The relative contribution of heredity to age-related hearing loss is not known, however the majority of inherited late-onset deafness is autosomal dominant and non-syndromic. Over 50 genes associated with autosomal dominant non-syndromic hearing loss (ADNSHL) have been localized and of these, 21 have been cloned. Although the function of many of these genes in the inner ear is unclear, an understanding of the biology of hearing and deafness at a molecular level is emerging. In this competitive renewal, we propose to continue our work localizing and cloning genes that cause ADNSHL. We will also expand the phenotype-genotype studies we have done to facilitate gene identification in small families and continue the RNA interference experiments we initiated to explore novel treatment options for select types of hearing loss.
The specific aims of this proposal are: 1) Specific Aim 1: To continue to localize and clone genes that cause ADNSHL; 2) Specific Aim 2: To develop audioprofiling as a method to prioritize genes for mutation screening in families segregating ADNSHL but with an insufficient number of informative meioses for linkage analysis; 3) Specific Aim 3: To test the efficacy of RNA interference as a potential therapy in modifying the hearing loss phenotype in a type of ADNSHL caused by a dominant-negative mechanism of action. Completion of these specific aims will not only increase our understanding of the pathogenesis of deafness, but will be highly translational by targeting small families segregating ADNSHL. Most inherited late-onset deafness is autosomal dominant and non-syndromic. Over 50 genes associated with autosomal dominant non-syndromic hearing loss (ADNSHL) have been localized and of these, 21 have been cloned. Studying these genes will increase our understanding of deafness and ultimately lead to novel methods of preventing ADNSHL.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Genetics of Health and Disease Study Section (GHD)
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Watson, Bracie
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University of Iowa
Schools of Medicine
Iowa City
United States
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Booth, Kevin T; Azaiez, Hela; Kahrizi, Kimia et al. (2018) Exonic mutations and exon skipping: Lessons learned from DFNA5. Hum Mutat 39:433-440
Matern, Maggie S; Beirl, Alisha; Ogawa, Yoko et al. (2018) Transcriptomic Profiling of Zebrafish Hair Cells Using RiboTag. Front Cell Dev Biol 6:47
Booth, K T; Kahrizi, K; Babanejad, M et al. (2018) Variants in CIB2 cause DFNB48 and not USH1J. Clin Genet 93:812-821
Booth, Kevin T; Kahrizi, Kimia; Najmabadi, Hossein et al. (2018) Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment. J Med Genet 55:555-560
Booth, Kevin T; Askew, James W; Talebizadeh, Zohreh et al. (2018) Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37. Genet Med :
Azaiez, Hela; Booth, Kevin T; Ephraim, Sean S et al. (2018) Genomic Landscape and Mutational Signatures of Deafness-Associated Genes. Am J Hum Genet 103:484-497
Song, Yang; Milon, Beatrice; Ott, Sandra et al. (2018) A comparative analysis of library prep approaches for sequencing low input translatome samples. BMC Genomics 19:696
Milon, BĂ©atrice; Mitra, Sunayana; Song, Yang et al. (2018) The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice. Biol Sex Differ 9:12
Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J et al. (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780-798
Yoshimura, Hidekane; Shibata, Seiji B; Ranum, Paul T et al. (2018) Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation. Sci Rep 8:2980

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