Open AccessMolecular characterization of PRKN structural variations identified through whole‐genome sequencing
Author(s) -
Bravo Paloma,
Darvish Hossein,
Tafakhori Abbas,
Azcona Luis J.,
Johari Amir Hossein,
Jamali Faezeh,
PaisánRuiz Coro
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.482
Subject(s) - sanger sequencing , genetics , whole genome sequencing , biology , exon , gene , genome , dna sequencing , computational biology
Background Early‐onset Parkinson's disease (PD) is the most common inherited form of parkinsonism, with the PRKN gene being the most frequently identified mutated. Exon rearrangements, identified in about 43.2% of the reported PD patients and with higher frequency in specific ethnicities, are the most prevalent PRKN mutations reported to date in PD patients. Methods In this study, three consanguineous families with early‐onset PD were subjected to whole‐genome sequencing (WGS) analyses that were followed by Sanger sequencing and droplet digital PCR to validate and confirm the disease segregation of the identified genomic variations and to determine their parental origin. Results Five different PRKN structural variations (SVs) were identified. Because the genomic sequences surrounding the break points of the identified SVs might hold important information about their genesis, these were also characterized for the presence of homology and repeated sequences. Conclusion We concluded that all identified PRKN SVs might originate through retrotransposition events.