Approved Research

Identification of novel copy number variants involved in deafness phenotypes using whole-genome sequencing data

Lay summary

Hearing loss is the most common sensory disorder, affecting approximately one in 500 newborns worldwide. Genetic causes are estimated to be responsible for hearing loss in newborns in up to 60% of cases, yet the majority of individuals who are born deaf never receive a diagnosis that explains why. This is partly due to the complex nature of the genetics of hearing, with hundreds of genes known to be involved in the process of hearing. Pinpointing the genetic mutations that cause deafness in an individual has been challenging. As sequencing of the whole genome becomes more economical, new opportunities arise to uncover previously hard to find and clinically relevant mutations. Previous studies have primarily focused on mutations that change only a single base pair in the DNA sequence, but there is emerging evidence that larger insertions or deletions of DNA may play a substantial role in causing disease. However, there is an urgent need to develop effective computational methods to detect these insertions or deletions in such large datasets generated by sequencing of the whole genome. This project seeks to apply a new computational method to improve detection of deafness-causing mutations in 130 individuals who are deaf. This method will provide clinicians with new tools to find diagnostically relevant mutations for complex genetic disorders such as hearing loss and equip individuals with understanding the genetic basis of their deafness.