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Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.

Publication ,  Journal Article
Bai, R; Cui, H; Devaney, JM; Allis, KM; Balog, AM; Liu, X; Schnur, RE; Shapiro, FL; Brautbar, A; Estrada-Veras, JI; Hochstetler, L; Hofherr, S ...
Published in: Genet Med
August 2021

PURPOSE: Reports have questioned the dogma of exclusive maternal transmission of human mitochondrial DNA (mtDNA), including the recent report of an admixture of two mtDNA haplogroups in individuals from three multigeneration families. This was interpreted as being consistent with biparental transmission of mtDNA in an autosomal dominant-like mode. The authenticity and frequency of these findings are debated. METHODS: We retrospectively analyzed individuals with two mtDNA haplogroups from 2017 to 2019 and selected four families for further study. RESULTS: We identified this phenomenon in 104/27,388 (approximately 1/263) unrelated individuals. Further study revealed (1) a male with two mitochondrial haplogroups transmits only one haplogroup to some of his offspring, consistent with nuclear transmission; (2) the heteroplasmy level of paternally transmitted variants is highest in blood, lower in buccal, and absent in muscle or urine of the same individual, indicating it is inversely correlated with mtDNA content; and (3) paternally transmitted apparent large-scale mtDNA deletions/duplications are not associated with a disease phenotype. CONCLUSION: These findings strongly suggest that the observed mitochondrial haplogroup of paternal origin resulted from coamplification of rare, concatenated nuclear mtDNA segments with genuine mtDNA during testing. Evaluation of additional specimen types can help clarify the clinical significance of the observed results.

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Published In

Genet Med

DOI

EISSN

1530-0366

Publication Date

August 2021

Volume

23

Issue

8

Start / End Page

1514 / 1521

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Phenotype
  • Mitochondria
  • Male
  • Humans
  • Haplotypes
  • Genetics & Heredity
  • DNA, Mitochondrial
  • 3105 Genetics
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Bai, R., Cui, H., Devaney, J. M., Allis, K. M., Balog, A. M., Liu, X., … Suchy, S. F. (2021). Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans. Genet Med, 23(8), 1514–1521. https://doi.org/10.1038/s41436-021-01166-1
Bai, Renkui, Hong Cui, Joseph M. Devaney, Katrina M. Allis, Amanda M. Balog, Xinyue Liu, Rhonda E. Schnur, et al. “Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.Genet Med 23, no. 8 (August 2021): 1514–21. https://doi.org/10.1038/s41436-021-01166-1.
Bai R, Cui H, Devaney JM, Allis KM, Balog AM, Liu X, et al. Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans. Genet Med. 2021 Aug;23(8):1514–21.
Bai, Renkui, et al. “Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans.Genet Med, vol. 23, no. 8, Aug. 2021, pp. 1514–21. Pubmed, doi:10.1038/s41436-021-01166-1.
Bai R, Cui H, Devaney JM, Allis KM, Balog AM, Liu X, Schnur RE, Shapiro FL, Brautbar A, Estrada-Veras JI, Hochstetler L, McConkie-Rosell A, McDonald MT, Solomon BD, Hofherr S, Richard G, Suchy SF. Interference of nuclear mitochondrial DNA segments in mitochondrial DNA testing resembles biparental transmission of mitochondrial DNA in humans. Genet Med. 2021 Aug;23(8):1514–1521.

Published In

Genet Med

DOI

EISSN

1530-0366

Publication Date

August 2021

Volume

23

Issue

8

Start / End Page

1514 / 1521

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Phenotype
  • Mitochondria
  • Male
  • Humans
  • Haplotypes
  • Genetics & Heredity
  • DNA, Mitochondrial
  • 3105 Genetics
  • 1103 Clinical Sciences