High-throughput discovery of novel developmental phenotypes.

Abstract:

:Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.

journal_name

Nature

journal_title

Nature

authors

Dickinson ME,Flenniken AM,Ji X,Teboul L,Wong MD,White JK,Meehan TF,Weninger WJ,Westerberg H,Adissu H,Baker CN,Bower L,Brown JM,Caddle LB,Chiani F,Clary D,Cleak J,Daly MJ,Denegre JM,Doe B,Dolan ME,Edie SM,Fuchs

doi

10.1038/nature19356

subject

Has Abstract

pub_date

2016-09-22 00:00:00

pages

508-514

issue

7621

eissn

0028-0836

issn

1476-4687

pii

nature19356

journal_volume

537

pub_type

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