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Publication
High-throughput discovery of novel developmental phenotypes.
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
H, Gailus-Durner V, Galli A, Gambadoro A, Gallegos J, Guo S, Horner NR, Hsu CW,
Johnson SJ, Kalaga S, Keith LC, Lanoue L, Lawson TN, Lek M, Mark M, Marschall S,
Mason J, McElwee ML, Newbigging S, Nutter LM, Peterson KA, Ramirez-Solis R,
Rowland DJ, Ryder E, Samocha KE
Submitted By Submitted Externally on 5/1/2017
Status Published
Journal Nature
Year 2016
Date Published 9/1/2016
Volume : Pages 537 : 508 - 514
PubMed Reference 27626380
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.




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