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

Jan Rozman, Birgit Rathkolb, Manuela A. Oestereicher, Christine Schütt, Aakash Chavan Ravindranath, Stefanie Leuchtenberger, Sapna Sharma, Martin Kistler, Monja Willershäuser, Robert Brommage, Terrence F. Meehan, Jeremy Mason, Hamed Haselimashhadi, Tertius Hough, Ann-Marie Mallon, Sara Wells, Luis Santos, Christopher J. Lelliott, Jacqueline K. White, Tania Sorg, Marie-France Champy, Lynette R. Bower, Corey L. Reynolds, Ann M. Flenniken, Stephen A. Murray, Lauryl M. J. Nutter, Karen L. Svenson, David West, Glauco P. Tocchini-Valentini, Arthur L. Beaudet, Fatima Bosch, Robert B. Braun, Michael S. Dobbie, Xiang Gao, Yann Herault, Ala Moshiri, Bret A. Moore, K. C. Lloyd, Colin McKerlie, Hiroshi Masuya, Nobuhiko Tanaka, Paul Flicek, Helen E. Parkinson, Radislav Sedlacek, Je Kyung Seong, Chi-Kuang Leo Wang, Mark Moore, Steve D. Brown, Matthias H. Tschöp, Wolfgang Wurst, Martin Klingenspor, Eckhard Wolf, Johannes Beckers, Fausto Machicao, Andreas Peter, Harald Staiger, Hans-Ulrich Häring, Harald Grallert, Monica Campillos, Holger Maier, Helmut Fuchs, Valerie Gailus-Durner, Thomas Werner and Martin Hrabe de Angelis ()
Additional contact information
Jan Rozman: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
Birgit Rathkolb: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
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)
Stefanie Leuchtenberger: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
Sapna Sharma: German Center for Diabetes Research (DZD)
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
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
Tania Sorg: CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS)
Marie-France Champy: CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS)
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
Stephen A. Murray: The Jackson Laboratory
Lauryl M. J. Nutter: The Centre for Phenogenomics
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
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)
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
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)
Wolfgang Wurst: Helmholtz Zentrum München, German Research Center for Environmental Health GmbH
Martin Klingenspor: Technical University of Munich, TUM School of Life Sciences Weihenstephan
Eckhard Wolf: German Center for Diabetes Research (DZD)
Johannes Beckers: Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
Fausto Machicao: Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen
Andreas Peter: German Center for Diabetes Research (DZD)
Harald Staiger: German Center for Diabetes Research (DZD)
Hans-Ulrich Häring: German Center for Diabetes Research (DZD)
Harald Grallert: German Center for Diabetes Research (DZD)
Monica Campillos: German Center for Diabetes Research (DZD)
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

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01995-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-01995-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01995-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().