High-throughput discovery of novel developmental phenotypes

The International Mouse Phenotyping Consortium

Research output: Contribution to journalArticle

301 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)508-514
Number of pages7
JournalNature
Volume537
Issue number7621
DOIs
StatePublished - Sep 14 2016

ASJC Scopus subject areas

  • Medicine(all)
  • General

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    The International Mouse Phenotyping Consortium (2016). High-throughput discovery of novel developmental phenotypes. Nature, 537(7621), 508-514. https://doi.org/10.1038/nature19356