Genetics and Epigenetics of the Inner Ear: Implications for Hearing and Deafness

Our body contains multiple layers of instructions that define every organ and tissue in our body. These ‘instructions’ include DNA sequences that make up genes, which in turn produce proteins that perform a vast array of functions in our bodies. They also include changes in gene expression that do not involve the DNA sequence but do have a dramatic effect on function. These changes are defined as epigenetics and include DNA methylation and histone modification, as well as non-coding RNAs. Hundreds of genes are expressed in the inner ear, and the proteins they encode are responsible for auditory functions such as endolymphatic fluid composition, secretion of synaptic vesicles, mechanotransduction, endocochlear potential and more. We have identified variants in a portion of these genes that are responsible for hearing loss in Israeli Jewish and Palestinian Arab families. Our most recent work has determined the genome-wide pattern of methylation in the inner ear, leading us to define regulatory networks for sensory epithelium development and hearing onset. We have also discovered thousands of non-coding RNAs in the mammalian inner ear and a portion of their protein targets have been defined, providing insight into the regulation of pathways governing hair cell development and function. This work will guide the development of therapeutics for hearing loss by providing multiple intervention points for manipulation of the auditory system.