title: Targeted Re-Sequencing Approach of Candidate Genes Implicates Rare Potentially Functional Variants in Tourette Syndrome Etiology.
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 (HDC, SLITRK1, BTBD9, andSLC6A4) 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 inHDCandSLITRK1, 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.
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupoli, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Alexander
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupoli, Greece.
authors.forename: Hera
authors.initials: H
authors.lastname: Potamianou
authors.affiliation: Department of Genetics, Rutgers, The State University of New JerseyPiscataway, NJ, USA; Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyPiscataway, NJ, USA.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Genetics, Rutgers, The State University of New JerseyPiscataway, NJ, USA; Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyPiscataway, NJ, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupoli, Greece.
authors.forename: Iordanis
authors.initials: I
authors.lastname: Karagiannidis
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupoli, Greece.
authors.forename: Fotis
authors.initials: F
authors.lastname: Tsetsos
authors.affiliation: Computer Science Department, Purdue University West Lafayette, USA.
authors.forename: Petros
authors.initials: P
authors.lastname: Drineas
authors.affiliation: Vadaskert Clinic for Child and Adolescent Psychiatry Budapest, Hungary.
authors.forename: Zsanett
authors.initials: Z
authors.lastname: Tarnok
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania Catania, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Rizzo
authors.affiliation: Department of Child Psychiatry, Medical University of Warsaw Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wolanczyk
authors.affiliation: Vadaskert Clinic for Child and Adolescent Psychiatry Budapest, Hungary.
authors.forename: Luca
authors.initials: L
authors.lastname: Farkas
authors.affiliation: Vadaskert Clinic for Child and Adolescent Psychiatry Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Department of Child Psychiatry, Medical University of Warsaw Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Szymanska
authors.affiliation: Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Androutsos
authors.affiliation: Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica Athens, Greece.
authors.forename: Vaia
authors.initials: V
authors.lastname: Tsironi
authors.affiliation: Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Koumoula
authors.affiliation: Molecular Biology and Pathobiochemistry, Institute of Medical Chemistry, Semmelweis University Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Barta
authors.affiliation: Department of Psychiatry, University of Toronto Toronto, ON, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Sandor
authors.affiliation: Genetics and Development Division, Krembil Research Institute, University Health NetworkToronto, ON, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick ChildrenToronto, ON, Canada.
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Barr
authors.affiliation: Department of Genetics, Rutgers, The State University of New JerseyPiscataway, NJ, USA; Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyPiscataway, NJ, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace Alexandroupoli, Greece.
authors.forename: Peristera
authors.initials: P
authors.lastname: Paschou
authors.affiliation: Department of Genetics, Rutgers, The State University of New JerseyPiscataway, NJ, USA; Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyPiscataway, NJ, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Heiman
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of ThraceAlexandroupoli, Greece; Laboratory of General Biology, Department of Medicine, Aristotle University of ThessalonikiThessaloniki, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Georgitsi
keywords: HDC; SLITRK1; TS candidate genes; genetic susceptibility; next generation sequencing; rare variants; targeted re-sequencing