Big Data to Therapy: Personalized Medicine for the Deaf in the Diverse Jewish Population

Precision medicine is critical for providing medical care for individuals based on their unique variants and phenotypes. The field of hearing loss is now in an optimal position to integrate precision medicine into care for patients. Approximately 5% of the world’s population, or 466 million people, suffer hearing loss. Over 100 genes are involved in deafness worldwide, with specific genes in distinct populations. However, about half of inherited deafness likely remains unsolved. The same is true for the Israeli Jewish population, which includes multiple ethnic groups, turning Israel into a microcosm of genetic diversity that harbors mutations in many deafness genes. We have begun a large-scale study of the hearing-impaired population in Israel, utilizing the Maccabi Tipa Biobank of approximately 100,000 samples. An initial search of 56,000 samples yielded 6,000 individuals suffering from hearing loss. Whole exome sequencing will be performed on all probands fulfilling phenotypic criteria, followed by bioinformatics analysis, variant validation and determination of genotype-phenotype-ethnicity correlations. Novel variants will be immediately applied in the genetics and audiology clinics, setting a guideline for precision medicine for hearing loss in Israel. In parallel, novel variants, including in genes and in regulatory domains, will be functionally investigated, beginning from basic characterization and progressing to advanced experiments of epigenomics, CRISPR-Cas9 gene editing, and gene therapy. Solving the etiology of deafness in the diverse Israeli Jewish population in a large-scale study is the key for diagnosis, prevention and treatment. The research is supported by the Israel Precision Medicine Partnership Program.