title: Detection of genomic rearrangements from targeted resequencing data in Parkinson's disease patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Nino
authors.initials: N
authors.lastname: Spataro
authors.affiliation: Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Roca-Umbert
authors.affiliation: Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Cervera-Carles
authors.affiliation: Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Vallès
authors.affiliation: Genomics Core Facility, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Anglada
authors.affiliation: Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pagonabarraga
authors.affiliation: Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.|Health Sciences Department, Universitat Oberta de Catalunya, Catalonia, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Pascual-Sedano
authors.affiliation: Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.|Health Sciences Department, Universitat Oberta de Catalunya, Catalonia, Spain.
authors.forename: Antònia
authors.initials: A
authors.lastname: Campolongo
authors.affiliation: Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.|Health Sciences Department, Universitat Oberta de Catalunya, Catalonia, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Kulisevsky
authors.affiliation: Genomics Core Facility, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Casals
authors.affiliation: Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau-Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.|Center for Networking Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.affiliation: Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Elena
authors.identifier: 0000-0003-2848-103X
authors.initials: E
authors.lastname: Bosch
mesh_terms: D015331:Cohort Studies; D056915:DNA Copy Number Variations; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D013030:Spain
keywords: Parkinson's disease; XHMM software; next generation sequencing; structural variants