Mitochondrial Methylation Two-Peak Profile Absent in Parkinson’s Disease Patient

Abstract

ABSTRACTWhole-mitochondrial genome methylation profiles were obtained for mitochondrial DNA (mtDNA) from blood samples of one sporadic Parkinson’s Disease (PD) patient and one healthy control donor, via Whole-Genome Next-Generation Bisulfite Sequencing. Methylation frequency was determined at 836 CpG sites out of the 1146 CpG sites in mtDNA (73% of the total). The control mtDNA methylation profile exhibited a two-peak frequency distribution, with most CpG sites showing either no methylation, or a methylation above 7%. Instead, the sporadic PD mtDNA methylation profile exhibited a generic bell-shaped frequency distribution. The data is suggestive of the bell-shaped methylation profile arising via a degradation towards randomness of the healthy sample two-peak methylation pattern. Overall, this finding provides a possible explanation for the repeated observation of PD-phenotypic characteristics in cybrid cell lines where solely the mtDNA originates from a PD patient. We discuss the finding in terms of the sporadic PD Hematopoietic Origin Theory (HOT).