August 04, 2008

Pathogenic mtDNA is common

A piece of evidence which suggests lineage-specific negative selection in human mtdna.

The American Journal of Human Genetics, doi:10.1016/j.ajhg.2008.07.004

Pathogenic Mitochondrial DNA Mutations Are Common in the General Population

Hannah R. Elliott et al.


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 = 0.300.89%). Of these live births, 0.00107% (95% CI = 0.000870.0127) 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.3243AG. m.14484TC 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.14484TCon haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission.



Maju said...

I am under the strong impression that all pathogenic mtDNA mutations are in the branches leading to recent sublineages, that there are no upstream shared pathogenic mutations left at all. This would mean that all or most of the pathogenic lineages are bound to become extinct sooner or later, and that the same has happened in the past.

Anyone disagreeing?

hurrayforsarasota said...

There have been comments on other forums indicting U5 with a tendency toward migraine headaches.

The Other Jim said...


My understanding is that 9 of the 10 mutations appeared in multiple haplogroups. The best explanation for this is multiple, independent occurrences of the same mutation. The paper also cites work to show the 10th mutation only occurs in one haplogroup, but haplogroup J may predispose the occurrence of that mutation.

If they are appearing independently, they may disappear in these lineages, but may appear again elsewhere...