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.

Details

Title
A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction
Author
Bowl, Michael R 1 ; Simon, Michelle M 1 ; Ingham, Neil J 2 ; Greenaway, Simon 1 ; Santos, Luis 1 ; Cater, Heather 1 ; Taylor, Sarah 1 ; Mason, Jeremy 3   VIAFID ORCID Logo  ; Kurbatova, Natalja 3 ; Pearson, Selina 4 ; Bower, Lynette R 5 ; Clary, Dave A 5 ; Meziane, Hamid 6 ; Reilly, Patrick 6 ; Minowa, Osamu 7 ; Kelsey, Lois 8 ; Allen, Sue 1 ; Clementson-Mobbs, Sharon 1 ; Codner, Gemma 1 ; Fray, Martin 1 ; Gardiner, Wendy 1 ; Joynson, Russell 1 ; Kenyon, Janet 1 ; Loeffler, Jorik 1 ; Nell, Barbara 1 ; Parker, Andrew 1 ; Deen Quwailid 1 ; Stewart, Michelle 1 ; Walling, Alison 1 ; Zaman, Rumana 1 ; Chao-Kung, Chen 3 ; Conte, Nathalie 3 ; Matthews, Peter 3 ; Relac, Mike 3 ; Tudose, Ilinca 3 ; Warren, Jonathan 3 ; Elise Le Marchand 6 ; Amal El Amri 6 ; Leila El Fertak 6 ; Ennah, Hamid 6 ; Ali-Hadji, Dalila 6 ; Ayadi, Abdel 6 ; Wattenhofer-Donze, Marie 6 ; Moulaert, David 6 ; Jacquot, Sylvie 6 ; André, Philippe 6 ; Marie-Christine Birling 6 ; Pavlovic, Guillaume 6 ; Lalanne, Valérie 6 ; Lux, Aline 6 ; Riet, Fabrice 6 ; Mittelhaeuser, Christophe 6 ; Bour, Raphael 6 ; Guimond, Alain 6 ; Chaouki Bam’Hamed 6 ; Leblanc, Sophie 6 ; Vasseur, Laurent 6 ; Selloum, Mohammed 6 ; Sorg, Tania 6 ; Ayabe, Shinya 7 ; Furuse, Tamio 7 ; Kaneda, Hideki 7 ; Kobayashi, Kimio 7 ; Masuya, Hiroshi 7 ; Miura, Ikuo 7 ; Obata, Yuichi 7 ; Suzuki, Tomohiro 7 ; Tamura, Masaru 7 ; Tanaka, Nobuhiko 7 ; Yamada, Ikuko 7 ; Yoshiki, Atsushi 7 ; Berberovic, Zorana 8 ; Bubshait, Mohammed 8 ; Cabezas, Jorge 8 ; Carroll, Tracy 8 ; Clark, Greg 8 ; Clarke, Shannon 8 ; Creighton, Amie 8 ; Danisment, Ozge 8 ; Eskandarian, Mohammad 8 ; Feugas, Patricia 8 ; Gertsenstein, Marina 8 ; Guo, Ruolin 8 ; Hunter, Jane 8 ; Jacob, Elsa 8 ; Lan, Qing 8 ; Laurin, Valerie 8 ; Law, Napoleon 8 ; MacMaster, Sue 8 ; Miller, David 8 ; Morikawa, Lily 8 ; Newbigging, Susan 8 ; Owen, Celeste 8 ; Penton, Patricia 8 ; Pereira, Monica 8 ; Qu, Dawei 8 ; Shang, Xueyuan 8 ; Sleep, Gillian 8 ; Khondoker Sohel 8 ; Tondat, Sandra 8 ; Wang, Yanchun 8 ; Vukobradovic, Igor 8 ; Zhu, Yingchun 8 ; Chiani, Francesco 9 ; Chiara Di Pietro 9 ; Gianfranco Di Segni 9 ; Ermakova, Olga 9 ; Ferrara, Filomena 9 ; Fruscoloni, Paolo 9 ; Gambadoro, Aalessia 9 ; Gastaldi, Serena 9 ; Golini, Elisabetta 9 ; Gina La Sala 9 ; Mandillo, Silvia 9 ; Marazziti, Daniela 9 ; Massimi, Marzia 9 ; Matteoni, Rafaele 9 ; Orsini, Tiziana 9 ; Pasquini, Miriam 9 ; Raspa, Marcello 9 ; Rauch, Aline 9 ; Rossi, Gianfranco 9 ; Rossi, Nicoletta 9 ; Putti, Sabrina 9 ; Scavizzi, Ferdinando 9 ; Tocchini-Valentini, Giuseppe D 9 ; Beig, Joachim 10 ; Bürger, Antje 10 ; Giesert, Florian 10 ; Graw, Jochen 10 ; Kühn, Ralf 10 ; Oritz, Oskar 10 ; Schick, Joel 10 ; Seisenberger, Claudia 10 ; Amarie, Oana 11 ; Garrett, Lillian 11 ; Hölter, Sabine M 11 ; Zimprich, Annemarie 11 ; Aguilar-Pimentel, Antonio 12 ; Beckers, Johannes 12 ; Brommage, Robert 12 ; Calzada-Wack, Julia 12 ; Fuchs, Helmut 12 ; Gailus-Durner, Valérie 12 ; Lengger, Christoph 12 ; Leuchtenberger, Stefanie 12 ; Maier, Holger 12 ; Marschall, Susan 12 ; Moreth, Kristin 12 ; Neff, Frauke 12 ; Östereicher, Manuela A 12 ; Rozman, Jan 12 ; Steinkamp, Ralph 12 ; Stoeger, Claudia 12 ; Treise, Irina 12 ; Stoeger, Tobias 13 ; Ali Önder Yildrim 13 ; Eickelberg, Oliver 14 ; Becker, Lore 15 ; Klopstock, Thomas 16 ; Ollert, Markus 17 ; Busch, Dirk H 18 ; Schmidt-Weber, Carsten 19 ; Bekeredjian, Raffi 20 ; Zimmer, Andreas 21 ; Rathkolb, Birgit 22 ; Wolf, Eckhard 23 ; Klingenspor, Martin 24 ; Tocchini-Valentini, Glauco P 9 ; Gao, Xiang 25 ; Bradley, Allan 4 ; Skarnes, William C 4 ; Moore, Mark 26 ; Beaudet, Arthur L 27 ; Justice, Monica J 28 ; Seavitt, John 27 ; Dickinson, Mary E 29 ; Wurst, Wolfgang 10 ; Martin Hrabe de Angelis 12   VIAFID ORCID Logo  ; Herault, Yann 30   VIAFID ORCID Logo  ; Wakana, Shigeharu 7   VIAFID ORCID Logo  ; Nutter, Lauryl M J 8 ; Flenniken, Ann M 8 ; McKerlie, Colin 8   VIAFID ORCID Logo  ; Murray, Stephen A 31 ; Svenson, Karen L 31 ; Braun, Robert E 31 ; West, David B 32 ; Lloyd, K C Kent 5   VIAFID ORCID Logo  ; Adams, David J 4 ; White, Jacqui 4 ; Karp, Natasha 4 ; Flicek, Paul 3   VIAFID ORCID Logo  ; Smedley, Damian 33   VIAFID ORCID Logo  ; Meehan, Terrence F 3 ; Parkinson, Helen E 3 ; Teboul, Lydia M 1 ; Wells, Sara 1 ; Steel, Karen P 2 ; Mallon, Ann-Marie 1 ; Brown, Steve D M 1 

 Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, UK 
 King’s College London, London, UK; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK 
 European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK 
 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK 
 Mouse Biology Program, University of California, Davis, California, USA 
 CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch-Graffenstaden, France 
 RIKEN BioResource Center, Tsukuba, Ibaraki, Japan 
 The Centre for Phenogenomics, Toronto, Ontario, Canada; The Hospital for Sick Children, Toronto, Ontario, Canada; Canada and Mount Sinai Hospital, Toronto, Ontario, Canada 
 Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, Monterotondo Scalo, Italy 
10  Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany 
11  Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany 
12  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany 
13  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany; Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Lung Research, Gießen, Germany 
14  Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Lung Research, Gießen, Germany 
15  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany; Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany 
16  Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München, Munich, Germany 
17  Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark 
18  Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany 
19  Center of Allergy & Environment (ZAUM), Technische Universität München, and Helmholtz Zentrum München, Ingolstaedter Landstrasse, Neuherberg, Germany 
20  Department of Cardiology, University of Heidelberg, Heidelberg, Germany 
21  Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, Bonn, Germany 
22  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany; Ludwig-Maximilians-Universität München, Gene Center, Institute of Molecular Animal Breeding and Biotechnology, Munich, Germany 
23  Ludwig-Maximilians-Universität München, Gene Center, Institute of Molecular Animal Breeding and Biotechnology, Munich, Germany 
24  Institute for Food and Health, Technical University Munich, Freising-Weihenstephan, Germany 
25  SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China 
26  IMPC, San Anselmo, California, USA 
27  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA 
28  The Centre for Phenogenomics, Toronto, Ontario, Canada; The Hospital for Sick Children, Toronto, Ontario, Canada; Canada and Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA 
29  Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA 
30  CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch-Graffenstaden, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, Illkirch, France 
31  The Jackson Laboratory, Bar Harbor, Maine, USA 
32  Childrens’ Hospital Oakland Research Institute, Oakland, California, USA 
33  Queen Mary University of London, London, UK 
Pages
1-11
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1950401967
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.