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Review
. 2018 Oct 12:12:682.
doi: 10.3389/fnins.2018.00682. eCollection 2018.

Oldies but Goldies mtDNA Population Variants and Neurodegenerative Diseases

Patrick F Chinnery  1   2 , Aurora Gomez-Duran  1   2
Affiliations
Review

Oldies but Goldies mtDNA Population Variants and Neurodegenerative Diseases

Patrick F Chinnery et al. Front Neurosci. .

Abstract

mtDNA is transmitted through the maternal line and its sequence variability, which is population specific, is assumed to be phenotypically neutral. However, several studies have shown associations between the variants defining some genetic backgrounds and the susceptibility to several pathogenic phenotypes, including neurodegenerative diseases. Many of these studies have found that some of these variants impact many of these phenotypes, including the ones defining the Caucasian haplogroups H, J, and Uk, while others, such as the ones defining the T haplogroup, have phenotype specific associations. In this review, we will focus on those that have shown a pleiotropic effect in population studies in neurological diseases. We will also explore their bioenergetic and genomic characteristics in order to provide an insight into the role of these variants in disease. Given the importance of mitochondrial population variants in neurodegenerative diseases a deeper analysis of their effects might unravel new mechanisms of disease and help design new strategies for successful treatments.

Keywords: LHON; PD; haplogroups; mtDNA; neurodegenerative diseases.

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Figures

FIGURE 1
FIGURE 1
mtDNA inheritance. mtDNA haplogroups. mtDNA is shown as a orange circle, mtDNA variants with little circles in colors.
FIGURE 2
FIGURE 2
mtDNA phylogenetic tree. This tree shows the age (YBP) of different mtDNA haplogroups. The major Caucasian haplogroups H, U, and J are highlighted in yellow, blue, and red, respectively. Sub-haplogroups which has shown pleiotropic effect in neurodegenerative diseases are highlighted with green circles.
FIGURE 3
FIGURE 3
Transmitochondrial cybrid model. Construction of cybrid cell lines containing the same nuclear DNA, but mtDNA from healthy individuals with different mtDNA haplogroups. The oval circles inside the cell with colors white, gray, blue, pink and black represent no mtDNA and mtDNA from with different mtDNA, respectively.
See this image and copyright information in PMC

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