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The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease

Lookup NU author(s): Dr Jim StewartORCiD, Professor Patrick Chinnery


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Common genetic variants of mitochondrial DNA (mtDNA) increase the risk of developing several of the major health issues facing the western world, including neurodegenerative diseases. In this Review, we consider how these mtDNA variants arose and how they spread from their origin on one single molecule in a single cell to be present at high levels throughout a specific organ and, ultimately, to contribute to the population risk of common age-related disorders. mtDNA persists in all aerobic eukaryotes, despite a high substitution rate, clonal propagation and little evidence of recombination. Recent studies have found that de novo mtDNA mutations are suppressed in the female germ line; despite this, mtDNA heteroplasmy is remarkably common. The demonstration of a mammalian mtDNA genetic bottleneck explains how new germline variants can increase to high levels within a generation, and the ultimate fixation of less-severe mutations that escape germline selection explains how they can contribute to the risk of late-onset disorders.

Publication metadata

Author(s): Stewart JB, Chinnery PF

Publication type: Review

Publication status: Published

Journal: Nature Reviews Genetics

Year: 2015

Volume: 16

Issue: 9

Pages: 530-542

Print publication date: 01/09/2015

Online publication date: 18/08/2015

Acceptance date: 01/01/1900

ISSN (print): 1471-0056

ISSN (electronic): 1471-0064



DOI: 10.1038/nrg3966