Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patients
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- dc.contributor.author Spataro, Nino, 1984-ca
- dc.contributor.author Roca-Umbert Würth, Anaca
- dc.contributor.author Cervera-Carles, Lauraca
- dc.contributor.author Vallès, Mònicaca
- dc.contributor.author Anglada Busquets, Rogerca
- dc.contributor.author Pagonabarraga, Javierca
- dc.contributor.author Pascual Sedano, Bertaca
- dc.contributor.author Campolongo Perillo, Antòniaca
- dc.contributor.author Kulisevsky, Jaime J.ca
- dc.contributor.author Casals López, Ferranca
- dc.contributor.author Clarimón Echevarría, Jordica
- dc.contributor.author Bosch Fusté, Elenaca
- dc.date.accessioned 2017-06-20T12:05:36Z
- dc.date.available 2017-06-20T12:05:36Z
- dc.date.issued 2017
- dc.description.abstract Background: The analysis of coverage depth in next-generation sequencing data allows the detection of gene dose alterations. We explore the frequency of such structural events in a Spanish cohort of sporadic PD cases. Methods: Gene dose alterations were detected with the eXome-Hidden Markov Model (XHMM) software from depth of coverage in resequencing data available for 38 Mendelian and other risk PD loci in 394 individuals (249 cases and 145 controls) and subsequently validated by quantitative PCR. Results: We identified 10 PD patients with exon dosage alterations in PARK2, GBA-GBAP1, and DJ1. Additional functional variants, including 2 novel nonsense mutations (p.Arg1552Ter in LRRK2 and p.Trp90Ter in PINK1), were confirmed by Sanger sequencing. This combined approach disclosed the genetic cause of 12 PD cases. Conclusions: Gene dose alterations related to PD can be correctly identified from targeting resequencing data. This approach substantially improves the detection rate of cases with causal genetic alterations. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
- dc.description.sponsorship This work was supported by the Ministerio de Ciencia e Innovación, Spain (SAF2011-29239), Ministerio de Economía y Competitividad and Fondo Europeo de Desarollo Regional (FEDER) (SAF2012-35025 and SAF2015-68472-C2-2-R), and by the Direcció General de Recerca, Generalitat de Catalunya (2014SGR-866 and 2014SGR-0235).
- dc.format.mimetype application/pdfca
- dc.identifier.citation Spataro N, Roca-Umbert Würth A, Cervera-Carles L, Vallès M, Anglada Busquets R, Pagonabarraga J et al. Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patients. Movement Disorders. 2017;32(1):165-9. DOI: 10.1002/mds.26845
- dc.identifier.doi http://dx.doi.org/10.1002/mds.26845
- dc.identifier.issn 0885-3185
- dc.identifier.uri http://hdl.handle.net/10230/32384
- dc.language.iso eng
- dc.publisher Wileyca
- dc.relation.ispartof Movement Disorders. 2017;32(1):165-9
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29239
- dc.rights © 2016 International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Parkinson's disease
- dc.subject.keyword Next generation sequencing
- dc.subject.keyword Structural variants
- dc.subject.keyword XHMM software
- dc.title Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patientsca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion