A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

被引：108

作者：

Bowl, Michael R. ^{[1
]}

Simon, Michelle M. ^{[1
]}

Ingham, Neil J. ^{[2
,3
]}

Greenaway, Simon ^{[1
]}

Santos, Luis ^{[1
]}

Cater, Heather ^{[1
]}

Taylor, Sarah ^{[1
]}

Mason, Jeremy ^{[4
]}

Kurbatova, Natalja ^{[4
]}

Pearson, Selina ^{[3
]}

Bower, Lynette R. ^{[5
]}

Clary, Dave A. ^{[5
]}

Meziane, Hamid ^{[6
]}

Reilly, Patrick ^{[6
]}

Minowa, Osamu ^{[7
]}

Kelsey, Lois ^{[8
,9
,10
]}

Tocchini-Valentini, Glauco P. ^{[11
]}

Gao, Xiang ^{[12
]}

Bradley, Allan ^{[3
]}

Skarnes, William C. ^{[3
]}

Moore, Mark ^{[13
]}

Beaudet, Arthur L. ^{[14
]}

Justice, Monica J. ^{[8
,9
,10
,14
]}

Seavitt, John ^{[14
]}

Dickinson, Mary E. ^{[15
]}

Wurst, Wolfgang ^{[16
]}

de Angelis, Martin Hrabe ^{[17
]}

Herault, Yann ^{[6
,18
,19
,20
]}

Wakana, Shigeharu ^{[7
]}

Nutter, Lauryl M. J. ^{[8
,9
,10
]}

Flenniken, Ann M. ^{[8
,9
,10
]}

McKerlie, Colin ^{[8
,9
]}

Murray, Stephen A. ^{[21
]}

Svenson, Karen L. ^{[21
]}

Braun, Robert E. ^{[21
]}

West, David B. ^{[22
]}

Lloyd, K. C. Kent ^{[5
]}

Adams, David J. ^{[3
]}

White, Jacqui

Karp, Natasha ^{[3
]}

Flicek, Paul ^{[4
]}

Smedley, Damian ^{[23
]}

Meehan, Terrence F. ^{[4
]}

Parkinson, Helen E. ^{[4
]}

Teboul, Lydia M. ^{[1
]}

Wells, Sara ^{[1
]}

Steel, Karen P. ^{[2
,3
]}

Mallon, Ann-Marie ^{[1
]}

Brown, Steve D. M. ^{[1
]}

机构：

[1] MRC, Harwell Inst, Mammalian Genet Unit, Harwell OX11 0RD, Oxon, England

[2] Kings Coll London, London SE1 1UL, England

[3] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[4] Wellcome Trust Genome Campus, European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England

[5] Univ Calif Davis, Mouse Biol Program, Davis, CA 95618 USA

[6] Inst Clin Souris ICS, PHENOMIN, CELPHEDIA, 1 Rue Laurent Fries, F-67404 Illkirch Graffenstaden, France

[7] RIKEN BioResource Ctr, Tsukuba, Ibaraki 3050074, Japan

[8] Ctr Phenogenom, Toronto M5T 3H7, ON, Canada

[9] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[10] Canada & Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada

[11] Inst Cell Biol & Neurobiol, Italian Natl Res Council CNR, Monterotondo Mouse Clin, I-00015 Monterotondo, Italy

[12] Nanjing Biomed Res Inst, Collaborat Innovat Ctr Genet & Dev, SKL Pharmaceut Biotechnol & Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China

[13] IMPC, San Anselmo, CA 94960 USA

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

[15] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA

[16] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Dev Genet, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany

[17] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, German Mouse Clin Inst Expt Genet, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany

[18] Univ Strasbourg, IGBMC, F-67404 Illkirch Graffenstaden, France

[19] CNRS, UMR 7104, F-67404 Illkirch Graffenstaden, France

[20] INSERM, U964, F-67404 Illkirch Graffenstaden, France

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

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

[23] Queen Mary Univ London, London WC1E 6BT, England

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国惠康基金; 英国医学研究理事会; 英国生物技术与生命科学研究理事会; 美国国家卫生研究院;

关键词：

OTITIS-MEDIA; GENOME-WIDE; HAIR-CELLS; MOUSE; IMPAIRMENT; MUTAGENESIS; RESOURCE; MUTATION; DISEASE; PROJECT;

D O I：

10.1038/s41467-017-00595-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function.

引用

页数：11

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