Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans


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Authors
Pagnamenta, Alistair T.  ORCID logo  https://orcid.org/0000-0001-7334-0602
Gleadall, Nicholas 
Sanchis-Juan, Alba 
Stephens, Jonathan 
Abstract

Abstract: 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.

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Keywords
Article, /631/208/2156, /631/208/726/649, /631/208/726/2129, /45, /45/23, article
Journal Title
Nature Communications
Conference Name
Journal ISSN
2041-1723
Volume Title
11
Publisher
Nature Publishing Group UK