The International Mouse Phenotyping Consortium (IMPC): a functional catalogue of the mammalian genome that informs conservation · the IMPC consortium

• Published in: Conservation Genetics
• Main Authors: Muñoz-Fuentes, Violeta, Cacheiro, Pilar, Meehan, Terrence, Aguilar-Pimentel, Juan Antonio, Brown, Steve, Flenniken, Ann, Flicek, Paul, Galli, Antonella, Mashhadi, Hamed Haseli, Hrabě De Angelis, Martin, Kim, Jong Kyoung, Lloyd, K C Kent, McKerlie, Colin, Morgan, Hugh, Murray, Stephen, Nutter, Lauryl, Reilly, Patrick, Seavitt, John, Seong, Je Kyung, Simon, Michelle, Wardle-Jones, Hannah, Mallon, Ann-Marie, Smedley, Damian, Parkinson, Helen
• Other Authors: Queen Mary University of London (QMUL), German Research Center for Environmental Health - Helmholtz Center München (GmbH), European Bioinformatics Institute Hinxton (EMBL-EBI), EMBL Heidelberg, The Wellcome Trust Sanger Institute Cambridge, Institute for Experimental Genetics, GSF - National Research Center for Environment and Health, Medical Research Council Harwell (Mammalian Genetics Unit and Mary Lyon Centre), Medical Research Counc, European Bioinformatics Institute
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2018
• Subjects: Loss-of-function; Endangered species; Cheetah; Non-model species; Panda; Polar bear; Phenotype; Wolf; Essential genes; IMPC; Knockout; Mouse; [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics; [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]; polar bear
• Online Access: https://hal.archives-ouvertes.fr/hal-02361601; https://hal.archives-ouvertes.fr/hal-02361601/document; https://hal.archives-ouvertes.fr/hal-02361601/file/10592_2018_Article_1072.pdf; https://doi.org/10.1007/s10592-018-1072-9

International audience The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and phenotyping a knockout mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species. Here we show, using gorilla genomic data, how genes essential to development in mice can be used to help assess the potentially deleterious impact of gene variants in other species. This type of analyses could be used to select optimal breeders in endangered species to maintain or increase fitness and avoid variants associated to impaired-health phenotypes or loss-of-function mutations in genes of critical importance. We also show, using selected examples from various mammal species, how IMPC data can aid in the identification of candidate genes for studying a condition of interest, deliver information about the mechanisms involved, or support predictions for the function of genes that may play a role in adaptation. With genotyping costs decreasing and the continued improvements of bioinformatics tools, the analyses we demonstrate can be routinely applied.