The Genomics of Auditory Function and Disease

Abstract

Current estimates suggest that nearly half a billion people worldwide are affected by hearing loss. Because of the major psychological, social, economic, and health ramifications, considerable efforts have been invested in identifying the genes and molecular pathways involved in hearing loss, whether genetic or environmental, to promote prevention, improve rehabilitation, and develop therapeutics. Genomic sequencing technologies have led to the discovery of genes associated with hearing loss. Studies of the transcriptome and epigenome of the inner ear have characterized key regulators and pathways involved in the development of the inner ear and have paved the way for their use in regenerative medicine. In parallel, the immense preclinical success of using viral vectors for gene delivery in animal models of hearing loss has motivated the industry to work on translating such approaches into the clinic. Here, we review the recent advances in the genomics of auditory function and dysfunction, from patient diagnostics to epigenetics and gene therapy.

Keywords: deafness; epigenetics; gene therapy; genomics; hearing loss; regeneration.

Figure 1

Schematic illustration of the auditory system.

Figure 2

Genes involved in nonsyndromic hearing loss (114) and their positions on human chromosomes.

Figure 3

Schematic illustration of genomic structure and the interactions among regulatory elements. Abbreviations: lncRNA, long noncoding RNA; miRNA, microRNA; TAD, topologically associating domain; UTR, untranslated region.

Figure 4

Example of a results page from the gEAR website (https://umgear.org), which provides a centralized portal for sharing, visualization, and analysis of multiomic data in the ear research field. Each data set is represented in a box that allows access to further information and analysis tools, and a variety of data sets and multiomic modalities can be represented on one page. With more than 1,300 registered users and 879 data sets, gEAR has transformed the culture of and access to data sharing in the field. Abbreviation: gEAR, Gene Expression Analysis Resource.

Figure 5

Strategies and modalities of inner-ear therapy.