Molecular Genetics and Pathobiology of Deafness
The process of hearing, the acquisition and transduction of sound from the ear to the auditory cortex, is immensely complex involving several tissue types, and this complexity is reflected in the genetic repertoire that is responsible for its development and function. It is estimated that worldwide >250 million people suffer moderate to profound hearing loss, of which half have a genetic basis. There are two main types of hearing impairment; conductive hearing loss which is an impairment resulting from dysfunction in the mechanism of sound wave conduction from the outer ear, through the middle ear, to the inner ear, as occurs in the condition otitis media; and sensorineural hearing loss which is an impairment resulting from dysfunction in the inner ear, auditory nerve, or auditory cortex of the brain. The majority of sensorineural deafness is associated with abnormalities of the hair cells in the organ of Corti in the cochlea, which convert sound vibrations into neural signals.
Deafness can occur early in life with around 1 in 1000 children affected, which can result in delayed development of speech, language and cognitive skills, and may result in slow learning and difficulty progressing in school. In addition, hearing loss can manifest as a late-onset condition called presbycusis, with an estimated 25% of people aged 65-75, and 70-80% of people over age 75 suffering from hearing impairment, which has psychological, physical and social consequences. To date, ~130 loci that cause non-syndromic hearing impairment have been mapped in the human genome (http://webh01.ua.ac.be/hhh/), although the genes underlying >50% of these loci have not been identified, and as such we are far from determining a complete picture of the genetic networks underlying the auditory system.
The deafness group at Harwell continues to make very significant advances in the understanding of the development, transduction and homeostasis of the auditory system, employing the Harwell ENU mutagenesis pipelines we utilize the similarities between the mouse and human genomes, and between the physiology and anatomy of their auditory systems, for the discovery and characterization of genes involved in hearing impairment. Our research focuses on four major areas of genetic deafness: