Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium

Terrence F. Meehan; Nathalie Conte; David B. West; Julius O. Jacobsen; Jeremy Mason; Jonathan Warren; Chao Kung Chen; Ilinca Tudose; Mike Relac; Peter Matthews; Natasha Karp; Luis Santos; Tanja Fiegel; Natalie Ring; Henrik Westerberg; Simon Greenaway; Duncan Sneddon; Hugh Morgan; Gemma F. Codner; Michelle E. Stewart; James Brown; Neil Horner; Melissa Haendel; Nicole Washington; Christopher J. Mungall; Corey L. Reynolds; Juan Gallegos; Valerie Gailus-Durner; Tania Sorg; Guillaume Pavlovic; Lynette R. Bower; Mark Moore; Iva Morse; Xiang Gao; Glauco P. Tocchini-Valentini; Yuichi Obata; Soo Young Cho; Je Kyung Seong; John Seavitt; Arthur L. Beaudet; Mary E. Dickinson; Yann Herault; Wolfgang Wurst; Martin Hrabe De Angelis; K. C. Kent Lloyd; Ann M. Flenniken; Lauryl M.J. Nutter; Susan Newbigging; Colin McKerlie; Monica J. Justice; Stephen A. Murray; Karen L. Svenson; Robert E. Braun; Jacqueline K. White; Allan Bradley; Paul Flicek; Sara Wells; William C. Skarnes; David J. Adams; Helen Parkinson; Ann Marie Mallon; Steve D.M. Brown; Damian Smedley

doi:10.1038/ng.3901

Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium

Terrence F. Meehan, Nathalie Conte, David B. West, Julius O. Jacobsen, Jeremy Mason, Jonathan Warren, Chao Kung Chen, Ilinca Tudose, Mike Relac, Peter Matthews, Natasha Karp, Luis Santos, Tanja Fiegel, Natalie Ring, Henrik Westerberg, Simon Greenaway, Duncan Sneddon, Hugh Morgan, Gemma F. Codner, Michelle E. StewartJames Brown, Neil Horner, Melissa Haendel, Nicole Washington, Christopher J. Mungall, Corey L. Reynolds, Juan Gallegos, Valerie Gailus-Durner, Tania Sorg, Guillaume Pavlovic, Lynette R. Bower, Mark Moore, Iva Morse, Xiang Gao, Glauco P. Tocchini-Valentini, Yuichi Obata, Soo Young Cho, Je Kyung Seong, John Seavitt, Arthur L. Beaudet, Mary E. Dickinson, Yann Herault, Wolfgang Wurst, Martin Hrabe De Angelis, K. C. Kent Lloyd, Ann M. Flenniken, Lauryl M.J. Nutter, Susan Newbigging, Colin McKerlie, Monica J. Justice, Stephen A. Murray, Karen L. Svenson, Robert E. Braun, Jacqueline K. White, Allan Bradley, Paul Flicek, Sara Wells, William C. Skarnes, David J. Adams, Helen Parkinson, Ann Marie Mallon, Steve D.M. Brown, Damian Smedley

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Abstract

Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.

Original language	English (US)
Pages (from-to)	1231-1238
Number of pages	8
Journal	Nature genetics
Volume	49
Issue number	8
DOIs	https://doi.org/10.1038/ng.3901
State	Published - Aug 1 2017

ASJC Scopus subject areas

Genetics

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Meehan, T. F., Conte, N., West, D. B., Jacobsen, J. O., Mason, J., Warren, J., Chen, C. K., Tudose, I., Relac, M., Matthews, P., Karp, N., Santos, L., Fiegel, T., Ring, N., Westerberg, H., Greenaway, S., Sneddon, D., Morgan, H., Codner, G. F., ... Smedley, D. (2017). Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium. Nature genetics, 49(8), 1231-1238. https://doi.org/10.1038/ng.3901

Meehan, TF, Conte, N, West, DB, Jacobsen, JO, Mason, J, Warren, J, Chen, CK, Tudose, I, Relac, M, Matthews, P, Karp, N, Santos, L, Fiegel, T, Ring, N, Westerberg, H, Greenaway, S, Sneddon, D, Morgan, H, Codner, GF, Stewart, ME, Brown, J, Horner, N, Haendel, M, Washington, N, Mungall, CJ, Reynolds, CL, Gallegos, J, Gailus-Durner, V, Sorg, T, Pavlovic, G, Bower, LR, Moore, M, Morse, I, Gao, X, Tocchini-Valentini, GP, Obata, Y, Cho, SY, Seong, JK, Seavitt, J, Beaudet, AL, Dickinson, ME, Herault, Y, Wurst, W, De Angelis, MH, Kent Lloyd, KC, Flenniken, AM, Nutter, LMJ, Newbigging, S, McKerlie, C, Justice, MJ, Murray, SA, Svenson, KL, Braun, RE, White, JK, Bradley, A, Flicek, P, Wells, S, Skarnes, WC, Adams, DJ, Parkinson, H, Mallon, AM, Brown, SDM & Smedley, D 2017, 'Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium', Nature genetics, vol. 49, no. 8, pp. 1231-1238. https://doi.org/10.1038/ng.3901

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title = "Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium",

abstract = "Although next-generation sequencing has revolutionized the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by a lack of knowledge of the functions and pathobiological mechanisms of most genes. To address this challenge, the International Mouse Phenotyping Consortium is creating a genome- and phenome-wide catalog of gene function by characterizing new knockout-mouse strains across diverse biological systems through a broad set of standardized phenotyping tests. All mice will be readily available to the biomedical community. Analyzing the first 3,328 genes identified models for 360 diseases, including the first models, to our knowledge, for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations were novel, providing functional evidence for 1,092 genes and candidates in genetically uncharacterized diseases including arrhythmogenic right ventricular dysplasia 3. Finally, we describe our role in variant functional validation with The 100,000 Genomes Project and others.",

author = "Meehan, {Terrence F.} and Nathalie Conte and West, {David B.} and Jacobsen, {Julius O.} and Jeremy Mason and Jonathan Warren and Chen, {Chao Kung} and Ilinca Tudose and Mike Relac and Peter Matthews and Natasha Karp and Luis Santos and Tanja Fiegel and Natalie Ring and Henrik Westerberg and Simon Greenaway and Duncan Sneddon and Hugh Morgan and Codner, {Gemma F.} and Stewart, {Michelle E.} and James Brown and Neil Horner and Melissa Haendel and Nicole Washington and Mungall, {Christopher J.} and Reynolds, {Corey L.} and Juan Gallegos and Valerie Gailus-Durner and Tania Sorg and Guillaume Pavlovic and Bower, {Lynette R.} and Mark Moore and Iva Morse and Xiang Gao and Tocchini-Valentini, {Glauco P.} and Yuichi Obata and Cho, {Soo Young} and Seong, {Je Kyung} and John Seavitt and Beaudet, {Arthur L.} and Dickinson, {Mary E.} and Yann Herault and Wolfgang Wurst and {De Angelis}, {Martin Hrabe} and {Kent Lloyd}, {K. C.} and Flenniken, {Ann M.} and Nutter, {Lauryl M.J.} and Susan Newbigging and Colin McKerlie and Justice, {Monica J.} and Murray, {Stephen A.} and Svenson, {Karen L.} and Braun, {Robert E.} and White, {Jacqueline K.} and Allan Bradley and Paul Flicek and Sara Wells and Skarnes, {William C.} and Adams, {David J.} and Helen Parkinson and Mallon, {Ann Marie} and Brown, {Steve D.M.} and Damian Smedley",

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AU - Conte, Nathalie

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AU - Jacobsen, Julius O.

AU - Mason, Jeremy

AU - Warren, Jonathan

AU - Chen, Chao Kung

AU - Tudose, Ilinca

AU - Relac, Mike

AU - Matthews, Peter

AU - Karp, Natasha

AU - Santos, Luis

AU - Fiegel, Tanja

AU - Ring, Natalie

AU - Westerberg, Henrik

AU - Greenaway, Simon

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AU - Morgan, Hugh

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AU - Brown, James

AU - Horner, Neil

AU - Haendel, Melissa

AU - Washington, Nicole

AU - Mungall, Christopher J.

AU - Reynolds, Corey L.

AU - Gallegos, Juan

AU - Gailus-Durner, Valerie

AU - Sorg, Tania

AU - Pavlovic, Guillaume

AU - Bower, Lynette R.

AU - Moore, Mark

AU - Morse, Iva

AU - Gao, Xiang

AU - Tocchini-Valentini, Glauco P.

AU - Obata, Yuichi

AU - Cho, Soo Young

AU - Seong, Je Kyung

AU - Seavitt, John

AU - Beaudet, Arthur L.

AU - Dickinson, Mary E.

AU - Herault, Yann

AU - Wurst, Wolfgang

AU - De Angelis, Martin Hrabe

AU - Kent Lloyd, K. C.

AU - Flenniken, Ann M.

AU - Nutter, Lauryl M.J.

AU - Newbigging, Susan

AU - McKerlie, Colin

AU - Justice, Monica J.

AU - Murray, Stephen A.

AU - Svenson, Karen L.

AU - Braun, Robert E.

AU - White, Jacqueline K.

AU - Bradley, Allan

AU - Flicek, Paul

AU - Wells, Sara

AU - Skarnes, William C.

AU - Adams, David J.

AU - Parkinson, Helen

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AU - Brown, Steve D.M.

AU - Smedley, Damian

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Disease model discovery from 3,328 gene knockouts by the International Mouse Phenotyping Consortium

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