Title

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

Document Type

Article

Publication Date

8-2017

JAX Source

Nat Genet 2017 Aug; 49(8):1231-1238

PMID

28650483

DOI

https://doi.org/10.1038/ng.3901

Grant

OD011185, HG006332

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. Nat Genet 2017 Aug; 49(8):1231-1238.