Linkage Disequilibrium Mapping of Tourette Syndrome

Grant Type
Basic
Grant Year
1996
Institution Location
CA
Institution Organization Name
University of California
Investigators Name
DeMille, Mellissa M.C., PhD

The goal of our project is to discover the gene(s) that contribute to the susceptibility of having Tourette Syndrome (TS). Our strategy includes the use of a population in Costa Rica to limit the confusion that comes from a “melting pot” population such as that of the United States. Although there are many people in the U.S. who have TS, their genetic backgrounds are very diverse. This diversity can greatly complicate the process of TS gene detection because in such a study different individuals may inherit their individual susceptibility to having TS in many different ways. For example, genes contribut¬ing to a TS vulnerability may have mutated in different ways among individuals in the same family. The central valley of Costa Rica was settled by a small number of Spanish immigrants and American Indian inhabitants. This population subsequently expanded, but in isolation. If one imagines for example, that a single member of the founding families carried the TS susceptibility gene on one of his/her chromosomes, this person would have then passed on this chromosome to some of his/her children who in turn would have passed it on to some of their children. As the population expanded, many copies of this chromo¬some would have spread throughout the population. Therefore, if no other individual carrying a different TS susceptibility gene joined this population, then all of the TS affected in this population would all have some portion of the founder’s chromosome—the part that carries the TS gene. Because most of the individuals with TS in a homogenous population (e.g. the central valley of Costa Rica) are likely to be very distantly related, we do not need to study large families with many TS affected (or suspected TS affected) individuals. We can simply collect DNA from only those individuals in the population who have clear cut cases of TS and whose family history indicates that they are descended from that population’s founding members. We plan to examine the DNA of those affected individuals to see which portions they have in common. These shared DNA seg¬ments are assumed to be remnants of the original founders’TS¬carrying chromosome. By discovering the smallest DNA segments shared by the greatest number of the TS affected individuals, we will be able to narrow down the regions where TS susceptibility genes are likely to be, and then determine the sequence of these genes. Once the gene sequences are known, we will have a much greater understanding of the basic biology of TS, making it possible to design improved treatments. Mellissa M.C. DeMille, Ph.D. (Fellow) Nelson Freimer, M.D. (Sponsor) University of California, San Francisco, CA Award $30,018 Tourette Association of America Inc. – Research Grant Award 1996