Role of Common Chromosomal Rearrangements in Tourette Syndrome Etiology

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of California
Investigators Name
Keen-Kim, Dianne, PhD

Several complex neurologic diseases with genetics similar to Tourette Syndrome (TS) (e.g. multiple sclerosis, autism, and panic disorder) have recently been linked to DNA sequences that predispose very small rearrangements in patient chromosomal material. These sequences, called segmental duplications (SDs), can mediate deletions, duplications, and inversions in the DNA, thereby altering gene expression and producing consistent clinical consequences. We have analyzed regions of the human genome recently linked to TS by the TSA International Consortium on Genetics, and identified clusters of SDs within the most statistically significant genomic regions. The relative abundance of SDs throughout the genome and their participation in complex disease suggests that they may play a role in TS genetics. The purpose of this study is to characterize SDmediated genomic rearrangements in the loci with suggestive linkage to TS. Cytogenetic methods, including comparative genomic hybridization and fluorescent in situ hybridization will be used to determine the patterns of rearrangements in affected and unaffected individuals. We will then correlate DNA rearrangements with TS status to define the role genomic architecture plays in TS. Identification of genetic factors responsible for TS will provide insights into the causes of TS, open doors for its treatment and diagnosis, and serve as an example for other gene mapping studies that target complex and neurological disease. Dianne Keen-Kim, Ph.D. University of California, Los Angeles, California Award: $40,000 This Award is Funded Through The Generosity of The Ochsman Family Foundation Tourette Association of America Inc. – Research Grant Award 2005-2006