High-throughput discovery of novel developmental phenotypes.
Document Type
Article
Publication Date
9-14-2016
JAX Source
Nature 2016 Sep 14; 537(7621):508-514
Volume
537
Issue
7621
First Page
508
Last Page
514
ISSN
1476-4687
PMID
27626380
Grant
U42 0D011185, U54 HG006332
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. Nature 2016 Sep 14; 537(7621):508-514.
Recommended Citation
Dickinson M,
Flenniken A,
Ji X,
Teboul L,
Wong M,
White J,
Meehan T,
Weninger W,
Westerberg H,
Adissu H,
Baker C,
Bower L,
Brown J,
Caddle L,
Chiani F,
Clary D,
Cleak J,
Daly M,
Denegre JM,
Doe B,
Dolan ME,
Edie S,
Fuchs H,
Gailus-Durner V,
Galli A,
Gambadoro A,
Gallegos J,
Guo S,
Horner N,
Hsu C,
Johnson S,
Kalaga S,
Keith L,
Lanoue L,
Lawson T,
Lek M,
Mark M,
Marschall S,
Mason J,
McElwee M,
Newbigging S,
Nutter L,
Peterson K,
Ramirez-Solis R,
Rowland D,
Ryder E,
Samocha K,
Seavitt J,
Selloum M,
Szoke-Kovacs Z,
Tamura M,
Trainor A,
Tudose I,
Wakana S,
Warren J,
Wendling O,
West D,
Wong L,
Yoshiki A,
MacArthur D,
Tocchini-Valentini G,
Gao X,
Flicek P,
Bradley A,
Skarnes W,
Justice M,
Parkinson H,
Moore M,
Wells S,
Braun R,
Svenson K,
de Angelis M,
Herault Y,
Mohun T,
Mallon A,
Henkelman R,
Brown S,
Adams D,
Lloyd K,
McKerlie C,
Beaudet A,
Bućan M,
Murray S.
High-throughput discovery of novel developmental phenotypes. Nature 2016 Sep 14; 537(7621):508-514