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Comparative Study
. 2004 Jan;25(1):71-81.
doi: 10.1016/s0197-4580(03)00037-x.

Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's disease

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Comparative Study

Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's disease

David K Simon et al. Neurobiol Aging. 2004 Jan.

Abstract

Oxidative damage to mitochondrial DNA (mtDNA) increases with age in the brain and can induce G:C to T:A and T:A to G:C point mutations. Though rare at any particular site, multiple somatic mtDNA mutations induced by oxidative damage or by other mechanisms may accumulate with age in the brain and thus could play a role in aging and neurodegenerative diseases. However, no prior study has quantified the total burden of mtDNA point mutation subtypes in the brain. Using a highly sensitive cloning and sequencing strategy, we find that the aggregate levels of G:C to T:A and T:A to G:C transversions and of all point mutations increase with age in the frontal cortex (FCtx). In the substantia nigra (SN), the aggregate levels of point mutations in young controls are similar to the levels in the SN or FCtx of elderly subjects. Extrapolation from our data suggests an average of 2.7 (FCtx) to 3.2 (SN) somatic point mutations per mitochondrial genome in elderly subjects. There were no significant differences between Parkinson's disease (PD) patients and age-matched controls in somatic mutation levels. These results indicate that individually rare mtDNA point mutations reach a high aggregate burden in FCtx and SN of elderly subjects.

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  • Response to Simon et al.
    Wei W, Keogh MJ, Ironside JW, Chinnery PF. Wei W, et al. Acta Neuropathol Commun. 2017 Apr 29;5(1):34. doi: 10.1186/s40478-017-0434-8. Acta Neuropathol Commun. 2017. PMID: 28454558 Free PMC article. No abstract available.

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