Steel_Exomes

One of the tests carried out on knockout mice generated by the Mouse Genome Project is the Auditory Brainstem Response, a highly sensitive test capable of detecting subtle hearing defects. Recently, multiple mice have been found which displayed a variety of hearing defects which did not segregate with the knockout allele, and were probably due to spontaneous mutations. We have successfully rescued some of the observed phenotypes and have six breeding colonies showing a range of interesting hearing defects. Here we exome sequence two mice from each of these colonies to locate the causative mutation. Sequencing two individuals means mutations unique to one mouse can be discounted and only those mutations common to both affected mice considered, speeding up the process of checking the candidate mutations. Some of the phenotypes are particularly unusual, and finding the gene responsible will offer new insight into the genetic mechanisms of hearing and deafness.