MOLECULAR GENETICS OF THE AUDITORY SYSTEM

It has been estimated that 50% of all newly identified childhood hearing
losses are genetic in origin. Recent advances in molecular genetics make
possible the isolation and characterization of most genes which influence
the hearing process. Such information will enhance diagnostic accuracy,
improve genetic counseling and lead to more effective methods of therapy.
More importantly, the knowledge gained from these studies will provide
a foundation for major advances in understanding of the molecular
genetics of the auditory system. Progression from localization to
characterization of an individual gene requires a highly integrated
research program. We have assembled the staff and laboratory facilities
required to carry out all stages of the process. A series of projects
are proposed which will allow us to make progress on several genetic
disorders as well as develop the professional relationships and technical
expertise to operate at maximum efficiency. This program project grant brings together four separate projects, each
of which focuses on a different problem related to the molecular genetics
of hearing. The first project will use the exciting new technology of
gene targeting to create a genetically correct mouse model for Alport
Syndrome (nephritis and deafness). As we isolate genes for other hearing
disorders, we will be able to apply the same technology to develop
similar animal models. The second and third projects are directed
towards finding and cloning of the Usher Syndrome type II gene which we
have localized to chromosome 1q. Project four will carry out a genome
search for Branchio-Oto-Renal syndrome. Once the BOR gene is localized,
we intend to apply the techniques outlined in the preceding projects to
determine the molecular basis of that disorder. This program project will bring diverse investigators together to meet
a common goal: the further understanding of the molecular genetic basis
of normal and abnormal hearing. As such, it lays the foundation for
future collaboration between the program investigators and gives the
program a long term commitment to the study of the genetics of hearing
disorders. This is particularly attractive when viewed in the context
of the location of the project: BTNRH has existing auditory research
programs that can take full advantage of the research proposed in this
grant.