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Genome-wide association study identifies nox3 as a critical gene for susceptibility to noise-induced hearing loss.

التفاصيل البيبلوغرافية
العنوان: Genome-wide association study identifies nox3 as a critical gene for susceptibility to noise-induced hearing loss.
المؤلفون: Joel Lavinsky, Amanda L Crow, Calvin Pan, Juemei Wang, Ksenia A Aaron, Maria K Ho, Qingzhong Li, Pehzman Salehide, Anthony Myint, Maya Monges-Hernadez, Eleazar Eskin, Hooman Allayee, Aldons J Lusis, Rick A Friedman
المصدر: PLoS Genetics, Vol 11, Iss 4, p e1005094 (2015)
بيانات النشر: Public Library of Science (PLoS), 2015.
سنة النشر: 2015
المجموعة: LCC:Genetics
مصطلحات موضوعية: Genetics, QH426-470
الوصف: In the United States, roughly 10% of the population is exposed daily to hazardous levels of noise in the workplace. Twin studies estimate heritability for noise-induced hearing loss (NIHL) of approximately 36%, and strain specific variation in sensitivity has been demonstrated in mice. Based upon the difficulties inherent to the study of NIHL in humans, we have turned to the study of this complex trait in mice. We exposed 5 week-old mice from the Hybrid Mouse Diversity Panel (HMDP) to a 10 kHz octave band noise at 108 dB for 2 hours and assessed the permanent threshold shift 2 weeks post exposure using frequency specific stimuli. These data were then used in a genome-wide association study (GWAS) using the Efficient Mixed Model Analysis (EMMA) to control for population structure. In this manuscript we describe our GWAS, with an emphasis on a significant peak for susceptibility to NIHL on chromosome 17 within a haplotype block containing NADPH oxidase-3 (Nox3). Our peak was detected after an 8 kHz tone burst stimulus. Nox3 mutants and heterozygotes were then tested to validate our GWAS. The mutants and heterozygotes demonstrated a greater susceptibility to NIHL specifically at 8 kHz both on measures of distortion product otoacoustic emissions (DPOAE) and on auditory brainstem response (ABR). We demonstrate that this sensitivity resides within the synaptic ribbons of the cochlea in the mutant animals specifically at 8 kHz. Our work is the first GWAS for NIHL in mice and elucidates the power of our approach to identify tonotopic genetic susceptibility to NIHL.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1553-7390
1553-7404
94782504
Relation: http://europepmc.org/articles/PMC4399881?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404
DOI: 10.1371/journal.pgen.1005094
URL الوصول: https://doaj.org/article/94782504ad8043708b393a68af904bc6
رقم الأكسشن: edsdoj.94782504ad8043708b393a68af904bc6
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:15537390
15537404
94782504
DOI:10.1371/journal.pgen.1005094