Dennis Drayna, Ph.D.

Chief
Section on Systems Biology of Communication Disorders
Laboratory of Molecular Genetics

Ph.D., Harvard University, 1981

Research Statement

The Section on Systems Biology of Communication Disorders is focused on identifying genetic variation in the molecular components of human communication systems. Our primary tools are genetic linkage and positional cloning studies, used to identify genes responsible for communication disorders in humans, including deficits in the human sense of taste and the speech disorder of stuttering.

Recent Accomplishments

Sweet taste perception: In a study of a group of 150 normal individuals, we’ve recently shown that specific genetic variants, called SNPs, are associated with sweet taste perception. These variants, which are inherited in a simple fashion, explain approximately 16%, or about 1/6th of the difference between individuals in their ability to sense sucrose and other sweet substances. These genetic variants occur in all populations worldwide, but at different frequencies in different populations. The variant forms, which cause reduced ability to taste sweet substances, are most common in African populations. They occur at moderate frequencies in East Asian populations, and lowest frequencies in Western European populations. These differences are related to varying food choices and food preferences, and provide insights into taste perception as well as factors that control our intake of high-calorie sweet foods. Other large-scale studies are currently underway in an effort to identify other genetic variants that affect sweet taste perception.

Bitter taste deficits: We have focused on deficits in the sense of bitter taste, using the inability to taste phenylthiocarbamide (PTC) as our experimental system. This is the most common sensory deficit in humans, affecting approximately one billion individuals worldwide. Using genetic methods, we have identified the gene responsible for this deficit. This gene encodes a member of the TAS2R bitter taste receptor family, expressed in taste cells on the tongue. The taster form of the gene product differs at three places from the non-taster form. These two forms are of ancient origin and diverged before modern humans migrated out of Africa. Biochemical, anthropological, and molecular structural studies of the different forms of this receptor are currently underway to help provide information about the basic mechanisms of our sense of bitter taste.

View primer sequences for specific amplification of each human bitter taste receptor (Microsoft Excel version).

Stuttering: We study families in which there are many individuals who stutter. Such genetic linkage studies can identify the location of the gene or genes responsible for stuttering in these families. We have enrolled a large group of families in Pakistan, where marriages between cousins are common. Each of these families has multiple cases of stuttering, and our genetic linkage studies identified a major linkage signal on chromosome 12. Additional studies focused on this region of chromosome 12 have identified candidate genes that may be causative of stuttering in these families.

We have also identified a series of large, English-speaking families in Cameroon, West Africa, in which stuttering occurs in approximately half of the family members. Linkage studies in these families are showing promising results, and indicate the location of distinct genes that are causative of stuttering in these families. Identification of such genes would provide insights into the underlying causes of this enigmatic disorder.

Lab Personnel

Changsoo Kang, Ph.D. (Send e-mail)
Alexy Fushan, Ph.D. (Send e-mail)
M. Hashim Raza, B.S. (Send e-mail)
Eduardo Sainz, B.S. (Send e-mail)
Joe Kleinman (Send e-mail)

Selected Publications

• Kim, U.-K., Jorgenson, E., Coon, H., Leppert, M., Risch, N., and Drayna, D. Positional Cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299:1221-1225, 2003.
• Wooding, S., Kim, U.-K., Bamshad, M., Larsen, J., Jorde, L., and Drayna, D. Natural selection and molecular evolution in PTC, a bitter taste receptor gene. American Journal of Human Genetics 74:637-646, 2004.
• Kim, U.-K., Wooding, S., Ricci, D., Jorde, L., and Drayna, D. Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci.Human Mutation 26(3):199-204, 2005.
• Kim, U.-K., Wooding, S., Riaz, N., Jorde, L., and Drayna, D. Variation in the human TAS1R taste receptor genes. Chemical Senses 31:599-611, 2006.
• Shugart, Y.Y., Mundorff, J., Kilshaw, J., Doheny, K., Doan, B., Wanyee, J., Green, E., and Drayna, D.  Results of a genome-wide linkage scan for stuttering. American Journal of Medical Genetics 124A:133-135, 2004.
• Riaz, N., Steinberg S., Ahmad, J., Pluzhnikov, A., Raizuddin, S., Cox, N., and Drayna, D. Genomewide significant linkage to stuttering on chromosome 12. American Journal of Human Genetics 76:647-651, 2005.

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