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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606459/ https://www.ncbi.nlm.nih.gov/pubmed/23533600 http://dx.doi.org/10.1371/journal.pone.0059061 |
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author | Nag, Abhishek Bochukova, Elena G. Kremeyer, Barbara Campbell, Desmond D. Muller, Heike Valencia-Duarte, Ana V. Cardona, Julio Rivas, Isabel C. Mesa, Sandra C. Cuartas, Mauricio Garcia, Jharley Bedoya, Gabriel Cornejo, William Herrera, Luis D. Romero, Roxana Fournier, Eduardo Reus, Victor I. Lowe, Thomas L. Farooqi, I. Sadaf Mathews, Carol A. McGrath, Lauren M. Yu, Dongmei Cook, Ed Wang, Kai Scharf, Jeremiah M. Pauls, David L. Freimer, Nelson B. Plagnol, Vincent Ruiz-Linares, Andrés |
author_facet | Nag, Abhishek Bochukova, Elena G. Kremeyer, Barbara Campbell, Desmond D. Muller, Heike Valencia-Duarte, Ana V. Cardona, Julio Rivas, Isabel C. Mesa, Sandra C. Cuartas, Mauricio Garcia, Jharley Bedoya, Gabriel Cornejo, William Herrera, Luis D. Romero, Roxana Fournier, Eduardo Reus, Victor I. Lowe, Thomas L. Farooqi, I. Sadaf Mathews, Carol A. McGrath, Lauren M. Yu, Dongmei Cook, Ed Wang, Kai Scharf, Jeremiah M. Pauls, David L. Freimer, Nelson B. Plagnol, Vincent Ruiz-Linares, Andrés |
author_sort | Nag, Abhishek |
collection | PubMed |
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 ∼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. |
format | Online Article Text |
id | pubmed-3606459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36064592013-03-26 CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1 Nag, Abhishek Bochukova, Elena G. Kremeyer, Barbara Campbell, Desmond D. Muller, Heike Valencia-Duarte, Ana V. Cardona, Julio Rivas, Isabel C. Mesa, Sandra C. Cuartas, Mauricio Garcia, Jharley Bedoya, Gabriel Cornejo, William Herrera, Luis D. Romero, Roxana Fournier, Eduardo Reus, Victor I. Lowe, Thomas L. Farooqi, I. Sadaf Mathews, Carol A. McGrath, Lauren M. Yu, Dongmei Cook, Ed Wang, Kai Scharf, Jeremiah M. Pauls, David L. Freimer, Nelson B. Plagnol, Vincent Ruiz-Linares, Andrés PLoS One Research Article 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. Public Library of Science 2013-03-22 /pmc/articles/PMC3606459/ /pubmed/23533600 http://dx.doi.org/10.1371/journal.pone.0059061 Text en © 2013 Nag et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Nag, Abhishek Bochukova, Elena G. Kremeyer, Barbara Campbell, Desmond D. Muller, Heike Valencia-Duarte, Ana V. Cardona, Julio Rivas, Isabel C. Mesa, Sandra C. Cuartas, Mauricio Garcia, Jharley Bedoya, Gabriel Cornejo, William Herrera, Luis D. Romero, Roxana Fournier, Eduardo Reus, Victor I. Lowe, Thomas L. Farooqi, I. Sadaf Mathews, Carol A. McGrath, Lauren M. Yu, Dongmei Cook, Ed Wang, Kai Scharf, Jeremiah M. Pauls, David L. Freimer, Nelson B. Plagnol, Vincent Ruiz-Linares, Andrés CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1 |
title | CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1
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title_full | CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1
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title_fullStr | CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1
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title_full_unstemmed | CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1
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title_short | CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1
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title_sort | cnv analysis in tourette syndrome implicates large genomic rearrangements in col8a1 and nrxn1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606459/ https://www.ncbi.nlm.nih.gov/pubmed/23533600 http://dx.doi.org/10.1371/journal.pone.0059061 |
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