Fernández Santiago, RubénMerkel, AngelikaCastellano, GiancarloHeath, SimonRaya Chamorro, ÁngelTolosa, EduardoMartí Domènech, Ma. JosepConsiglio, AntonellaEzquerra Trabalón, Mario2020-10-272020-10-272019-07-231868-7075https://hdl.handle.net/2445/171541Background: Parkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons (DAn). Previously, we described the presence of DNA hyper- and hypo-methylation alterations in induced pluripotent stem cells (iPSC)-derived DAn from PD patients using the Illumina 450K array which prominently covers gene regulatory regions. Methods: To expand and contextualize previous findings, we performed the first whole-genome DNA bisulfite sequencing (WGBS) using iPSC-derived DAn from representative PD subjects: one sporadic PD (sPD) patient, one monogenic LRRK2-associated PD patient (L2PD), and one control. Results: At the whole-genome level, we detected global DNA hyper-methylation in the PD which was similarly spread across the genome in both sPD and L2PD and mostly affected intergenic regions. Conclusion: This study implements previous epigenetic knowledge in PD at a whole genome level providing the first comprehensive and unbiased CpG DNA methylation data using iPSC-derived DAn from PD patients. Our results indicate that DAn from monogenic or sporadic PD exhibit global DNA hyper-methylation changes. Findings from this exploratory study are to be validated in further studies analyzing other PD cell models and patient tissues.7 p.application/pdfengcc-by (c) Fernández Santiago, Rubén et al., 2019http://creativecommons.org/licenses/by/3.0/esMalaltia de ParkinsonADNMetilacióParkinson's diseaseDNAMethylationinfo:eu-repo/semantics/article6975332020-10-27info:eu-repo/semantics/openAccess31337434