Genetic Studies of Human Communications Disorders

Deafness &Other Communication Disorders

Investigators

Linked publications & trials

Abstract

In the past year we have discovered that humans vary tremendously in the coding sequence of their individual bitter taste receptor genes. In studies of populations worldwide, we have shown that these 23 genes encode 103 different proteins. Based on our previous studies of one of these genes, the PTC gene that encodes the receptor for bitter thiocyanate-containing compounds, these differences in all the bittter receptors suggest different individuals vary widely in how they perceive bittter tastes. Supporting this view, we have done evolutionary genetic analyses of the PTC gene, and shown that the two major forms of this gene, the taster form and the non-taster form, are both maintained at high frequency worldwide by balancing natural selection. This suggests that the non-taster form serves a useful function that is being selected for. We hypothesize that the non-taster form of this gene encodes a functional receptor for some other toxic bitter substance, not yet recognized. Additional progress was made this year on the genetics of stuttering, where we achieved localization of genes causing stuttering in an inbred Pakistani population, and in a single large family from Cameroon, in equatorial West Africa, in which stuttering occurs as an apparently simple inherited trait. Genome-wide linkage scans followed by computerized statistical analysis have given strong evidence for a gene on chromosome 12 that causes stuttering in a group of Pakistani families, and a gene on chromosome 1 that is causative in our Cameroonian family. Additional genotyping and haplotype analyses are currently under way, to narrow the region in which these genes reside. DS also came to fruition this year with the discovery of a gene that was originally identified as the cause of familial vocal fold paralysis, a disorder that can present life-threatening respiratory compromise at birth. Subsequent clinical work up identified other symptoms of distal motor neuronopathy in these patients. Following mapping of the gene to chromosome 2, we discovered mutations in the dynactin gene as the cause of this disorder. This gene encodes a component on the actin-based intracellular transport within neurons. One hypothesis presented by these results is that this defect occurs due to the failure to transport a factor necessary for neuron growth and survival from the peripheral tissue back to the cell nucleus. These results were published in a report by Puls et al. in Nature Genetics in April of this year.