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Lookup NU author(s): Dr Wei Wei, Dr Aurora Gomez Duran, Professor Gavin Hudson, Professor Patrick Chinnery
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 Wei et al. Inherited mitochondrial DNA (mtDNA) mutations have emerged as a common cause of human disease, with mutations occurring multiple times in the world population. The clinical presentation of three pathogenic mtDNA mutations is strongly associated with a background mtDNA haplogroup, but it is not clear whether this is limited to a handful of examples or is a more general phenomenon. To address this, we determined the characteristics of 30,506 mtDNA sequences sampled globally. After performing several quality control steps, we ascribed an established pathogenicity score to the major alleles for each sequence. The mean pathogenicity score for known disease-causing mutations was significantly different between mtDNA macro-haplogroups. Several mutations were observed across all haplogroup backgrounds, whereas others were only observed on specific clades. In some instances this reflected a founder effect, but in others, the mutation recurred but only within the same phylogenetic cluster. Sequence diversity estimates showed that disease-causing mutations were more frequent on young sequences, and genomes with two or more disease-causing mutations were more common than expected by chance. These findings implicate the mtDNA background more generally in recurrent mutation events that have been purified through natural selection in older populations. This provides an explanation for the low frequency of mtDNA disease reported in specific ethnic groups.
Author(s): Wei W, Gomez-Duran A, Hudson G, Chinnery PF
Publication type: Article
Publication status: Published
Journal: PLoS Genetics
Year: 2017
Volume: 13
Issue: 12
Print publication date: 31/12/2017
Online publication date: 18/12/2017
Acceptance date: 26/11/2017
Date deposited: 16/01/2018
ISSN (print): 1553-7390
ISSN (electronic): 1553-7404
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.pgen.1007126
DOI: 10.1371/journal.pgen.1007126
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