Muñoz-Fuentes Violeta, Cacheiro Pilar, Meehan Terrence F, Aguilar-Pimentel Juan Antonio, Brown Steve D M, Flenniken Ann M, Flicek Paul, Galli Antonella, Mashhadi Hamed Haseli, Hrabě de Angelis Martin, Kim Jong Kyoung, Lloyd K C Kent, McKerlie Colin, Morgan Hugh, Murray Stephen A, Nutter Lauryl M J, Reilly Patrick T, Seavitt John R, Seong Je Kyung, Simon Michelle, Wardle-Jones Hannah, Mallon Ann-Marie, Smedley Damian, Parkinson Helen E
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD UK.
2Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ UK.
Conserv Genet. 2018;19(4):995-1005. doi: 10.1007/s10592-018-1072-9. Epub 2018 May 19.
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.
国际小鼠表型分析联盟（IMPC）正在通过为每个蛋白质编码基因培育一个基因敲除小鼠品系并对其进行表型分析，来构建一个哺乳动物基因功能目录。到目前为止，IMPC已经培育并鉴定了5186个突变品系。已发现三分之一的品系无法存活，迄今为止已鉴定出300多种新的人类疾病小鼠模型。虽然目前的生物信息学工作重点是转化研究结果以更好地理解人类疾病过程，但IMPC的数据也有助于理解其他物种的基因功能和过程。在此，我们利用大猩猩基因组数据展示了如何利用小鼠发育所必需的基因来帮助评估其他物种中基因变异的潜在有害影响。这类分析可用于选择濒危物种的最佳繁殖个体，以维持或提高适应性，并避免与健康受损表型或关键基因功能丧失突变相关的变异。我们还利用来自各种哺乳动物物种的选定实例展示了IMPC数据如何有助于鉴定用于研究感兴趣病症的候选基因、提供有关所涉及机制的信息，或支持对可能在适应性中起作用的基因功能的预测。随着基因分型成本的降低以及生物信息学工具的不断改进，我们所展示的分析可以常规应用。
