Our genomics laboratory has pioneered a novel approach to studying disease of the nervous system by examining changes of gene expression in white cells in the blood. After drawing a blood sample, RNA is isolated and applied to microarrays that make it possible to examine virtually all types of RNA present in the blood. Because active genes produce RNA, we can use the RNA profile as an indicator of gene expression. Using this approach we have previously shown that there are unique profiles of gene expression in children and adults with Down syndrome, Neurofibromatosis and Tuberous Sclerosis—all diseases that affect the brain. In a preliminary study done in collaboration with Donald Gilbert M.D., at the University of Cincinnati we showed differences of gene expression in the blood of children and teenagers with familial Tourette Syndrome (TS). In this subgroup, genes from Natural Killer (NK) cells and CD8+ cells were consistently over-expressed while in other TS patients and control (unaffected) patients they were not. Though the significance of these findings is still uncertain, the results may reflect differences in genetics, immune status or exposure to environmental factors such as group A beta hemolytic streptococcus within the TS population. The first aim of the study is to determine whether blood genomic profiles of familial TS patients are indeed significantly different from unaffected people of the same age, gender and race, and whether a subgroup of familial TS patients express NK and CD8+ cell genes at higher levels than other familial TS patients and people without TS. The second aim of the study is to confirm these findings using a quantitative technique called RT-PCR. We hypothesize that blood genomic profiles of patients with familial TS will differ from patients who do not have TS, and at least one subgroup of familial TS patients will be identified on the basis of NK/CD8 cell gene expression. Such subgrouping will help future studies to determine whether these patients have a particular genetic predisposition to TS, or whether these patients have a particular predisposition to streptococcal infections that could either cause, contribute to, or exacerbate TS symptoms. Frank R. Sharp, M.D. University of California at Davis, Sacramento, California Award: $75,000 This award is funded through the generosity of Constantine Scrivanos Tourette Association of America Inc. – Research Grant Award 2006-2007