Follow-up Study: Genomic Regions of Particular Interest

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Kidd, Kenneth, PhD

Our lab has been studying the genetics of Tourette Syndrome (TS) from three separate genetic aspects since 1980. Initially, we used a genetic epidemiological approach and studied the familial patterns of occurrence including twin studies. Those initial studies indicated that a single major gene could be the cause of TS. The studies were extended and further elaborated upon by Dr. David Pauls and the TSA Genetic ConsortiumS members providing today’s more sophisticated understanding of the symptom spectrum among relatives of TS patients. When modern DNA technology began to be developed in the mid80s, our lab switched to a genetic linkage approach to finding a region of some chromosome where that apparent major gene was located. In collaborations with Dr. Roger Kurlan and Dr. David Pauls, we collected samples from several large families with multiple individuals affected with TS across several generations. DNA from these families continues to be studied in the laboratory because our data indicate that the “major gene” that was apparent from statistical analyses of familial patterns of occurrence was an illusion and the genetics of TS is more complex. We are currently finishing a scan of the entire genome in some of those families, and have hints of possible regions that may contain a gene of importance, though not a “major gene.” Those hints are being pursued in additional family material and with additional genetic markers in the regions to determine whether they were just chance occurrences or can be confirmed as indicting a real gene with some effect. In addition, as part of the TSA Genetics Consortium follow-up study, we are testing in these large families multiple genetic markers in the regions suggested by the TSA Genetics Consortium study on affected sib pairs. We hope these efforts will help confirm and refine our Consortium’s findings. Finally, we have been pursuing more basic studies of several of the candidate genes suggested by various prior studies that may be involved in causing TS. Among these are some of the dopaminergic system genes—genes for dopamine receptors and the dopamine transporter. Most of that work has indicated that previous suggestions of involvement were based on an incomplete understanding of the variation that exists among these genes. While we have yet to pinpoint exactly the gene(s) that cause TS, the early work helped document the genetic nature of TS, while the more recent work has helped eliminate false pathways and also provided a sophisticated understanding of several genes of great importance to normal function of the human brain. S TSA continues to provide significant research funding to support the work of the International Consortium—ten centers in six countries are collaborating in this effort. Kenneth K. Kidd, Ph.D. Yale University School of Medicine, New Haven, CT Award $40,000 SAMUEL P. COHEN MEMORIAL AWARD Tourette Association of America Inc. – Research Grant Award 1999-2000