Large-scale Mouse Deletion Study Published

Among a number of large-scale experiments reported on yeast between 1999-2005 (gene expression, protein-protein interaction, transcription factor binding, etc.), yeast deletion papers by Amy Hin Yan Tong et al. (2001 and 2004) got particular attention, because they connected genes with phenotypes. It is easy to argue that a transcription factor binding measurement is incorrect or irrelevant, but it is too hard to argue against an essential gene.

Now Jacqueline K. White and colleagues at Sanger Institute Mouse Genetics Project make an equally important large-scale knock out study on mice publicly available (h/t: @dgmacarthur). The paper is full of useful insights, among which the finding that novel essential genes are as likely to be related to disease as well-studied ones is the most striking. It will be quite fascinating, when this project gets to cover the entire set of genes in mouse. The paper is open-access and the mice are getting proper care in accordance with the UK Home Of?ce regulations. So, you have very little to complain about.

Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes

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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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