Quasi-Mendelian paternal inheritance of mitochondrial DNA: A notorious artifact, or anticipated behavior?

Annis, Sofia; Fleischmann, Zoë; Khrapko, Mark; Franco, Melissa; Wasko, Kevin; Woods, Dori C.; Kunz, Wolfram S.; Ellis, Peter J. I.; Khrapko, Konstantin

doi:10.1073/pnas.1821436116

Cited by 17 publications

(11 citation statements)

References 8 publications

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“…These results were explained with biparental inheritance of mtDNA. However, these conclusions were challenged ( 58 , 59 , 64 , 65 ) because the authors failed to exclude a significant NUMT contribution to the observed mixture by experimental work such as described herein. There are striking similarities between the study of Luo et al.…”

Section: Discussionmentioning

confidence: 88%

“…The following considerations suggest the presence of a full mitogenome NUMT as opposed to partial mitogenome sequences. The PCR amplification of the entire human mitogenome by generating two ∼8.5 kb fragments overlapping at both ends is straightforward when starting from a circular template (see Supplementary Figure S1 in ( 59 )). However, with a linear target such as a NUMT sequence, the situation is more complicated.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for multi-copy Mega-NUMTsin the human genome

Lutz-Bonengel

Niederstätter

Naue

et al. 2021

Nucleic Acids Research

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The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Evidence for multi-copy Mega-NUMTsin the human genome

Lutz-Bonengel

Niederstätter

Naue

et al. 2021

Nucleic Acids Research

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“…As we outline in this review, paternal contribution to mtDNA inheritance has also been suggested recently using MPS based techniques [14]. The conclusions in Luo et al2018 were challenged [15][16][17], and an alternative explanation for the observations was offered [16] that is the focus of this review -NUMTsnuclear elements of mtDNA.…”

Section: Introductionmentioning

confidence: 84%

Interpreting NUMTs in forensic genetics: Seeing the forest for the trees

Marshall

Parson

2021

Forensic Science International: Genetics

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Nuclear mitochondrial DNA (mtDNA) segments (NUMTs) were discovered shortly after sequencing the first human mitochondrial genome. They have earlier been considered to represent archaic elements of ancient insertion events, but modern sequencing technologies and growing databases of mtDNA and NUMT sequences confirm that they are abundant and some of them phylogenetically young. Here, we build upon mtDNA/NUMT review articles published in the mid 2010 s and focus on the distinction of NUMTs and other artefacts that can be observed in aligned sequence reads, such as mixtures (contamination), point heteroplasmy, sequencing error and cytosine deamination. We show practical examples of the effect of the mtDNA enrichment method on the representation of NUMTs in the mapped sequence data and discuss methods to bioinformatically filter NUMTs from mtDNA reads.

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“…It is of common knowledge that mtDNA is maternally inherited. In fact, despite some evidence of a biparental inheritance of mtDNA having been proposed [15], this hypothesis lacks definite confirmation [16][17][18][19].…”

Section: Mitochondrial Dna: From Genetics To Epigeneticsmentioning

confidence: 96%

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

Bordoni

Gabbianelli

2020

Antioxidants

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The maintenance of the mitochondrial function is essential in preventing and counteracting neurodegeneration. In particular, mitochondria of neuronal cells play a pivotal role in sustaining the high energetic metabolism of these cells and are especially prone to oxidative damage. Since overproduction of reactive oxygen species (ROS) is involved in the pathogenesis of neurodegeneration, dietary antioxidants have been suggested to counteract the detrimental effects of ROS and to preserve the mitochondrial function, thus slowing the progression and limiting the extent of neuronal cell loss in neurodegenerative disorders. In addition to their role in the redox-system homeostasis, mitochondria are unique organelles in that they contain their own genome (mtDNA), which acts at the interface between environmental exposures and the molecular triggers of neurodegeneration. Indeed, it has been demonstrated that mtDNA (including both genetics and, from recent evidence, epigenetics) might play relevant roles in modulating the risk for neurodegenerative disorders. This mini-review describes the link between the mitochondrial genome and cellular oxidative status, with a particular focus on neurodegeneration; moreover, it provides an overview on potential beneficial effects of antioxidants in preserving mitochondrial functions through the protection of mtDNA.

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Quasi-Mendelian paternal inheritance of mitochondrial DNA: A notorious artifact, or anticipated behavior?

Cited by 17 publications

References 8 publications

Evidence for multi-copy Mega-NUMTsin the human genome

Evidence for multi-copy Mega-NUMTsin the human genome

Interpreting NUMTs in forensic genetics: Seeing the forest for the trees

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

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