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Proc Natl Acad Sci U S A. 2018 Nov 26. pii: 201810946. doi: 10.1073/pnas.1810946115. [Epub ahead of print]

Biparental Inheritance of Mitochondrial DNA in Humans.

Author information

1
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
2
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003 Guangxi, China.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
4
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, 100 Taipei, Taiwan.
5
Department of Pediatrics, National Taiwan University Hospital, 100 Taipei, Taiwan.
6
Department of Clinical Genomics, Center for Individualized Medicine, Mayo Clinic Hospital, Jacksonville, FL 32224.
7
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; taosheng.huang@cchmc.org.

Abstract

Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.

KEYWORDS:

biparental inheritance; human genetics; mitochondria; mtDNA; paternal transmission

PMID:
30478036
DOI:
10.1073/pnas.1810946115

Conflict of interest statement

The authors declare no conflict of interest.

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