Pathogenic mitochondrial DNA mutations are common in the general population

Hannah R Elliott, David C Samuels, James A Eden, Caroline L Relton, Patrick F Chinnery, Hannah R Elliott, David C Samuels, James A Eden, Caroline L Relton, Patrick F Chinnery

Abstract

Mitochondrial DNA (mtDNA) mutations are a major cause of genetic disease, but their prevalence in the general population is not known. We determined the frequency of ten mitochondrial point mutations in 3168 neonatal-cord-blood samples from sequential live births, analyzing matched maternal-blood samples to estimate the de novo mutation rate. mtDNA mutations were detected in 15 offspring (0.54%, 95% CI = 0.30-0.89%). Of these live births, 0.00107% (95% CI = 0.00087-0.0127) harbored a mutation not detected in the mother's blood, providing an estimate of the de novo mutation rate. The most common mutation was m.3243A-->G. m.14484T-->C was only found on sub-branches of mtDNA haplogroup J. In conclusion, at least one in 200 healthy humans harbors a pathogenic mtDNA mutation that potentially causes disease in the offspring of female carriers. The exclusive detection of m.14484T-->C on haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission.

Figures

Figure 1
Figure 1
Percentage of Mutated mtDNA in the 15 Mutation-Positive Cases Red: m.14484T→C; blue: m.11778G→A; green: m.3460G→A; black: m.3243A→G; orange: m.1555A→G.

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Source: PubMed

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