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Mildly deleterious mitochondrial DNA variants are less frequent in healthy older individuals, but not more prevalent in Alzheimer’s patients

Lookup NU author(s): Dr Ilse Pienaar, Dr Joanna Elson



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract Mitochondrial DNA (mtDNA) association studies have been conducted for over a decade using the haplogroup (lineage) association method, but this frequently produces conflicting results. Here we analyzed complete mtDNA sequence data of Alzheimer’s disease (AD) patients and aged controls, from the United Kingdom (UK) and the United States (US), using a new "mutational load” method. We calculated a pathogenicity score for each of the non-synonymous substitutions of the mtDNA sequences to produce a “total mutational load” for each sequence, and compared the mutational loads of cases and controls. Using these mutational load measures, we found no evidence to support the cumulative role of mtDNA variants as a susceptibility factor in AD; that is, AD patients (UK and US cohorts) did not have higher “mutational loads” than controls. However, the US aged controls, who are significantly older than the UK ones, with many showing evidence of being healthy and having good cognition in old age, had significantly lower “mutational loads”. This finding suggests that low mtDNA mutational load is more prevalent in healthy older people.

Publication metadata

Author(s): Pienaar IS, Howell N, Elson JL

Publication type: Article

Publication status: Published

Journal: Mitochondrion

Year: 2017

Volume: 34

Pages: 141-146

Print publication date: 01/05/2017

Online publication date: 07/04/2017

Acceptance date: 06/04/2017

Date deposited: 09/05/2017

ISSN (print): 1567-7249

ISSN (electronic): 1872-8278

Publisher: Elsevier


DOI: 10.1016/j.mito.2017.04.002


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