TY - JOUR
T1 - Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patients
AU - Spataro, Nino
AU - Roca-Umbert, Ana
AU - Cervera-Carles, Laura
AU - Vallès, Mònica
AU - Anglada, Roger
AU - Pagonabarraga, Javier
AU - Pascual-Sedano, Berta
AU - Campolongo, Antònia
AU - Kulisevsky, Jaime
AU - Casals, Ferran
AU - Clarimón, Jordi
AU - Bosch, Elena
PY - 2017/1/1
Y1 - 2017/1/1
N2 - © 2016 International Parkinson and Movement Disorder Society 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.
AB - © 2016 International Parkinson and Movement Disorder Society 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.
KW - Parkinson's disease
KW - XHMM software
KW - next generation sequencing
KW - structural variants
U2 - https://doi.org/10.1002/mds.26845
DO - https://doi.org/10.1002/mds.26845
M3 - Article
VL - 32
SP - 165
EP - 169
IS - 1
ER -