Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium.

Autor: Meehan TF; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Conte N; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., West DB; Children's Hospital Oakland Research Institute, Oakland, California, USA., Jacobsen JO; William Harvey Research Institute, Queen Mary University of London, London, UK., Mason J; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Warren J; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Chen CK; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Tudose I; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Relac M; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Matthews P; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Karp N; The Wellcome Trust Sanger Institute, Hinxton, UK., Santos L; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Fiegel T; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Ring N; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Westerberg H; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Greenaway S; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Sneddon D; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Morgan H; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Codner GF; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Stewart ME; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Brown J; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Horner N; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Haendel M; Department of Medical Informatics and Clinical Epidemiology and OHSU Library, Oregon Health &Science University, Portland, Oregon, USA., Washington N; Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA., Mungall CJ; Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA., Reynolds CL; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Gallegos J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Gailus-Durner V; Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Neuherberg, Germany., Sorg T; CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch-Graffenstaden, France.; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France., Pavlovic G; CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch-Graffenstaden, France.; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France., Bower LR; Mouse Biology Program, University of California, Davis, Davis, California, USA., Moore M; IMPC, San Anselmo, California, USA., Morse I; Charles River Laboratories, Wilmington, Massachusetts, USA., Gao X; SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China., Tocchini-Valentini GP; Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo, Italy., Obata Y; RIKEN BioResource Center, Tsukuba, Japan., Cho SY; Korea Mouse Phenotyping Center, Seoul, Republic of Korea.; National Cancer Center, Goyang, Republic of Korea., Seong JK; Korea Mouse Phenotyping Center, Seoul, Republic of Korea.; Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea., Seavitt J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Beaudet AL; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Dickinson ME; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Herault Y; CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch-Graffenstaden, France.; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France., Wurst W; Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Neuherberg, Germany., de Angelis MH; Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Neuherberg, Germany., Lloyd KCK; Mouse Biology Program, University of California, Davis, Davis, California, USA., Flenniken AM; Centre for Phenogenomics, Toronto, Ontario, Canada., Nutter LMJ; Centre for Phenogenomics, Toronto, Ontario, Canada., Newbigging S; Centre for Phenogenomics, Toronto, Ontario, Canada., McKerlie C; Centre for Phenogenomics, Toronto, Ontario, Canada., Justice MJ; Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada., Murray SA; Jackson Laboratory, Bar Harbor, Maine, USA., Svenson KL; Jackson Laboratory, Bar Harbor, Maine, USA., Braun RE; Jackson Laboratory, Bar Harbor, Maine, USA., White JK; The Wellcome Trust Sanger Institute, Hinxton, UK., Bradley A; The Wellcome Trust Sanger Institute, Hinxton, UK., Flicek P; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Wells S; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Skarnes WC; The Wellcome Trust Sanger Institute, Hinxton, UK., Adams DJ; The Wellcome Trust Sanger Institute, Hinxton, UK., Parkinson H; European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK., Mallon AM; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Brown SDM; Medical Research Council Harwell, Mammalian Genetics Unit and Mary Lyon Centre, Harwell, UK., Smedley D; William Harvey Research Institute, Queen Mary University of London, London, UK.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2017 Aug; Vol. 49 (8), pp. 1231-1238. Date of Electronic Publication: 2017 Jun 26.
DOI: 10.1038/ng.3901
Abstrakt: Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.
Databáze: MEDLINE
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