Whole Exome Resequencing in Familial Tourette Syndrome

Grant Type
Basic
Grant Year
2010-2011
Institution Location
Foreign
Institution Organization Name
University of Montreal Canada
Investigators Name
Rouleau, Guy, MD, PhD

Tourette Syndrome (TS) is a complex neuropsychiatric disorder manifested particularly by motor and vocal tics and often associated with behavioural abnormalities (e.g. Obsessive Compulsive Disorder (OCD), Attention Deficit-Hyperactivity Disorder (ADHD), anxiety disorders, sleep disorders, depression, rage outbursts and oppositional defiant behavior). Various studies have confirmed the genetic basis of TS and concordance rates in twin studies suggest that TS may be caused by a mix of environmental and genetic factors. Parametric/non-parametric linkage studies have largely failed to identify replicable TS susceptibility loci using multi-affected large families. When considering genetic models for complex neuro-developmental diseases, there are only a few possibilities: rare penetrant recessive alleles, rare partly penetrant and more common less penetrant dominant alleles, and interactions between many genes. Genome re-sequencing promises to accelerate the identification of disease-associated mutations but about 98% of the human genome is composed of repeats and intergenic or non-protein-coding sequences. Thus, it is crucial to focus re-sequencing on high-value genomic regions. The protein-coding regions of the genome (the exome) represent such a high-value target. Exon-capture methods (e.g. Agilent Technology, SureSelect Human All Exon ki) coupled to next generation sequencing (e.g. ABI’s SOLiD) will allow us to re-sequence approximately 15,000 genes in each DNA sample. This new approach should significantly increase the probability of identifying disease-causing or susceptibility variants. Guy A. Rouleau, M.D., Ph.D. University of Montreal, Montreal, Canada Award: $75,000 Commentary: Tourette Syndrome (TS) is a complex and poorly treated disorder of the brain. Although genetic factors are known to play a role in TS and despite intensive research efforts, the identification of TS genes has had limited success. We propose to use modern and powerful techniques to examine approximately 15,000 genes in a group of ten individuals from five different TS families. Such a large-scale approach increases the probability of finding a gene associated with the disorder. Tourette Association of America Inc. – Research Grant Award 2010-2011