Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans
Wei W., Pagnamenta AT., Gleadall N., Sanchis-Juan A., Stephens J., Broxholme J., Tuna S., Odhams CA., Ambrose JC., Baple EL., Bleda M., Boardman-Pretty F., Boissiere JM., Boustred CR., Caulfield MJ., Chan GC., Craig CEH., Daugherty LC., de Burca A., Devereau A., Elgar G., Foulger RE., Fowler T., Furió-Tarí P., Hackett JM., Halai D., Holman JE., Hubbard TJP., Jackson R., Kasperaviciute D., Kayikci M., Lahnstein L., Lawson K., Leigh SEA., Leong IUS., Lopez FJ., Maleady-Crowe F., Mason J., McDonagh EM., Moutsianas L., Mueller M., Murugaesu N., Need AC., Odhams CA., Patch C., Perez-Gil D., Polychronopoulos D., Pullinger J., Rahim T., Rendon A., Riesgo-Ferreiro P., Rogers T., Ryten M., Savage K., Sawant K., Scott RH., Siddiq A., Sieghart A., Smedley D., Smith KR., Sosinsky A., Spooner W., Stevens HE., Stuckey A., Sultana R., Thomas ERA., Thompson SR., Tregidgo C., Tucci A., Walsh E., Watters SA., Welland MJ., Williams E., Witkowska K., Wood SM., Zarowiecki M., Sanchis-Juan A., Stephens J., Tuna S., Turro E., Chinnery PF., Fratter C., Turro E., Caulfield MJ., Taylor JC., Rahman S., Chinnery PF.
AbstractSeveral 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.