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CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1.

Nag, A; Bochukova, EG; Kremeyer, B; Campbell, DD; Muller, H; Valencia-Duarte, AV; Cardona, J; ... Ruiz-Linares, A; + view all (2013) CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1. PLoS One , 8 (3) , Article e59061. 10.1371/journal.pone.0059061. Green open access

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Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

Type: Article
Title: CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0059061
Publisher version: http://dx.doi.org/10.1371/journal.pone.0059061
Language: English
Additional information: © 2013 Nag et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by National Institutes of Health (http://www.nih.gov/) grants NS043538 (to ARL), NS037484 (to NBF), MH085057 (to JMS), NS40024 (to DLP and JMS) and NS16648 (the Tourette Syndrome Association International Consortium for Genetics), a CODI grant (http://www.udea.edu.co/portal/page/porta​l/Programas/GruposInvestigacion/h.Convoc​atorias/CODI/estrategiaSostenibilidad) (Sostenibilidad, Universidad de Antioquia), a grant from the Judah Foundation (http://www.judahfoundation.org/), and the Tourette Syndrome Association (http://tsa-usa.org/) (fellowship to BK and a grant to DLP). VP is supported by a grant from the United Kingdom Medical Research Council (http://www.mrc.ac.uk) (G1001158) and by the NIHR Moorfields Biomedical Research Council (http://www.brcophthalmology.org/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/1389458
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