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Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.
Swan, Anna L; Schütt, Christine; Rozman, Jan; Del Mar Muñiz Moreno, Maria; Brandmaier, Stefan; Simon, Michelle; Leuchtenberger, Stefanie; Griffiths, Mark; Brommage, Robert; Keskivali-Bond, Piia; Grallert, Harald; Werner, Thomas; Teperino, Raffaele; Becker, Lore; Miller, Gregor; Moshiri, Ala; Seavitt, John R; Cissell, Derek D; Meehan, Terrence F; Acar, Elif F; Lelliott, Christopher J; Flenniken, Ann M; Champy, Marie-France; Sorg, Tania; Ayadi, Abdel; Braun, Robert E; Cater, Heather; Dickinson, Mary E; Flicek, Paul; Gallegos, Juan; Ghirardello, Elena J; Heaney, Jason D; Jacquot, Sylvie; Lally, Connor; Logan, John G; Teboul, Lydia; Mason, Jeremy; Spielmann, Nadine; McKerlie, Colin; Murray, Stephen A; Nutter, Lauryl M J; Odfalk, Kristian F; Parkinson, Helen; Prochazka, Jan; Reynolds, Corey L; Selloum, Mohammed; Spoutil, Frantisek; Svenson, Karen L; Vales, Taylor S; Wells, Sara E.
Affiliation
  • Swan AL; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom.
  • Schütt C; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Rozman J; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Del Mar Muñiz Moreno M; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • Brandmaier S; Czech Center for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences,Vestec, Czech Republic.
  • Simon M; Université de Strasbourg, CNRS, INSERM, IGBMC, Illkirch, France.
  • Leuchtenberger S; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • Griffiths M; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Brommage R; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom.
  • Keskivali-Bond P; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Grallert H; Mouse Informatics Group, Wellcome Sanger Institute, Hinxton, United Kingdom.
  • Werner T; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Teperino R; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom.
  • Becker L; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • Miller G; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Moshiri A; Internal Medicine Nephrology and Center for Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America.
  • Seavitt JR; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • Cissell DD; Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Meehan TF; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Acar EF; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Lelliott CJ; University of California-Davis School of Medicine, Sacramento, California, United States of America.
  • Flenniken AM; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
  • Champy MF; Department of Surgical & Radiological Sciences, University of California, Davis, California, United States of America.
  • Sorg T; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
  • Ayadi A; The Center for Phenogenomics, Toronto, Ontario, Canada.
  • Braun RE; The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
  • Cater H; Department of Statistics, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Dickinson ME; Mouse Pipelines, Wellcome Sanger Institute, Hinxton, United Kingdom.
  • Flicek P; The Center for Phenogenomics, Toronto, Ontario, Canada.
  • Gallegos J; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
  • Ghirardello EJ; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France.
  • Heaney JD; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France.
  • Jacquot S; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France.
  • Lally C; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America.
  • Logan JG; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom.
  • Teboul L; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
  • Mason J; Departments of Molecular Physiology & Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston,Texas, United States of America.
  • Spielmann N; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
  • McKerlie C; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
  • Murray SA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, United States of America.
  • Nutter LMJ; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London, United Kingdom.
  • Odfalk KF; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
  • Parkinson H; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, United States of America.
  • Prochazka J; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France.
  • Reynolds CL; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom.
  • Selloum M; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London, United Kingdom.
  • Spoutil F; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom.
  • Svenson KL; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
  • Vales TS; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.
  • Wells SE; The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
PLoS Genet ; 16(12): e1009190, 2020 12.
Article in En | MEDLINE | ID: mdl-33370286
ABSTRACT
The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteoblasts / Osteoclasts / Osteoporosis / Bone Density / Gene Expression Regulation Limits: Animals Language: En Journal: PLoS Genet Journal subject: GENETICA Year: 2020 Document type: Article Affiliation country: United kingdom
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteoblasts / Osteoclasts / Osteoporosis / Bone Density / Gene Expression Regulation Limits: Animals Language: En Journal: PLoS Genet Journal subject: GENETICA Year: 2020 Document type: Article Affiliation country: United kingdom