Genetic Linkage And Positional Cloning Studies In Human

Deafness &Other Communication Disorders

Investigators

Linked publications, trials & patents

Abstract

During the past year we have made significant findings in several different areas. In the area of genetics of chemosensory deficits, we have identified the genetic alteration which causes the inability to taste the substance phenylthiocarbamide (PTC). This trait is one of the best studied inherited traits in humans, and has served as a model system for both genetics and anthropology studies for over 70 years. We have discovered a variant form of a taste receptor gene, located on chromosome 7q, that accounts for 55-85% of the variation in PTC taste sensitivity in humans. Although our primate studies indicate this variant arose after the divergence of humans from other primates, haplotype studies indicate an ancient, probably African origin for this variant, with subsequent spread to other populations worldwide. Five different forms of this gene product occur in the current worldwide population, and we are expressing these 5 forms for in vitro studies of G-protein coupled receptor function. In the area of genetics of communication disorders, we have discovered a large family (>100 individuals) in which persistent stuttering is apparently transmitted as a simple genetic trait. We have obtained blood samples for DNA and speech samples on 45 affected members of this family, along with control normal samples from this population, which is in West Africa. We have inititated genotyping for a genome-wide genetic linkage study, in an effort to localize the gene responsible for stuttering in this family. We are performing a similar study in a group of 40 highly consanguineous satuttering families from Pakistan, and in the past year we have surveyed approximately 1/3 of the genome. In our studies of deficits in auditory pitch processing, we have found a total of 40 individuals with reproducible deficits in the ability to identify musical pitch, or tone. For more than 30 of these individuals, we have tested other members of their family, and in approximately half of the cases, found additional family members with similar deficits. We are expanding studies in these families, to both identify additional individuals and to better characterize the nature of the auditory deficit in these individuals.