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

被引：179

作者：

Meehan, Terrence F. ^{[1
]}

Conte, Nathalie ^{[1
]}

West, David B. ^{[2
]}

Jacobsen, Julius O. ^{[3
]}

Mason, Jeremy ^{[1
]}

Warren, Jonathan ^{[1
]}

Chen, Chao-Kung ^{[1
]}

Tudose, Ilinca ^{[1
]}

Relac, Mike ^{[1
]}

Matthews, Peter ^{[1
]}

Karp, Natasha ^{[4
]}

Santos, Luis ^{[5
,6
]}

Fiegel, Tanja ^{[5
,6
]}

Ring, Natalie ^{[5
,6
]}

Westerberg, Henrik ^{[5
,6
]}

Greenaway, Simon ^{[5
,6
]}

Sneddon, Duncan ^{[5
,6
]}

Morgan, Hugh ^{[5
,6
]}

Codner, Gemma F. ^{[5
,6
]}

Stewart, Michelle E. ^{[5
,6
]}

Brown, James ^{[5
,6
]}

Horner, Neil ^{[5
,6
]}

Haendel, Melissa ^{[7
,8
,9
]}

Washington, Nicole ^{[10
]}

Mungall, Christopher J. ^{[10
]}

Reynolds, Corey L. ^{[11
]}

Gallegos, Juan ^{[11
]}

Gailus-Durner, Valerie ^{[12
]}

Sorg, Tania ^{[13
,14
,15
,16
]}

Pavlovic, Guillaume ^{[13
,14
,15
,16
]}

Bower, Lynette R. ^{[17
]}

Moore, Mark ^{[18
]}

Morse, Iva ^{[19
]}

Gao, Xiang ^{[20
,21
]}

Tocchini-Valentini, Glauco P. ^{[22
]}

Obata, Yuichi ^{[23
]}

Cho, Soo Young ^{[24
,25
]}

Seong, Je Kyung ^{[24
,26
]}

Seavitt, John ^{[11
]}

Beaudet, Arthur L. ^{[11
]}

Dickinson, Mary E. ^{[11
]}

Herault, Yann ^{[13
,14
,15
,16
]}

Wurst, Wolfgang ^{[12
]}

de Angelis, Martin Hrabe ^{[12
]}

Lloyd, K. C. Kent ^{[17
]}

Flenniken, Ann M. ^{[27
]}

Nutter, Lauryl M. J. ^{[27
]}

Newbigging, Susan ^{[27
]}

McKerlie, Colin ^{[27
]}

Justice, Monica J. ^{[28
]}

机构：

[1] European Bioinformat Inst, European Mol Biol Lab, Hinxton, England

[2] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA

[3] Queen Mary Univ London, William Harvey Res Inst, London, England

[4] Wellcome Trust Sanger Inst, Hinxton, England

[5] Med Res Council Harwell, Mammalian Genet Unit, Harwell, Berks, England

[6] Mary Lyon Ctr, Harwell, Berks, England

[7] Oregon Hlth & Sci Univ, Dept Med Informat, Portland, OR 97201 USA

[8] Oregon Hlth & Sci Univ, Clin Epidemiol, Portland, OR 97201 USA

[9] Oregon Hlth & Sci Univ, OHSU Lib, Portland, OR 97201 USA

[10] Lawrence Berkeley Natl Lab, Div Environm Genom & Syst Biol, Berkeley, CA USA

[11] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[12] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany

[13] ICS, PHENOMIN, CELPHEDIA, Illkirch Graffenstaden, France

[14] Univ Strasbourg, IGBMC, Illkirch Graffenstaden, France

[15] Ctr Natl Rech Sci, UMR7104, Illkirch Graffenstaden, France

[16] Inst Natl Sante & Rech Med, U964, Illkirch Graffenstaden, France

[17] Univ Calif Davis, Mouse Biol Program, Davis, CA 95616 USA

[18] IMPC, San Anselmo, CA USA

[19] Charles River Labs, Wilmington, MA USA

[20] Nanjing Univ, SKL Pharmaceut Biotechnol, Nanjing, Jiangsu, Peoples R China

[21] Nanjing Univ, Model Anim Res Ctr, Collaborat Innovat Ctr Genet & Dev, Nanjing Biomed Res Inst, Nanjing, Jiangsu, Peoples R China

[22] Inst Cell Biol & Neurobiol, Italian Natl Res Council, CNR, Monterotondo Mouse Clin, Monterotondo, Italy

[23] RIKEN, BioResource Ctr, Tsukuba, Ibaraki, Japan

[24] Korea Mouse Phenotyping Ctr, Seoul, South Korea

[25] Natl Canc Ctr, Goyang, South Korea

[26] Seoul Natl Univ, Res Inst Vet Sci, Seoul, South Korea

[27] Ctr Phenogen, Toronto, ON, Canada

[28] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON, Canada

[29] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 08期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

GENOME-WIDE; EXPRESSION ATLAS; ONTOLOGY; DATABASE; MICE; ASSOCIATION; GENERATION; RESOURCES; MUTATIONS; ORGANISM;

D O I：

10.1038/ng.3901

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1231 / +

页数：10

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