TS-EUROTRAIN - Projects

Investigation of the role of copy number variations (CNVs) as genetic susceptibility factors involved in pathogenesis of TS and co-morbidity disorders (WP1)

Objectives: The overall aim of the project is to identify genetic susceptibility factors involved in the pathogenesis of TS and co-morbidity disorders, through investigation of rare copy number variations (CNVs) in a unique cohort of 214 deeply-phenotyped Danish patients.

Fellow ESR2   
Host institution: Kennedy Center
Duration: 36 months    
Supervisor: Z. Tümer, KC; Co-supervisor: P. Paschou, DUTH; Associated partner: J. Scharf, MGH; Seconding Company: deCODE.

Tasks and methodology: We have deeply phenotyped 307 patients (from 293 families) with validated clinical and psychological tests, and obtained biological material from 214 patients. Interview of the families indicated more than one patient was affected with TS and/or OCD/ADHD in 77% of the families, underlining the role of hereditary factors in disease pathology. Taking autism as an example for complex neuropsychiatric disorders, we expect rare CNVs as important genetic susceptibility factors to TS and in a pilot project comprising 70 patients we identified a CNVs (including a single gene) in 3% of the cases using a high-resolution microarray platform, whichsuggests that this is a very promising in identifying genetic risk factors in TS. We will carry out the project as follows:

  • Task 1: Screening of the whole cohort with microarray.
  • Task 2: Identification of candidate loci through data analyses and verification of the CNVs using quantitative PCR.
  • Task 2: Secondment at deCODE in order to compare results to the deCODE CNV database and receive training in CNV analysis.
  • Task 3: Investigation of other patient cohorts in collaboration with DUTH, UU (DC Cath) and MGH, in order to identify the most statistically significant regions.
  • Task 4: Investigation of the most promising genes (expressed in candidate brain regions for TS) further through functional analyses (tissue expression studies with RT-PCR, protein expression studies, in situ hybridization studies using commercially available adult brain sections).

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