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Identification of genetic elements in metabolism by high-throughput mouse phenotyping.
Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A; Schütt, Christine; Ravindranath, Aakash Chavan; Leuchtenberger, Stefanie; Sharma, Sapna; Kistler, Martin; Willershäuser, Monja; Brommage, Robert; Meehan, Terrence F; Mason, Jeremy; Haselimashhadi, Hamed; Hough, Tertius; Mallon, Ann-Marie; Wells, Sara; Santos, Luis; Lelliott, Christopher J; White, Jacqueline K; Sorg, Tania; Champy, Marie-France; Bower, Lynette R; Reynolds, Corey L; Flenniken, Ann M; Murray, Stephen A; Nutter, Lauryl M J; Svenson, Karen L; West, David; Tocchini-Valentini, Glauco P; Beaudet, Arthur L; Bosch, Fatima; Braun, Robert B; Dobbie, Michael S; Gao, Xiang; Herault, Yann; Moshiri, Ala; Moore, Bret A; Kent Lloyd, K C; McKerlie, Colin; Masuya, Hiroshi; Tanaka, Nobuhiko; Flicek, Paul; Parkinson, Helen E; Sedlacek, Radislav; Seong, Je Kyung; Wang, Chi-Kuang Leo; Moore, Mark; Brown, Steve D; Tschöp, Matthias H; Wurst, Wolfgang.
Afiliação
  • Rozman J; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Rathkolb B; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Oestereicher MA; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Schütt C; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Ravindranath AC; Ludwig-Maximilians-Universität München, Gene Center, Institute of Molecular Animal Breeding and Biotechnology, Feodor-Lynen Strasse 25, 81377, Munich, Germany.
  • Leuchtenberger S; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Sharma S; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Kistler M; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Willershäuser M; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Brommage R; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Meehan TF; German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Mason J; Research Unit of Molecular Epidemiology, Institute of Epidemiology II, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Haselimashhadi H; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Hough T; EKFZ - Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, 85354, Freising, Germany.
  • Mallon AM; ZIEL - Institute for Food & Health, Technical University of Munich, 85354, Freising, Germany.
  • Wells S; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.
  • Santos L; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
  • Lelliott CJ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
  • White JK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
  • Champy MF; Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Oxfordshire, OX11 0RD, UK.
  • Bower LR; Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Oxfordshire, OX11 0RD, UK.
  • Reynolds CL; Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Oxfordshire, OX11 0RD, UK.
  • Flenniken AM; Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Oxfordshire, OX11 0RD, UK.
  • Murray SA; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Nutter LMJ; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Svenson KL; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
  • West D; CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), 1 Rue Laurent Fries, 67404, Illkirch-Graffenstaden, France.
  • Tocchini-Valentini GP; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Parc d'innovation, 1 Rue Laurent Fries - BP 10142, 67404, Illkirch, France.
  • Beaudet AL; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
  • Bosch F; Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France.
  • Braun RB; Université de Strasbourg, 67404, Illkirch, France.
  • Dobbie MS; CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), 1 Rue Laurent Fries, 67404, Illkirch-Graffenstaden, France.
  • Gao X; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Parc d'innovation, 1 Rue Laurent Fries - BP 10142, 67404, Illkirch, France.
  • Herault Y; Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
  • Moshiri A; Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France.
  • Moore BA; Université de Strasbourg, 67404, Illkirch, France.
  • Kent Lloyd KC; Mouse Biology Program, University of California, One Shields Avenue, Davis, CA, 95616, USA.
  • McKerlie C; Department of Molecular and Human Genetics, Baylor College of Medicine, 7702 Main St, Houston Medical Center, Houston, TX, 77030-4406, USA.
  • Masuya H; The Centre for Phenogenomics, 25 Orde St, Toronto, M5T 3H7, ON, Canada.
  • Tanaka N; The Hospital for Sick Children, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Flicek P; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Parkinson HE; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
  • Sedlacek R; The Centre for Phenogenomics, 25 Orde St, Toronto, M5T 3H7, ON, Canada.
  • Seong JK; The Hospital for Sick Children, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
  • Wang CL; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
  • Moore M; Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.
  • Brown SD; Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Adriano Buzzati-Traverso Campus, Via E. Ramarini 32, Monterotondo Scalo, RM, 00015, Italy.
  • Tschöp MH; The Centre for Phenogenomics, 25 Orde St, Toronto, M5T 3H7, ON, Canada.
  • Wurst W; The Hospital for Sick Children, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Nat Commun ; 9(1): 288, 2018 01 18.
Article em En | MEDLINE | ID: mdl-29348434
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Consumo de Oxigênio / Triglicerídeos / Metabolismo Basal / Glicemia / Peso Corporal / Diabetes Mellitus Tipo 2 / Obesidade Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Consumo de Oxigênio / Triglicerídeos / Metabolismo Basal / Glicemia / Peso Corporal / Diabetes Mellitus Tipo 2 / Obesidade Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article