Type 2 Diabetes, Helmholtz Zentrum München and Ludwig-Maximilians Universität München)

  • Monica Campillos

    (German Center for Diabetes Research (DZD)
    Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Holger Maier

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Helmut Fuchs

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Valerie Gailus-Durner

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Thomas Werner

    (University of Michigan)

  • Martin Hrabe de Angelis

    (Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Center for Diabetes Research (DZD)
    School of Life Science Weihenstephan, Technische Universität München)

Abstract

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

Suggested Citation

  • Jan Rozman & Birgit Rathkolb & Manuela A. Oestereicher & Christine Schütt & Aakash Chavan Ravindranath & Stefanie Leuchtenberger & Sapna Sharma & Martin Kistler & Monja Willershäuser & Robert Brommage, 2018. "Identification of genetic elements in metabolism by high-throughput mouse phenotyping," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-01995-2
    DOI: 10.1038/s41467-017-01995-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01995-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01995-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-01995-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.