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Targeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially Functional Variants in Tourette Syndrome Etiology.

ΤίτλοςTargeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially Functional Variants in Tourette Syndrome Etiology.
Publication TypeJournal Article
Year of Publication2016
AuthorsAlexander, J., Potamianou H., Xing J., Deng L., Karagiannidis I., Tsetsos F., Drineas P., Tarnok Z., Rizzo R., Wolanczyk T., Farkas L., Nagy P., Szymanska U., Androutsos C., Tsironi V., Koumoula A., Barta C., Sandor P., Barr C. L., Tischfield J., Paschou P., Heiman G. A., & Georgitsi M.
Corporate AuthorsTSGeneSEE
JournalFront Neurosci
Volume10
Pagination428
Date Published2016
ISSN1662-4548
Abstract

Although the genetic basis of Tourette Syndrome (TS) remains unclear, several candidate genes have been implicated. Using a set of 382 TS individuals of European ancestry we investigated four candidate genes for TS (, and ) in an effort to identify possibly causal variants using a targeted re-sequencing approach by next generation sequencing technology. Identification of possible disease causing variants under different modes of inheritance was performed using the algorithms implemented in VAAST. We prioritized variants using Variant ranker and validated five rare variants via Sanger sequencing in and , all of which are predicted to be deleterious. Intriguingly, one of the identified variants is in linkage disequilibrium with a variant that is included among the top hits of a genome-wide association study for response to citalopram treatment, an antidepressant drug with off-label use also in obsessive compulsive disorder. Our findings provide additional evidence for the implication of these two genes in TS susceptibility and the possible role of these proteins in the pathobiology of TS should be revisited.

DOI10.3389/fnins.2016.00428
Alternate JournalFront Neurosci
PubMed ID27708560
PubMed Central IDPMC5030307
Grant ListR01 MH092293 / MH / NIMH NIH HHS / United States
U24 MH068457 / MH / NIMH NIH HHS / United States

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