Tourette Syndrome (TS) is a developmental neuropsychiatric disorder that is highly heritable, though it has been difficult to identify unequivocal TS susceptibility genes to date. One striking feature of TS is the existence of many extended pedigrees each containing multiple affected individuals with either TS or its broader, genetically related phenotype, chronic tics (CT). The Tourette Syndrome Association International Consortium for Genetics (TSAICG) has spent over a decade investigating 15 such multi-generational families (more than 750 individuals including 213 affected with TS/CT across multiple generations), and has identified a TS/CT susceptibility locus with genome-wide significant linkage on chromosome 2p. The goal of this XO1 application to the Center for Inherited Disease Research (CIDR) is to utilize exon-focused sequencing methods, including targeted capture of the chromosome 2p linkage region, as well as whole exome sequencing, to identify causal TS risk gene variants of moderate-to-large effect in these families. This proposal provides a unique and exciting opportunity to rapidly advance the goal of elucidating the biological basis of this complex and important model neuropsychiatric disorder. By combining whole-exome sequencing with additional, dense targeted sequencing of functional elements within a confirmed linkage region, we have the opportunity to gain insight into the full genetic landscape of a complex disease in individual families.

Public Health Relevance

This research aims to use next-generation DNA sequencing to discover Tourette Syndrome (TS) susceptibility genes in large families where TS is present in multiple family members. Discovery of TS genes would provide important insight into the underlying cause(s) of this disorder and could lay the groundwork for improved diagnosis and treatment of this condition. The preliminary written comments of the reviewers are reproduced below. These comments were prepared prior to the meeting and may not have been edited after the full committee discussion of your application.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research and Development Contracts (N01)
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Johns Hopkins University
United States
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