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Are Disease-Causing mtDNA Mutations Common?

image Genetic genealogy has the potential to reveal information about your health (for example, DYS464 can reveal infertility and sequencing of the entire mtDNA genome can reveal mutations that are suspected of being associated with certain disorders).  Although I usually don’t consider this possibility to be serious enough to discourage genetic genealogy testing, I do believe that people should be aware of the possibility before being tested.

A new study in the American Journal of Human Genetics (available here) examined the frequency of ten (potentially) pathogenic mitochondrial point mutations in 3168 neonatal cord blood samples.  Of these samples, a total of 15 (or 1 in 200) harbored one or more of the mutations.

Interestingly, the mtDNA of 12 of the 15 samples were heteroplasmic, meaning that their cells harbored both mutated and non-mutated mtDNA genomes.  Figure 1 from the paper, above, shows the percentage of mutated mtDNA in each of the 15 samples with mutations, from nearly 0% to the 100% in the three homoplasmic samples.

The 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-Con haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission.”

HT: Dienekes’ Anthropology Blog

Blaine Bettinger

Intellectual property attorney, genealogist, and author of The Genetic Genealogist since 2007

One Comment

  1. Studies of oncocytic tumours have led to hypotheses which propose that defects in oxidative phosphorylation may result in a compensatory increase in mitochondrial replication and/or gene expression. Mutational analysis of mtDNA in thyroid neoplasia, which is characterised by increased numbers of mitochondria and is also one of the most common sites of oncocytic tumours. has been limited to date. Using the recently developed technique of two-dimensional gene scanning, we have successfully examined 21 cases of thyroid tumours, six cases of non-neoplastic thyroid pathology, 30 population controls, nine foetal thyroid tissues and nine foetal tissues of non-thyroid origin, either kidney or liver.

    From: ncbi.nlm.nih.gov/pubmed/10803467

    domas’s last blog post..Traces of inflammation in the blood increase the possibility of Alzheimer’s disease

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