title: Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.
abstract: 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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Gerdin
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Karp
authors.forename: Ed
authors.initials: E
authors.lastname: Ryder
authors.forename: Marija
authors.initials: M
authors.lastname: Buljan
authors.forename: James N
authors.initials: JN
authors.lastname: Bussell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Salisbury
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Ingham
authors.forename: Christine
authors.initials: C
authors.lastname: Podrini
authors.forename: Richard
authors.initials: R
authors.lastname: Houghton
authors.forename: Jeanne
authors.initials: J
authors.lastname: Estabel
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Bottomley
authors.forename: David G
authors.initials: DG
authors.lastname: Melvin
authors.forename: David
authors.initials: D
authors.lastname: Sunter
authors.forename: Niels C
authors.initials: NC
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: Tannahill
authors.forename: Darren W
authors.initials: DW
authors.lastname: Logan
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Macarthur
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: Vinit B
authors.initials: VB
authors.lastname: Mahajan
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Tsang
authors.forename: Ian
authors.initials: I
authors.lastname: Smyth
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
authors.forename: William C
authors.initials: WC
authors.lastname: Skarnes
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Ramiro
authors.initials: R
authors.lastname: Ramirez-Solis
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D000818:Animals; D004194:Disease / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020043:Genes, Essential; D005821:Genetic Techniques; D055106:Genome-Wide Association Study; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype