Title

High-throughput discovery of novel developmental phenotypes.

Authors

Mary E Dickinson
Ann M Flenniken
Xiao Ji
Lydia Teboul
Michael D Wong
Jacqueline K White
Terrence F Meehan
Wolfgang J Weninger
Henrik Westerberg
Hibret Adissu
Candice N Baker, The Jackson LaboratoryFollow
Lynette Bower
James M Brown
L Brianna Caddle, The Jackson LaboratoryFollow
Francesco Chiani
Dave Clary
James Cleak
Mark J Daly
James M. Denegre, The Jackson LaboratoryFollow
Brendan Doe
Mary E. Dolan, The Jackson LaboratoryFollow
Sarah M Edie, The Jackson LaboratoryFollow
Helmut Fuchs
Valerie Gailus-Durner
Antonella Galli
Alessia Gambadoro
Juan Gallegos
Shiying Guo
Neil R Horner
Chih-Wei Hsu
Sara J Johnson
Sowmya Kalaga
Lance C Keith
Louise Lanoue
Thomas N Lawson
Monkol Lek
Manuel Mark
Susan Marschall
Jeremy Mason
Melissa L McElwee
Susan Newbigging
Lauryl M J Nutter
Kevin A Peterson, The Jackson LaboratoryFollow
Ramiro Ramirez-Solis
Douglas J Rowland
Edward Ryder
Kaitlin E Samocha
John R Seavitt
Mohammed Selloum
Zsombor Szoke-Kovacs
Masaru Tamura
Amanda G Trainor
Ilinca Tudose
Shigeharu Wakana
Jonathan Warren
Olivia Wendling
David B West
Leeyean Wong
Atsushi Yoshiki
Daniel G MacArthur
Glauco P Tocchini-Valentini
Xiang Gao
Paul Flicek
Allan Bradley
William C Skarnes
Monica J Justice
Helen E Parkinson
Mark Moore
Sara Wells
Robert E Braun, The Jackson LaboratoryFollow
Karen L Svenson, The Jackson LaboratoryFollow
Martin Hrabe de Angelis
Yann Herault
Tim Mohun
Ann-Marie Mallon
R Mark Henkelman
Steve D M Brown
David J Adams
K C Kent Lloyd
Colin McKerlie
Arthur L Beaudet
Maja Bućan
Stephen A Murray, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

9-14-2016

JAX Source

Nature 2016 Sep 14; 537(7621):508-514

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.