CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.
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 auti...
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oai:doaj.org-article:eafb2194ce3c4fd685929f44b9c672582021-11-18T07:52:20ZCNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.1932-620310.1371/journal.pone.0059061https://doaj.org/article/eafb2194ce3c4fd685929f44b9c672582013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533600/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Tourette 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 ∼400 kb 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.Abhishek NagElena G BochukovaBarbara KremeyerDesmond D CampbellHeike MullerAna V Valencia-DuarteJulio CardonaIsabel C RivasSandra C MesaMauricio CuartasJharley GarciaGabriel BedoyaWilliam CornejoLuis D HerreraRoxana RomeroEduardo FournierVictor I ReusThomas L LoweI Sadaf FarooqiTourette Syndrome Association International Consortium for GeneticsCarol A MathewsLauren M McGrathDongmei YuEd CookKai WangJeremiah M ScharfDavid L PaulsNelson B FreimerVincent PlagnolAndrés Ruiz-LinaresPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59061 (2013) |
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| collection |
DOAJ |
| language |
EN |
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| spellingShingle |
Medicine R Science Q Abhishek Nag Elena G Bochukova Barbara Kremeyer Desmond D Campbell Heike Muller Ana V Valencia-Duarte Julio Cardona Isabel C Rivas Sandra C Mesa Mauricio Cuartas Jharley Garcia Gabriel Bedoya William Cornejo Luis D Herrera Roxana Romero Eduardo Fournier Victor I Reus Thomas L Lowe I Sadaf Farooqi Tourette Syndrome Association International Consortium for Genetics Carol A Mathews Lauren M McGrath Dongmei Yu Ed Cook Kai Wang Jeremiah M Scharf David L Pauls Nelson B Freimer Vincent Plagnol Andrés Ruiz-Linares CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. |
| description |
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 ∼400 kb 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. |
| format |
article |
| author |
Abhishek Nag Elena G Bochukova Barbara Kremeyer Desmond D Campbell Heike Muller Ana V Valencia-Duarte Julio Cardona Isabel C Rivas Sandra C Mesa Mauricio Cuartas Jharley Garcia Gabriel Bedoya William Cornejo Luis D Herrera Roxana Romero Eduardo Fournier Victor I Reus Thomas L Lowe I Sadaf Farooqi Tourette Syndrome Association International Consortium for Genetics Carol A Mathews Lauren M McGrath Dongmei Yu Ed Cook Kai Wang Jeremiah M Scharf David L Pauls Nelson B Freimer Vincent Plagnol Andrés Ruiz-Linares |
| author_facet |
Abhishek Nag Elena G Bochukova Barbara Kremeyer Desmond D Campbell Heike Muller Ana V Valencia-Duarte Julio Cardona Isabel C Rivas Sandra C Mesa Mauricio Cuartas Jharley Garcia Gabriel Bedoya William Cornejo Luis D Herrera Roxana Romero Eduardo Fournier Victor I Reus Thomas L Lowe I Sadaf Farooqi Tourette Syndrome Association International Consortium for Genetics Carol A Mathews Lauren M McGrath Dongmei Yu Ed Cook Kai Wang Jeremiah M Scharf David L Pauls Nelson B Freimer Vincent Plagnol Andrés Ruiz-Linares |
| author_sort |
Abhishek Nag |
| title |
CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. |
| title_short |
CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. |
| title_full |
CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. |
| title_fullStr |
CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. |
| title_full_unstemmed |
CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. |
| title_sort |
cnv analysis in tourette syndrome implicates large genomic rearrangements in col8a1 and nrxn1. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/eafb2194ce3c4fd685929f44b9c67258 |
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