Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.

Journal article

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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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:

Authors: White, J; Gerdin, A; Karp, N; Ryder, E; Buljan, M

• Publication status: Published
• Journal: Cell
• Volume: 154
• Issue: 2
• Pages: 452-464
• Publication date: 2013-07-01
• DOI: 10.1016/j.cell.2013.06.022
• EISSN: 1097-4172
• ISSN: 0092-8674
• Language: English
• Keywords: Sanger Institute Mouse Genetics Project; Phenotype; Animals; Female; Male; Disease; Genes, Essential; Genetic Techniques; Mice; Disease Models, Animal; Genome-Wide Association Study; Mice, Knockout