Functional Genomic Analysis of Genes for Deafness

Hearing is one of the most complex processes in the human body where the three parts of the ear work in harmony to transmit the signals to the brain. To date, pathogenic variants in over 200 genes have been associated with hearing impairment. Given the complexity of the hearing process, it is predicted that there are more genes yet to be discovered. The recent advances in next generation sequencing over the past decade have facilitated rapid gene discovery, paving the way to achieve precision medicine for deafness. Our research aims at expanding our knowledge of the spectrum and frequency of hearing loss- associated genes in the Israeli Jewish and Palestinian Arab populations. In our latest project, we have applied whole exome sequencing (WES) for 1089 deaf probands from the Israeli Jewish population, with audiograms documenting the severity of hearing impairment. Following in-depth bioinformatics analysis, using our in-house pipeline (in collaboration with Prof. Noam Shomron, Tel Aviv University), pathogenic variants are being evaluated to determine genotype-phenotype-ethnicity correlations and novel variants are being functionally characterized using in-vitro cell culture assays. Additionally, we aim at understanding the mechanism of pathogenesis of novel genes and their role in the auditory system by using spontaneously and ENU-induced and CRISPR mutant mouse mutants as models for human deafness. We hope that this study will contribute to further understanding of the pathogenesis of hearing loss worldwide and to the implementation of precision medicine in the field of hearing loss. This will also serve as potential candidates for gene therapy, which is already implemented in our laboratory.