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Approved research

The prevalence of nuclear/mitochondrial DNA interactions in the UK population.

Principal Investigator: Dr Gavin Hudson
Approved Research ID: 40038
Approval date: November 14th 2018

Lay summary

Mitochondria are present in almost every human cell, producing the energy needed for our cells to function. Unlike our chromosomal DNA (nDNA), which is arranged in pairs of chromosomes (inheriting one set from our father and one from our mother), mitochondria contain their own DNA, known as mtDNA, which is inherited solely from our mothers. Just as mutations in nDNA can cause disease, mutations in our mtDNA can also cause disease. As mitochondria are ubiquitous across our cell types and because they have such a pivotal role in supplying our cellular energy, it is unsurprising that mitochondrial dysfunction (typically a loss of cellular energy) causes a broad range of human disease. Mitochondrial disease can be present at birth or develop later in life and causes debilitating physical, developmental, and cognitive disabilities with symptoms including poor growth; loss of muscle coordination; muscle weakness and pain; seizures; vision and/or hearing loss; gastrointestinal issues; learning disabilities; and organ failure. The severity of mitochondrial disease has led to recent work, pioneered at Newcastle University, which is aimed at eradicating mitochondrial disease completely by using IVF technique known as Mitochondrial Replacement Therapy (MRT). MRT aims to stop the transmission of mitochondrial disease from mother to child. In its simplest terms, the technique involves replacing the unhealthy mitochondria (and therefore the mutant mtDNA) in a woman who carries the disease, with the healthy mitochondria from a donor woman, during IVF. The resulting baby would, therefore, have mtDNA from a 3rd person (<0.1%), but the nDNA (>99.9%) from their mother and father. However, the use of MRT has raised some interesting questions. Recent research has suggested that replacing a mother's mitochondria with the mitochondria from a random donor may lead to incompatibilities within the cell, resulting in cellular dysfunction and thus rendering the technique useless. This makes the assumption that there is a pre-existing relationship between a mother's nDNA and mtDNA, which is broken by MRT. However, if as expected there are no strong nDNA/mtDNA relationships in the population, then MRT would be a viable treatment for mitochondrial disease. We wish to use the nDNA and mtDNA genetic information available in the UKBiobank to test for these relationships in the population. The UKBioBank also has a wealth of individual information. If we find any nDNA/mtDNA relationships we will correlate them to specific phenotype data within the UKBioBank to assess the potential functional role of ay nDNA/mtDNA relationships.