2024-03-29T14:55:28Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1505932021-12-28T15:34:38Zcom_10261_9676com_10261_8col_10261_9677
Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patients
Spataro, Nino
Roca-Umbert, Ana
Valles, Mònica
Bosch, Elena
Ministerio de Ciencia e Innovación (España)
Ministerio de Economía y Competitividad (España)
Generalitat de Catalunya
Spataro, Nino et al.-- Special Series: Advances in Functional Neurosurgery for Parkinson's Disease and Movement Disorders.
[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.
2017-05-29T12:35:32Z
2017-05-29T12:35:32Z
2017-01
artículo
Movement Disorders 32: 165-169 (2017)
0885-3185
http://hdl.handle.net/10261/150593
10.1002/mds.26845
1531-8257
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100002809
28124432
eng
Publisher's version
http://dx.doi.org/10.1002/mds.26845
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68472-C2-2-R
http://creativecommons.org/licenses/by/4.0/
openAccess
John Wiley & Sons