The goal of this proposal is to identify molecular basis of non-syndromic deafness by using a multidisciplinary Approach in several unique resources of patients/families from Far Eastern populations. We have a large and expanding collection of genomic DNA from patients/families with non-syndromic deafness from China and Japan First, because of genetic heterogeneity, large multigenerational families and consanguineous families have been selected for study that are independently capable of yielding evidence of for linkage. We will then seek to identify and ultimately clone the relevant genes by the positional candidate gene approach. Second, a novel sequential screening strategy will be used to identify new genes for deafness in probands from multiplex families. Candidate genes to be screened will include the human orthologs of murine genes for deafness and other members of gene families in which some are known to be the cause of deafness. The research will yield important information o ethnic differences in the frequency and distribution of mutations at currently recognized genes for non-syndromic deafness. Using available information on outcome variables such as age of onset, audiologic findings, and the mating structure of the deaf population, these data will permit a search for clinically relevant genotype-phenotype correlations and a clearer understanding of the cause for secular changes in the frequency of specific forms o genetic deafness. Finally, we will use yeast 2-hybrid systems and the immunoaffinity chromatography to search for proteins that interact with the products of the MYO7A and USH1C genes. The identification of such interactions could lead to identifying potential modifiers and exciting new therapeutic approaches to attenuate the specific effects of mutations on the cochlear. The proposed work will identify the new gene (s) for non-syndromic deafness and enable us to understand better cellular and molecular basis of genetic deafness. Our studies will develop a more comprehensive picture of the involvement of genes in non-syndromic deafness to gain further insight into the function of these genes in the inner ear. This knowledge is an essential prerequisite to the development and provision of molecular diagnostic services for families with non-syndromic deafness.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Mammalian Genetics Study Section (MGN)
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Watson, Bracie
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University of Miami School of Medicine
Schools of Medicine
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Mittal, Rahul; Patel, Amit P; Nguyen, Desiree et al. (2018) Genetic basis of hearing loss in Spanish, Hispanic and Latino populations. Gene 647:297-305
Wang, Li; Yan, Denise; Qin, Litao et al. (2018) Amino acid 118 in the Deafness Causing (DFNA20/26) ACTG1 gene is a Mutational Hot Spot. Gene Rep 11:264-269
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