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


Type
Article
Change log
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
Journal Title
Nature communications
Conference Name
Journal ISSN
2041-1723
Volume Title
11
Publisher