Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans.
Odhams, Christopher A
Taylor, Jenny C
Chinnery, Patrick F
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Wei, W., Pagnamenta, A. T., Gleadall, N., Sanchis-Juan, A., Stephens, J., Broxholme, J., Tuna, S., et al. (2020). Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans.. Nature communications, 11 (1)https://doi.org/10.1038/s41467-020-15336-3
Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down the maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report a similar genetic signature in 7 of 11,035 trios, with allelic fractions of 5-25%, implying biparental inheritance of mtDNA in 0.06% of offspring. However, analysing the nuclear whole genome sequence, we observe likely large rare or unique nuclear-mitochondrial DNA segments (mega-NUMTs) transmitted from the father in all 7 families. Independently detecting mega-NUMTs in 0.13% of fathers, we see autosomal transmission of the haplotype. Finally, we show the haplotype allele fraction can be explained by complex concatenated mtDNA-derived sequences rearranged within the nuclear genome. We conclude that rare cryptic mega-NUMTs can resemble paternally mtDNA heteroplasmy, but find no evidence of paternal transmission of mtDNA in humans.
External DOI: https://doi.org/10.1038/s41467-020-15336-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/305173
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/