Biparental Inheritance of Mitochondrial DNA in Humans.
Level 4 - case-series / case-control
Genetic pedigree case series in humans (3 multigenerational families)
PubMed 30478036 · doi:10.1073/pnas.1810946115
What was done
High-depth whole mitochondrial DNA (mtDNA) sequencing was conducted on 17 individuals across three unrelated multigeneration families exhibiting high-level mtDNA heteroplasmy. Sequencing was independently performed and validated across three separate facilities: the authors' research laboratory and two CLIA/CAP-accredited diagnostic laboratories using multiple distinct analytical approaches to track mtDNA segregation patterns.
What was found
Three unrelated families comprising 17 individuals demonstrated mtDNA heteroplasmy levels ranging from 24% to 76%. Segregation analysis showed biparental mtDNA transmission behaving in an autosomal dominant-like pattern of inheritance.
Why it matters
This study provides molecular evidence that paternal mtDNA transmission can occur alongside maternal inheritance in exceptional human lineages, challenging the strict dogma that human mtDNA is exclusively maternal.
Limits
The study is limited to a small sample size (17 individuals in 3 families), preventing estimates of population prevalence. The specific nuclear or mitochondrial genetic mechanisms underlying this autosomal dominant-like paternal transmission were not identified in the abstract.
Cited by
- context Human mitochondrial DNA is 100% maternally inherited, and published claims of paternal mitochondrial inheritance were due to sequencing artifacts.