Genetic Linkage and Positional Cloning Studies in Human Communications Disorders

Deafness &Other Communication Disorders

Investigators

Linked publications & trials

Abstract

In the past year, significant progress was made in all three areas of research within the overall mission of our laboratory, which is genetic studies of human communication disorders. Genetics of stuttering Our research in stuttering consists of a genetic linkage study, designed to identify the location of genes which predispose individuals to stuttering in family clusters of this disorder. The first phase of this study is investigating 234 individuals from 100 different families, each of which contains at least two family members who stutter beyond young childhood. In collaboration with the Center for Inherited Disease Research at Johns Hopkins University, we initiated genotyping in these individuals at 385 markers across the length of all the chromosomes in January of 2000. Genotyping was essentially complete by June of 2000, and data checking and reconciliation of inconsistencies was completed in the subsequent two months. In September, statistical analysis of the data was initiated. This analysis will examine each marker individually to look for any which show co-inheritance with stuttering in families. Such co-inheritance would indicate that a gene which predisposes individuals to stuttering resides in the immediate vicinity of the marker, and will serve as a starting point to identify and understand the gene(s) involved. Genetics of pitch recognition Perception of the pitch requires both the ear, which receives auditory signals, and the brain, which performs substantial processing of auditory signals to produce a perceived pitch. In an effort to understand the molecular and cellular mechanisms of this process, we have sought to determine whether variation in pitch perception abilities is due to genetic causes. In collaboration with the Twins Research Unit at St. Thomas? Hospital, London, we performed a twin study of pitch recognition to determine the relative contribution of genes and environment to variation in human pitch recognition abilities. We used a Distorted Tunes Test, which measures subjects? abilities to identify a wrong note in a popular melody, and tested 136 pairs of identical twins (who share all their genes) and 148 pairs of fraternal twins (who share half their genes), for a total of 568 individuals. Analysis of the results indicated high heritability of variation in pitch recognition, ranging from .71 to .80 depending on how subjects are categorized. The effect of shared environment was zero, indicating that pitch perception ability is not primarily due to learning in the family setting. Scores on the Distorted Tunes Test showed little correlation with measures of peripheral hearing, suggesting that variation in musical pitch recognition is primarily due to highly heritable differences in central auditory function. Genetics of deficits in bitter taste perception About 25% of the U.S. population is unable to taste a class of compounds exemplified by phenylthioarbamide (PTC), which tastes highly bitter to the remainder of the population. This taste deficit is one of the classical simply inherited traits in humans, and is a textbook example of single gene recessive disorder. In collaboration with the University of Utah, we have investigated the PTC taste abilities of the original C.E.P.H. families, which were intensively studied in the 1980?s and 1990?s for the construction of the normal human genetic linkage map. In testing the first 16 families, we identified 7 with PTC non-tasters, and performed linkage analysis using the large amount of existing genotype data in these families from previous studies. We identified strong evidence for linkage at 3 different places in the genome, indicating that at least 3 different genes can cause this deficit, and demonstrating that the classical view of a single-gene disorder is incorrect. Studies are now ongoing to identify the causative genes at these three locations, to help elucidate the components of the bitter taste pathway in humans.