Role of Common Chromosomal Rearrangements in Tourette Syndrome Etiology (2nd year)

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

Several complex neurologic diseases (e.g. multiple sclerosis, autism, and panic disorder) have recently been linked to DNA sequences that predispose small genomic rearrangements in the patient’s chromosomal material. These sequences, called segmental duplications (SDs), can mediate deletions, duplications, and inversions in the DNA, thereby altering gene expression and producing clinical consequences. Submicroscopic copy number polymorphisms (CNPs) are extremely common within the human genome and are predicted to have a major impact on human variation, especially for complex conditions such as TS. The purpose of this study is to characterize and catalogue the CNPs in TS-affected sibling pairs and their parents in samples collected by the Tourette Syndrome Association International Consortium on Genetics (TSAICG). Observed genomic rearrangements will be correlated with TS status. These experiments continue from work begun in the 2005-2006 TSA grant period, and use array comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH)—techniques demonstrated to be the most successful and efficient for studying submicroscopic genomic variation. Results will be used to determine whether CNPs are responsible for altering gene expression patterns and contribute to TS etiology. Findings may also be useful to the TSAICG in recording the different types and frequencies of genomic variation that may affect genetic linkage results. Identification of genetic factors responsible for TS will provide insights into the causes of TS, open doors for better treatments and diagnoses, and serve as an example for other gene mapping studies that target complex neurological diseases. Jennifer Dianne Keen-Kim, Ph.D. University of California, Los Angeles, California Award: $40,000 (2nd Year) Tourette Association of America Inc. – Research Grant Award 2006-2007