Nanopore single-molecule sequencing to investigate mitochondrial DNA CpG methylation in Parkinson’s disease

Theresa Lüth

Theresa Lüth, University of Lübeck, Germany


Mitochondrial dysfunction is a key player in Parkinson’s disease (PD) pathogenesis. However, the mitochondrial epigenome and its implication in disease remains unexplored, due to contradictory reports about its biological relevance and methodological limitations. We performed whole-genome nanopore sequencing of native DNA derived from blood and -derived midbrain neurons from patients with PD and healthy control subjects. CpG methylation was detected using Nanopolish and Megalodon. Our preliminary results show that mtDNA CpG methylation is low, with variability across cell types. We observe lower mtDNA methylation levels in neurons and lower methylation in PD patients compared to healthy controls


Theresa Lüth has completed her Master’s degree at the Institute of Neurogenetics, University of Lübeck in 2020 under the supervision of Dr. Joanne Trinh. During this period, she explored the application of different nanopore sequencing workflows, including mitochondrial DNA (mtDNA) methylation, repeat expansions, and microbiome analysis. In 2021, she continued her genetic research as a Ph.D. student in the same group (Integrative Omics Approaches in Parkinson’s Disease) to investigate (epi-) genetic and environmental modifiers of monogenic Parkinson’s disease.