Biparental Inheritance of Mitochondrial DNA in Humans

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 multigen...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 115; no. 51; pp. 13039 - 13044
Main Authors Luo, Shiyu, Valencia, C. Alexander, Zhang, Jinglan, Lee, Ni-Chung, Slone, Jesse, Gui, Baoheng, Wang, Xinjian, Li, Zhuo, Dell, Sarah, Brown, Jenice, Chen, Stella Maris, Chien, Yin-Hsiu, Hwu, Wuh-Liang, Fan, Pi-Chuan, Wong, Lee-Jun, Atwal, Paldeep S., Huang, Taosheng
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 18.12.2018
Subjects
Adult
Biological Sciences
Child, Preschool
Databases, Genetic
Deoxyribonucleic acid
Disease transmission
DNA
DNA, Mitochondrial - genetics
Female
Genes, Mitochondrial
Genome, Mitochondrial
Heteroplasmy
Humans
Inheritance Patterns
Laboratories
Male
Maternal Inheritance
Middle Aged
Mitochondria
Mitochondria - genetics
Mitochondrial Diseases - genetics
Mitochondrial DNA
Molecules
Offspring
Paternal Inheritance
Pathology
Pedigree
biparental inheritance
human genetics
paternal transmission
mtDNA
mitochondria
Online AccessGet full text
ISSN0027-8424
1091-6490
1091-6490
DOI10.1073/pnas.1810946115

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Summary: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.
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2Present address: Center for Medical Genetics, School of Life Sciences, Central South University, 410008 Changsha, Hunan, China.
3P.S.A. and T.H. contributed equally to this work.
1Present address: Section of Molecular Genetics, PerkinElmer Genomics, Branford, CT 06405.
Author contributions: P.S.A. and T.H. designed research; S.L., J.Z., N.-C.L., J.S., B.G., Z.L., S.D., J.B., S.M.C., Y.-H.C., W.-L.H., and P.-C.F. performed research; S.L., C.A.V., J.Z., J.S., X.W., L.-J.W., and T.H. analyzed data; S.L., C.A.V., J.S., and T.H. wrote the paper; and N.-C.L., Y.-H.C., W.-L.H., P.-C.F., P.S.A., and T.H. evaluated patients and their families.
Edited by Douglas C. Wallace, Children’s Hospital of Philadelphia and University of Philadelphia, Philadelphia, PA, and approved October 29, 2018 (received for review June 26, 2018)
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1810946115