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DNA study may have implications for mitochondrial donation

3 June 2019
Appeared in BioNews 1000

Mitochondria are not as interchangeable as originally thought, which may have implications for the selection of donors for mitochondrial donation

The DNA in mitochondria appears to interact with nuclear DNA in a way that suggests they are more closely aligned than previously thought, according to a study in the journal Science

'This discovery shows us that there's a subtle relationship between the mitochondria and nuclei in our cells that we're only just starting to understand,' said senior author Professor Patrick Chinnery at the University of Cambridge. 'What this suggests to us is that swapping mitochondria might not be as straightforward as just changing the batteries in a device.'

While most of our DNA is situated in the nuclei of our cells, a very small proportion sits within our mitochondria and this is inherited only from our mother. Harmful mutations in mitochondrial DNA can cause severe mitochondrial diseases, which are often fatal.

Mitochondrial donation was developed as a treatment to allow families affected by severe mitochondrial DNA mutations the opportunity to have a healthy genetically-related child. The technique involves substituting nuclear DNA from the mother's egg into a donor egg, which contains the donor's mitochondria. 

In this study, the researchers compared mitochondrial and nuclear DNA of over 1500 mother-child pairs from the UK-wide 100,000 Genomes Project. They found that in 45 percent of these pairs there were mutations affecting at least one percent of their mitochondrial DNA. Changes in mitochondrial DNA appeared to be linked to differences in the nuclear DNA. 

'Our work suggests we'll need to look carefully at [mitochondrial donation] to make sure it does not cause unexpected health problems further down the line,' said Professor Chinnery. 'It may mean that doctors will need to match the nuclear genome and mitochondrial genome of mitochondrial donors, similar to an organ transplant.'

The researchers are now looking to research cases where someone's mitochondrial DNA does not match their nuclear DNA, to see if this mismatch makes them more prone to health problems.

'We do not know if this could lead to health implications in the adult,' said Dr David Clancy at Lancaster University, who was not involved in the study. 'As a precaution, matching of donor and recipient genomes should now be made routine for this procedure.'

SOURCES & REFERENCES
DNA discovery could have implications for mitochondrial donation treatment
Queen Mary University of London |  23 May 2019
Germline selection shapes human mitochondrial DNA diversity
Science |  24 May 2019
Interplay between mitochondria and the nucleus may have implications for changing cell’s ‘batteries’
University of Cambridge |  23 May 2019
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