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Nat Commun. 2017 Oct 12;8(1):886. doi: 10.1038/s41467-017-00595-4.

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

Collaborators (152)

Allen S, Clementson-Mobbs S, Codner G, Fray M, Gardiner W, Joynson R, Kenyon J, Loeffler J, Nell B, Parker A, Quwailid D, Stewart M, Walling A, Zaman R, Chen CK, Conte N, Matthews P, Relac M, Tudose I, Warren J, Le Marchand E, El Amri A, El Fertak L, Ennah H, Ali-Hadji D, Ayadi A, Wattenhofer-Donze M, Moulaert D, Jacquot S, André P, Birling MC, Pavlovic G, Lalanne V, Lux A, Riet F, Mittelhaeuser C, Bour R, Guimond A, Bam'Hamed C, Leblanc S, Vasseur L, Selloum M, Sorg T, Ayabe S, Furuse T, Kaneda H, Kobayashi K, Masuya H, Miura I, Obata Y, Suzuki T, Tamura M, Tanaka N, Yamada I, Yoshiki A, Berberovic Z, Bubshait M, Cabezas J, Carroll T, Clark G, Clarke S, Creighton A, Danisment O, Eskandarian M, Feugas P, Gertsenstein M, Guo R, Hunter J, Jacob E, Lan Q, Laurin V, Law N, MacMaster S, Miller D, Morikawa L, Newbigging S, Owen C, Penton P, Pereira M, Qu D, Shang X, Sleep G, Sohel K, Tondat S, Wang Y, Vukobradovic I, Zhu Y, Chiani F, Di Pietro C, Di Segni G, Ermakova O, Ferrara F, Fruscoloni P, Gambadoro A, Gastaldi S, Golini E, La Sala G, Mandillo S, Marazziti D, Massimi M, Matteoni R, Orsini T, Pasquini M, Raspa M, Rauch A, Rossi G, Rossi N, Putti S, Scavizzi F, Tocchini-Valentini GD, Beig J, Bürger A, Giesert F, Graw J, Kühn R, Oritz O, Schick J, Seisenberger C, Amarie O, Garrett L, Hölter SM, Zimprich A, Aguilar-Pimentel A, Beckers J, Brommage R, Calzada-Wack J, Fuchs H, Gailus-Durner V, Lengger C, Leuchtenberger S, Maier H, Marschall S, Moreth K, Neff F, Östereicher MA, Rozman J, Steinkamp R, Stoeger C, Treise I, Stoeger T, Yildrim AÖ, Eickelberg O, Becker L, Klopstock T, Ollert M, Busch DH, Schmidt-Weber C, Bekeredjian R, Zimmer A, Rathkolb B, Wolf E, Klingenspor M.

Author information

1
Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
2
King's College London, London, SE1 1UL, UK.
3
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
4
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1 SD, UK.
5
Mouse Biology Program, University of California, Davis, California, 95618, USA.
6
CELPHEDIA, PHENOMIN, Institut Clinique de la Souris (ICS), 1 rue Laurent Fries, Illkirch-Graffenstaden, F-67404, France.
7
RIKEN BioResource Center, Tsukuba, Ibaraki, 305-0074, Japan.
8
The Centre for Phenogenomics, Toronto, Ontario, Canada, M5T 3H7.
9
The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8.
10
Canada and Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5.
11
Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Cell Biology and Neurobiology, I-00015, Monterotondo Scalo, Italy.
12
SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, 210061, Nanjing, China.
13
IMPC, San Anselmo, California, 94960, USA.
14
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA.
15
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, 77030, USA.
16
Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
17
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
18
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, 67404, Illkirch, France.
19
Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
20
Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France.
21
The Jackson Laboratory, Bar Harbor, Maine, 04609, USA.
22
Childrens' Hospital Oakland Research Institute, Oakland, California, 94609, USA.
23
Queen Mary University of London, London, WC1E 6BT, UK.
24
Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK. s.brown@har.mrc.ac.uk.

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.The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

PMID:
29026089
PMCID:
PMC5638796
DOI:
10.1038/s41467-017-00595-4
[Indexed for MEDLINE]
Free PMC Article

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