Affiliation: | 1.European Molecular Biology Laboratory,European Bioinformatics Institute (EMBL-EBI),Cambridge,UK;2.Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry,Queen Mary University of London,London,UK;3.German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München,German Research Center for Environmental Health,Neuherberg,Germany;4.Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre),Harwell,UK;5.The Centre for Phenogenomics,Toronto,Canada;6.Mount Sinai Hospital,Toronto,Canada;7.Wellcome Trust Sanger Institute,Cambridge,UK;8.German Center for Diabetes Research (DZD),Neuherberg,Germany;9.School of Life Science Weihenstephan,Technische Universit?t München,Freising,Germany;10.Department of New Biology,DGIST,Daegu,Republic of Korea;11.Mouse Biology Program,University of California,Davis,USA;12.The Hospital for Sick Children,Toronto,Canada;13.The Jackson Laboratory,Bar Harbor,USA;14.PHENOMIN-iCS,Illkirch Cedex,France;15.Department of Molecular and Human Genetics,Baylor College of Medicine,Houston,USA;16.Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Interdisciplinary Program for Bioinformatics and Program for Cancer Biology,Seoul National University,Seoul,Republic of Korea |
Abstract: | 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. |