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

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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, Sue Allen, Sharon Clementson-Mobbs, Gemma Codner, Martin Fray & 181 others Wendy Gardiner, Russell Joynson, Janet Kenyon, Jorik Loeffler, Barbara Nell, Andrew Parker, Deen Quwailid, Michelle Stewart, Alison Walling, Rumana Zaman, Chao Kung Chen, Nathalie Conte, Peter Matthews, Mike Relac, Ilinca Tudose, Jonathan Warren, Elise Le Marchand, Amal El Amri, Leila El Fertak, Hamid Ennah, Dalila Ali-Hadji, Abdel Ayadi, Marie Wattenhofer-Donze, David Moulaert, Sylvie Jacquot, Philippe André, Marie Christine Birling, Guillaume Pavlovic, Valérie Lalanne, Aline Lux, Fabrice Riet, Christophe Mittelhaeuser, Raphael Bour, Alain Guimond, Chaouki Bam'Hamed, Sophie Leblanc, Laurent Vasseur, Mohammed Selloum, Tania Sorg, Shinya Ayabe, Tamio Furuse, Hideki Kaneda, Kimio Kobayashi, Hiroshi Masuya, Ikuo Miura, Yuichi Obata, Tomohiro Suzuki, Masaru Tamura, Nobuhiko Tanaka, Ikuko Yamada, Atsushi Yoshiki, Zorana Berberovic, Mohammed Bubshait, Jorge Cabezas, Tracy Carroll, Greg Clark, Shannon Clarke, Amie Creighton, Ozge Danisment, Mohammad Eskandarian, Patricia Feugas, Marina Gertsenstein, Ruolin Guo, Jane Hunter, Elsa Jacob, Qing Lan, Valerie Laurin, Napoleon Law, Sue MacMaster, David Miller, Lily Morikawa, Susan Newbigging, Celeste Owen, Patricia Penton, Monica Pereira, Dawei Qu, Xueyuan Shang, Gillian Sleep, Khondoker Sohel, Sandra Tondat, Yanchun Wang, Igor Vukobradovic, Yingchun Zhu, Francesco Chiani, Chiara Di Pietro, Gianfranco Di Segni, Olga Ermakova, Filomena Ferrara, Paolo Fruscoloni, Aalessia Gambadoro, Serena Gastaldi, Elisabetta Golini, Gina La Sala, Silvia Mandillo, Daniela Marazziti, Marzia Massimi, Rafaele Matteoni, Tiziana Orsini, Miriam Pasquini, Marcello Raspa, Aline Rauch, Gianfranco Rossi, Nicoletta Rossi, Sabrina Putti, Ferdinando Scavizzi, Giuseppe D. Tocchini-Valentini, Joachim Beig, Antje Bürger, Florian Giesert, Jochen Graw, Ralf Kühn, Oskar Oritz, Joel Schick, Claudia Seisenberger, Oana Amarie, Lillian Garrett, Sabine M. Hölter, Annemarie Zimprich, Antonio Aguilar-Pimentel, Johannes Beckers, Robert Brommage, Julia Calzada-Wack, Helmut Fuchs, Valérie Gailus-Durner, Christoph Lengger, Stefanie Leuchtenberger, Holger Maier, Susan Marschall, Kristin Moreth, Frauke Neff, Manuela A. Östereicher, Jan Rozman, Ralph Steinkamp, Claudia Stoeger, Irina Treise, Tobias Stoeger, Ali Önder Yildrim, Oliver Eickelberg, Lore Becker, Thomas Klopstock, Markus Ollert, Dirk H. Busch, Carsten Schmidt-Weber, Raffi Bekeredjian, Andreas Zimmer, Birgit Rathkolb, Eckhard Wolf, Martin Klingenspor, 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 De 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, Steve D.M. Brown

Original languageEnglish
Article number886
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2017

King's Authors

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.

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