Dennis Drayna, Ph.D.
Laboratory of Communication Disorders
Section on Systems Biology of Communication Disorders
Porter Neuroscience Research Center
35A Convent Drive 1F-127
Bethesda, MD 20892-3729 for U.S. Postal Service
Bethesda, MD 20814 for other carriers (FedEx, UPS, etc.)
Telephone: (301) 402-4930 (office)
Ph.D., Harvard University, 1981
In the Section on Systems Biology of Communication Disorders, we use family- and population-based genetic methods to identify genes responsible for human communication disorders. The lab has a major focus on the speech disorder stuttering, for which we have identified causative mutations in several genes. We study the biochemical and cellular effects of these mutations, and we use mouse model systems to study the effects of these mutations on mouse ultrasonic vocalizations. The long-term goal of our work is to identify specific neuronal pathologies caused by these mutations.
We also perform studies on the sense of taste, where our overall goal is understanding how naturally occurring genetic variation contributes to differences in the sense of taste in humans. We are currently focused on a study of variation in taste perception genes and tobacco use, with a particular interest in menthol tobacco use and variation in the TRPM8 gene which encodes the menthol receptor.
Stuttering: We study families in which many individuals stutter. Genetic linkage studies in such families 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 major linkage signals, indicating different causative genes, on chromosomes 12, 3, and 16.
We have also identified a large, English-speaking family in Cameroon, West Africa, in which stuttering occurs in more than 40 family members. Linkage studies in this family have shown that stuttering is due to several different genes, each acting in a different branch of the family. These genes are located on chromosome 2, 3, 14, and 15. Recent studies of stuttering families from Brazil have identified yet another locus, on chromosome 10, that carries a stuttering gene in this population. Identification of the causative genes at these loci will hopefully provide broad insights into the underlying causes of this enigmatic disorder.
Studies of the chromosome 12 locus have identified causative mutations in the gene GNPTAB, and additional studies have identified causative mutations in the related GNPTG and NAGPA genes. Together these genes appear to account for more than 10 percent of stuttering cases in the U.S., as well as elsewhere in the world. Studies of the chromosome 15 locus in the Cameroonian family have identified an additional causative gene, which appears to account for more than 5 percent of stuttering cases in worldwide populations.
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 percent, 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.
Carlos Frigerio Domingues, Ph.D., post-doctoral visiting fellow (Send email)
Joanne Gutierrez, MS, chemist (Send email)
Tae-Un Han, Ph.D., post-doctoral visiting fellow (Send email)
Jessica Root, BS, post-baccalaureate IRTA (Send email)
Davide Risso, MS, pre-doctoral fellow (Send email)
Eduardo Sainz, BS, chemist (Send email)
- Domingues CE, Olivera CMC, Oliveira BV, Juste FS, Andrade CF, Giacheti CM, Moretti-Fereira D, Drayna D. A genetic linkage study in Brazil identifies a new locus for persistent developmental stuttering on chromosome 10. Genetics and Molecular Research 13:2094-2101 (2014)
- Raza MH, Gertz EM, Mundorff J, Lukong J, Kuster J, Schäffer A, Drayna D. Linkage analysis of a large African family segregating stuttering suggests polygenic inheritance and assortative mating. Human Genetics 132:385-396 (2013)
- Raza, MH, Ali RA, Riazuddin S, Drayna D. Studies in a consanguineous family reveal a novel locus for stuttering on chromosome 16q. Human Genetics 131:311-313 (2012)
- Lee W-S, Kang C, Drayna D, Kornfeld S. Analysis of Mannose 6-Phosphate uncovering enzyme mutations associated with persistent stuttering. Journal of Biological Chemistry 286:39786-39793 (2011)
- Raza MH, Riazuddin S, Drayna D. Identification of an autosomal recessive stuttering locus on chromosome 3q13.2-3q13.33. Human Genetics, 128:461-463 (2010)
- Kang C, Riazuddin S, Mundorff J, Krasnewich D, Friedman P, Mullikin JC, Drayna D. Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering. N Engl J Med. 2010 Feb 25;362(8):677-85. Epub 2010 Feb 10.
- Riaz N, Steinberg S, Ahmad J, Pluzhnikov A, Raizuddin S, Cox N, Drayna D. Genomewide significant linkage to stuttering on chromosome 12. American Journal of Human Genetics 76:647-651, 2005.