High-throughput discovery of novel developmental phenotypes.
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| 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. |
| Year of Publication | 2016
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| Journal | Nature
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| Volume | 537
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| Issue | 7621
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| Pages | 508-514
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| Date Published | 2016 Sep 22
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| ISSN | 1476-4687
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| DOI | 10.1038/nature19356
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| PubMed ID | 27626380
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| PubMed Central ID | PMC5295821
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| Grant list | U54 HG006332 / HG / NHGRI NIH HHS / United States
U54 HG006364 / HG / NHGRI NIH HHS / United States
U42 OD011174 / OD / NIH HHS / United States
U54 HG006348 / HG / NHGRI NIH HHS / United States
U54 HG006370 / HG / NHGRI NIH HHS / United States
U42 OD011175 / OD / NIH HHS / United States
U42 OD011185 / OD / NIH HHS / United States
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