Identification of genetic elements in metabolism by high-throughput mouse phenotyping
Rozman, Jan (German Center for Diabetes Research)
Rathkolb, Birgit (Ludwig Maximilians Universität München. Institute of Molecular Animal Breeding and Biotechnology)
Oestereicher, Manuela A. (Helmholtz Zentrum München. Institute of Experimental Genetics)
Schütt, Christine (Helmholtz Zentrum München. Institute of Experimental Genetics)
Ravindranath, Aakash Chavan (Helmholtz Zentrum München. Institute of Bioinformatics and Systems Biology)
Leuchtenberger, Stefanie (Helmholtz Zentrum München. Institute of Experimental Genetics)
Sharma, Sapna (Helmholtz Zentrum München. Institute of Epidemiology II)
Kistler, Martin (Helmholtz Zentrum München. Institute of Experimental Genetics)
Willershäuser, Monja (Technical University of Munich. Institute for Food and Health)
Brommage, Robert (Helmholtz Zentrum München. Institute of Experimental Genetics)
Meehan, Terrence F. (European Bioinformatics Institute)
Mason, Jeremy (European Bioinformatics Institute)
Haselimashhadi, Hamed (European Bioinformatics Institute)
Hough, Tertius (Medical Research Council Harwell)
Mallon, Ann-Marie (Medical Research Council Harwell)
Wells, Sara (Medical Research Council Harwell)
Santos, Luis (Medical Research Council Harwell)
Lelliott, Christopher J. (Wellcome Trust Sanger Institute (Regne Unit))
White, Jacqueline K. (The Jackson Laboratory)
Sorg, Tania (Université de Strasbourg)
Champy, Marie-France (Université de Strasbourg)
Bower, Lynette R. (University of California. Mouse Biology Program)
Reynolds, Corey L. (Baylor College of Medicine. Department of Molecular and Human Genetics)
Flenniken, Ann M. (Mount Sinai Hospital)
Murray, Stephen A. (The Jackson Laboratory)
Nutter, Lauryl M. J. (The Hospital for Sick Children)
Svenson, Karen L. (The Jackson Laboratory)
West, David (Children's Hospital Oakland Research Institute)
Tocchini-Valentini, Glauco P. (Monterotondo Mouse Clinic. Institute of Cell Biology and Neurobiology)
Beaudet, Arthur L. (The Hospital for Sick Children)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Braun, Robert B. (The Jackson Laboratory)
Dobbie, Michael S. (Australian National University)
Gao, Xiang (Nanjing University. Collaborative Innovation Center for Genetics and Development)
Herault, Yann (Université de Strasbourg)
Moshiri, Ala (School of Medicine U.C. Davis. Department of Ophthalmology and Vision Science)
Moore, Bret A. (School of Veterinary Medicine U.C. Davis)
Lloyd, Kent (University of California)
McKerlie, Colin (The Hospital for Sick Children)
Masuya, Hiroshi (RIKEN BioResource Center)
Tanaka, Nobuhiko (RIKEN BioResource Center)
Flicek, Paul (European Bioinformatics Institute)
Parkinson, Helen E. (European Bioinformatics Institute)
Sedlacek, Radislav (Institute of Molecular Genetics. Czech Centre for Phenogenomics)
Seong, Je Kyung (Seoul National University. College of Veterinary Medicine)
Wang, Chi-Kuang Leo (National Laboratory Animal Center)
Moore, Mark (International Mouse Phenotyping Consortium)
Brown, Steve D. M (Medical Research Council Harwell)
Tschöp, Matthias H. (Technische Universität München. Department of Medicine)
Wurst, Wolfgang (Ludwig Maximilians Universität München. Adolf Butenandt Institut)
Klingenspor, Martin (Technical University of Munich. Institute for Food & Health)
Wolf, Eckhard (Ludwig Maximilians Universität München. Institute of Molecular Animal Breeding and Biotechnology)
Beckers, Johannes (Technische Universität München. School of Life Science Weihenstephan)
Machicao, Fausto (University of Tübingen. Department of Internal Medicine)
Peter, Andreas (Eberhard Karls University of Tuebingen. Institute for Diabetes Research and Metabolic Diseases)
Staiger, Harald (Eberhard Karls University Tübingen. Department of Pharmacy and Biochemistry)
Häring, Hans-Ulrich (Eberhard Karls University of Tuebingen. Institute for Diabetes Research and Metabolic Diseases)
Grallert, Harald (Ludwig-Maximilians-Universität München)
Campillos, Monica (Helmholtz Zentrum München. Institute of Bioinformatics and Systems Biology)
Maier, Holger (Helmholtz Zentrum München. Institute of Experimental Genetics)
Fuchs, Helmut (Helmholtz Zentrum München. Institute of Experimental Genetics)
Gailus-Durner, Valerie (Helmholtz Zentrum München. Institute of Experimental Genetics)
Werner, Thomas (University of Michigan. Internal Medicine Nephrology and Center for Computational Medicine and Bioinformatics)
De Angelis, Martin Hrabe (Technische Universität München. School of Life Science Weihenstephan)

Data:	2018
Resum:	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.
Ajuts:	European Commission 653961 European Commission 261492
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nature communications, Vol. 9 (January 2018) , art. 288, ISSN 2041-1723

DOI: 10.1038/s41467-017-01995-2
PMID: 29348434

16 p, 2.3 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats