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Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP:

Original publication

DOI

10.1016/j.cell.2013.06.022

Type

Journal article

Journal

Cell

Publication Date

18/07/2013

Volume

154

Pages

452 - 464

Keywords

Animals, Disease, Disease Models, Animal, Female, Genes, Essential, Genetic Techniques, Genome-Wide Association Study, Male, Mice, Mice, Knockout, Phenotype