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

Michael R. Bowl, Michelle M. Simon, Neil J. Ingham, Simon Greenaway, Luis Santos, Heather Cater, Sarah Taylor, Jeremy Mason, Natalja Kurbatova, Selina Pearson, Lynette R. Bower, Dave A. Clary, Hamid Meziane, Patrick Reilly, Osamu Minowa, Lois Kelsey, Glauco P. Tocchini-Valentini, Xiang Gao, Allan Bradley, William C. Skarnes, Mark Moore, Arthur L. Beaudet, Monica J. Justice, John Seavitt, Mary E. Dickinson, Wolfgang Wurst, Martin Hrabe Angelis, Yann Herault, Shigeharu Wakana, Lauryl M. J. Nutter, Ann M. Flenniken, Colin McKerlie, Stephen A. Murray, Karen L. Svenson, Robert E. Braun, David B. West, K. C. Kent Lloyd, David J. Adams, Jacqui White, Natasha Karp, Paul Flicek, Damian Smedley, Terrence F. Meehan, Helen E. Parkinson, Lydia M. Teboul, Sara Wells, Karen P. Steel, Ann-Marie Mallon and Steve D. M. Brown ()
Additional contact information
Michael R. Bowl: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Michelle M. Simon: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Neil J. Ingham: King’s College London
Simon Greenaway: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Luis Santos: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Heather Cater: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Sarah Taylor: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Jeremy Mason: Wellcome Trust Genome Campus
Natalja Kurbatova: Wellcome Trust Genome Campus
Selina Pearson: Wellcome Trust Genome Campus
Lynette R. Bower: University of California
Dave A. Clary: University of California
Hamid Meziane: Institut Clinique de la Souris (ICS)
Patrick Reilly: Institut Clinique de la Souris (ICS)
Osamu Minowa: RIKEN BioResource Center
Lois Kelsey: The Centre for Phenogenomics
Glauco P. Tocchini-Valentini: Institute of Cell Biology and Neurobiology
Xiang Gao: Nanjing University
Allan Bradley: Wellcome Trust Genome Campus
William C. Skarnes: Wellcome Trust Genome Campus
Mark Moore: IMPC
Arthur L. Beaudet: Baylor College of Medicine
Monica J. Justice: The Centre for Phenogenomics
John Seavitt: Baylor College of Medicine
Mary E. Dickinson: Baylor College of Medicine
Wolfgang Wurst: Helmholtz Zentrum München, German Research Center for Environmental Health GmbH
Martin Hrabe Angelis: German Research Center for Environmental Health GmbH
Yann Herault: Institut Clinique de la Souris (ICS)
Shigeharu Wakana: RIKEN BioResource Center
Lauryl M. J. Nutter: The Centre for Phenogenomics
Ann M. Flenniken: The Centre for Phenogenomics
Colin McKerlie: The Centre for Phenogenomics
Stephen A. Murray: The Jackson Laboratory
Karen L. Svenson: The Jackson Laboratory
Robert E. Braun: The Jackson Laboratory
David B. West: Childrens’ Hospital Oakland Research Institute
K. C. Kent Lloyd: University of California
David J. Adams: Wellcome Trust Genome Campus
Jacqui White: Wellcome Trust Genome Campus
Natasha Karp: Wellcome Trust Genome Campus
Paul Flicek: Wellcome Trust Genome Campus
Damian Smedley: Queen Mary University of London
Terrence F. Meehan: Wellcome Trust Genome Campus
Helen E. Parkinson: Wellcome Trust Genome Campus
Lydia M. Teboul: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Sara Wells: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Karen P. Steel: King’s College London
Ann-Marie Mallon: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)
Steve D. M. Brown: Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre)

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00595-4

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