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

Terrence F. Meehan, Nathalie Conte, David B. West, Julius O. Jacobsen, Jeremy Mason, Jonathan Warren, Chao Kung Chen, Ilinca Tudose, Mike Relac, Peter Matthews, Natasha Karp, Luis Santos, Tanja Fiegel, Natalie Ring, Henrik Westerberg, Simon Greenaway, Duncan Sneddon, Hugh Morgan, Gemma F. Codner, Michelle E. StewartJames Brown, Neil Horner, Melissa Haendel, Nicole Washington, Christopher J. Mungall, Corey L. Reynolds, Juan Gallegos, Valerie Gailus-Durner, Tania Sorg, Guillaume Pavlovic, Lynette R. Bower, Mark Moore, Iva Morse, Xiang Gao, Glauco P. Tocchini-Valentini, Yuichi Obata, Soo Young Cho, Je Kyung Seong, John Seavitt, Arthur L. Beaudet, Mary E. Dickinson, Yann Herault, Wolfgang Wurst, Martin Hrabe De Angelis, K. C. Kent Lloyd, Ann M. Flenniken, Lauryl M.J. Nutter, Susan Newbigging, Colin McKerlie, Monica J. Justice, Stephen A. Murray, Karen L. Svenson, Robert E. Braun, Jacqueline K. White, Allan Bradley, Paul Flicek, Sara Wells, William C. Skarnes, David J. Adams, Helen Parkinson, Ann Marie Mallon, Steve D.M. Brown, Damian Smedley

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1231-1238
Number of pages8
JournalNature genetics
Volume49
Issue number8
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Genetics

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    Meehan, T. F., Conte, N., West, D. B., Jacobsen, J. O., Mason, J., Warren, J., Chen, C. K., Tudose, I., Relac, M., Matthews, P., Karp, N., Santos, L., Fiegel, T., Ring, N., Westerberg, H., Greenaway, S., Sneddon, D., Morgan, H., Codner, G. F., ... Smedley, D. (2017). Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium. Nature genetics, 49(8), 1231-1238. https://doi.org/10.1038/ng.3901