Name of Fellow

    Dr Gavin Hudson



    Parkinson's UK

    Contact information of fellow


    United Kingdom

    Title of project/programme

    The role of mitochondrial DNA variation in Parkinson's

    Source of funding information

    Parkinson's UK

    Total sum awarded (Euro)

    € 338,116

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders


    Molecular biology | Genetic studies | Biomarkers

    Research Abstract

    Mitochondria are intracellular organelles, whose function is critical to a number of metabolic processes. They are the site of oxidative phosphorylation; the protein components of which are partly encoded by mitochondrial DNA (mtDNA). Variation in mtDNA can affect the efficiency of oxidative phosphorylation. Increasing evidence links mitochondrial dysfunction to Parkinson’s disease (PD). PD patients have reduced respiratory chain function, specifically in the substantia nigra (SN), and inhibition of respiratory chain components has been shown to cause dopaminergic neuron loss in humans. Studies linking inherited mtDNA variants to PD have been inconclusive, reporting conflicting associations with common mtDNA haplogroups or with rare pathogenic variants. These studies were often underpowered, dependent on poorly defined haplogroup structures, and failed to link mtDNA variation to the somatic mutations well-described in the post mortem SN of PD patients. My hypothesis is that inherited and somatic mtDNA variation is intrinsically linked, combining to make a significant contribution to the multi-factorial aetiology of PD. I will test this hypothesis in two ways: 1) by defining the inherited variants at the whole mitochondrial genome level, and 2) correlating these findings with somatic mutation load in post mortem PD brains. I will utilise a large sample cohort and NGS to address the first point, subsequently addressing the second point by correlating risk conferring variants to somatic mtDNA mutations in post-mortem PD brains. I anticipate that these findings will identify a key component of the disease mechanism of PD, whilst explaining part of the ‘missing heritability’ of PD.

Types: Fellowships
Member States: United Kingdom
Diseases: Parkinson's disease & PD-related disorders
Years: 2016
Database Categories: N/A
Database Tags: N/A

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