Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.
White JK., Gerdin AK., Karp NA., Ryder E., Buljan M., Bussell JN., Salisbury J., Clare S., Ingham NJ., Podrini C., Houghton R., Estabel J., Bottomley JR., Melvin DG., Sunter D., Adams NC., Sanger Institute Mouse Genetics Project None., Tannahill D., Logan DW., Macarthur DG., Flint J., Mahajan VB., Tsang SH., Smyth I., Watt FM., Skarnes WC., Dougan G., Adams DJ., Ramirez-Solis R., Bradley A., Steel KP.
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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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: