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

Jacqueline K White; Anna-Karin Gerdin; Natasha A Karp; Ed Ryder; Marija Buljan; James N Bussell; Jennifer Salisbury; Simon Clare; Neil J Ingham; Christine Podrini; Richard Houghton; Jeanne Estabel; Joanna R Bottomley; David G Melvin; David Sunter; Niels C Adams; Sanger Institute Mouse Genetics Project; David Tannahill; Darren W Logan; Daniel G Macarthur; Jonathan Flint; Vinit B Mahajan; Stephen H Tsang; Ian Smyth; Fiona M Watt; William C Skarnes; Gordon Dougan; David J Adams; Ramiro Ramirez-Solis; Allan Bradley; Karen P Steel

doi:10.1016/j.cell.2013.06.022

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

Jacqueline K White, Anna-Karin Gerdin, Natasha A Karp, Ed Ryder, Marija Buljan, James N Bussell, Jennifer Salisbury, Simon Clare, Neil J Ingham, Christine Podrini, Richard Houghton, Jeanne Estabel, Joanna R Bottomley, David G Melvin, David Sunter, Niels C Adams, Sanger Institute Mouse Genetics Project, David Tannahill, Darren W Logan, Daniel G MacarthurJonathan Flint, Vinit B Mahajan, Stephen H Tsang, Ian Smyth, Fiona M Watt, William C Skarnes, Gordon Dougan, David J Adams, Ramiro Ramirez-Solis, Allan Bradley, Karen P Steel

Wellcome Sanger Institute

Research output: Contribution to journal › Article › peer-review

415 Citations (Scopus)

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 We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of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

Original language	English
Pages (from-to)	452-464
Number of pages	13
Journal	Cell
Volume	154
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2013.06.022
Publication status	Published - 18 Jul 2013

Keywords

DUPLICATE GENES
INTELLECTUAL DISABILITY
TRANSMEMBRANE PROTEINS
DEFICIENCY CAUSES
MOUSE
RESOURCE
EXPRESSION
MUTATIONS
GENETICS
ROBUSTNESS

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10.1016/j.cell.2013.06.022

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White, J. K., Gerdin, A.-K., Karp, N. A., Ryder, E., Buljan, M., Bussell, J. N., Salisbury, J., Clare, S., Ingham, N. J., Podrini, C., Houghton, R., Estabel, J., Bottomley, J. R., Melvin, D. G., Sunter, D., Adams, N. C., Sanger Institute Mouse Genetics Project, Tannahill, D., Logan, D. W., ... Steel, K. P. (2013). Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes. Cell, 154(2), 452-464. https://doi.org/10.1016/j.cell.2013.06.022

@article{c880eddc8bd34d649be84af23ae029a6,

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.",

keywords = "DUPLICATE GENES, INTELLECTUAL DISABILITY, TRANSMEMBRANE PROTEINS, DEFICIENCY CAUSES, MOUSE, RESOURCE, EXPRESSION, MUTATIONS, GENETICS, ROBUSTNESS",

author = "White, {Jacqueline K} and Anna-Karin Gerdin and Karp, {Natasha A} and Ed Ryder and Marija Buljan and Bussell, {James N} and Jennifer Salisbury and Simon Clare and Ingham, {Neil J} and Christine Podrini and Richard Houghton and Jeanne Estabel and Bottomley, {Joanna R} and Melvin, {David G} and David Sunter and Adams, {Niels C} and {Sanger Institute Mouse Genetics Project} and David Tannahill and Logan, {Darren W} and Macarthur, {Daniel G} and Jonathan Flint and Mahajan, {Vinit B} and Tsang, {Stephen H} and Ian Smyth and Watt, {Fiona M} and Skarnes, {William C} and Gordon Dougan and Adams, {David J} and Ramiro Ramirez-Solis and Allan Bradley and Steel, {Karen P}",

year = "2013",

month = jul,

day = "18",

doi = "10.1016/j.cell.2013.06.022",

language = "English",

volume = "154",

pages = "452--464",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "2",

}

White, JK, Gerdin, A-K, 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, 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 2013, 'Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes', Cell, vol. 154, no. 2, pp. 452-464. https://doi.org/10.1016/j.cell.2013.06.022

TY - JOUR

T1 - Genome-wide Generation and Systematic Phenotyping of Knockout Mice Reveals New Roles for Many Genes

AU - White, Jacqueline K

AU - Gerdin, Anna-Karin

AU - Karp, Natasha A

AU - Ryder, Ed

AU - Buljan, Marija

AU - Bussell, James N

AU - Salisbury, Jennifer

AU - Clare, Simon

AU - Ingham, Neil J

AU - Podrini, Christine

AU - Houghton, Richard

AU - Estabel, Jeanne

AU - Bottomley, Joanna R

AU - Melvin, David G

AU - Sunter, David

AU - Adams, Niels C

AU - Sanger Institute Mouse Genetics Project

AU - Tannahill, David

AU - Logan, Darren W

AU - Macarthur, Daniel G

AU - Flint, Jonathan

AU - Mahajan, Vinit B

AU - Tsang, Stephen H

AU - Smyth, Ian

AU - Watt, Fiona M

AU - Skarnes, William C

AU - Dougan, Gordon

AU - Adams, David J

AU - Ramirez-Solis, Ramiro

AU - Bradley, Allan

AU - Steel, Karen P

PY - 2013/7/18

Y1 - 2013/7/18

N2 - 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.

AB - 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.

KW - DUPLICATE GENES

KW - INTELLECTUAL DISABILITY

KW - TRANSMEMBRANE PROTEINS

KW - DEFICIENCY CAUSES

KW - MOUSE

KW - RESOURCE

KW - EXPRESSION

KW - MUTATIONS

KW - GENETICS

KW - ROBUSTNESS

U2 - 10.1016/j.cell.2013.06.022

DO - 10.1016/j.cell.2013.06.022

M3 - Article

C2 - 23870131

SN - 0092-8674

VL - 154

SP - 452

EP - 464

JO - Cell

JF - Cell

IS - 2

ER -

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

Abstract

Keywords

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