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

Accepted version
Peer-reviewed

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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

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.

Description

Keywords

Cell Nucleus, DNA, Mitochondrial, Family, Female, Haplotypes, Humans, Male, Models, Genetic, Paternal Inheritance, Pedigree, Reproducibility of Results

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (212219/Z/18/Z)
Medical Research Council (MC_PC_14089)
Medical Research Council (MC_UU_00015/7)