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Lookup NU author(s): Hannah O'Keefe, Dr Rachel Queen, Dr Phillip Lord, Dr Joanna Elson
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Mitochondrial diseases are a highly complex, heterogeneous group of disorders. Mitochondrial DNA variants that are linked to disease can exhibit variable expression and penetrance. This has an implication for mitochondrial diagnostics as variants that cause disease in one individual may not in another. It has been suggested that the sequence context in which a variant arises could influence the genotype–phenotype relationship. However, the consequence of sequence variation between different haplogroups on the expression of disease is not well understood. European haplogroups are the most widely studied. To ensure accurate diagnostics for patients globally, we first need to understand how, if at all, the sequence context in which a variant arises contributes to the manifestion of disease. To help us understand this, we used 2752 sequences from 33 non-human species that do not have disease. We searched for variants in the seven complex I genes that are associated with disease in humans. Our findings indicate that only three reported pathogenic complex I variants have arisen in these species. More importantly, only one of these, m.3308T>C, has arisen with its associated amino acid change in the studied non-human species. With the status of m.3308T>C as a disease causing variant being a matter of debate. This is a stark contrast to previous findings in the mitochondrial tRNA genes and suggests that sequence context may be less important in the complex I genes. This information will help us improve the identification and diagnosis of mitochondrial DNA variants in non-European populations.
Author(s): O'Keefe H, Queen RA, Meldau S, Lord P, Elson JL
Publication type: Article
Publication status: Published
Journal: Journal of Molecular Evolution
Year: 2018
Volume: 86
Issue: 6
Pages: 395-403
Print publication date: 01/07/2018
Online publication date: 09/07/2018
Acceptance date: 29/06/2018
Date deposited: 09/07/2018
ISSN (print): 0022-2844
ISSN (electronic): 1432-1432
Publisher: Springer New York LLC
URL: https://doi.org/10.1007/s00239-018-9855-7
DOI: 10.1007/s00239-018-9855-7
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