Evidence map›Paper›PMID 27770035›Full record

ArticleGenetics2016

Replication Errors Made During Oogenesis Lead to Detectable De Novo mtDNA Mutations in Zebrafish Oocytes with a Low mtDNA Copy Number.

Auke B C Otten, Alphons P M Stassen, Michiel Adriaens, Mike Gerards, Richard G J Dohmen, Adriana J Timmer, Sabina J V Vanherle, Rick Kamps, Iris B W Boesten, Jo M Vanoevelen and 2 more

Abstract read
In one paragraph

Article in Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Mutations of mitochondrial DNA are not major contributors to aging of fruit flies.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  9. Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Auke B C OttenDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.ORCID http://orcid.org/0000-0001-5034-9743
Alphons P M StassenDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Michiel AdriaensMaastricht Centre for Systems Biology, Maastricht University, 6200 MD, The Netherlands.ORCID http://orcid.org/0000-0002-4472-7119
Mike GerardsMaastricht Centre for Systems Biology, Maastricht University, 6200 MD, The Netherlands.
Richard G J DohmenDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Adriana J TimmerDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Sabina J V VanherleDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Rick KampsDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Iris B W BoestenDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Jo M VanoevelenDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands.
Marc MullerLaboratory of Organogenesis and Regeneration, Interdisciplinary Cluster for Applied Genoproteomics Research, Univérsité de Liège, 4000, Belgium.
Hubert J M SmeetsDepartment of Genetics and Cell Biology, Clinical Genomics Unit, School for Oncology and Developmental Biology, Maastricht University, 6200 MD, The Netherlands bert.smeets@maastrichtuniversity.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Of all pathogenic mitochondrial DNA (mtDNA) mutations in humans, ∼25% is de novo, although the occurrence in oocytes has never been directly assessed. We used next-generation sequencing to detect point mutations directly in the mtDNA of 3-15 individual mature oocytes and three somatic tissues from eight zebrafish females. Various statistical and biological filters allowed reliable detection of de novo variants with heteroplasmy ≥1.5%. In total, we detected 38 de novo base substitutions, but no insertions or deletions. These 38 de novo mutations were present in 19 of 103 mature oocytes, indicating that ∼20% of the mature oocytes carry at least one de novo mutation with heteroplasmy ≥1.5%. This frequency of de novo mutations is close to that deducted from the reported error rate of polymerase gamma, the mitochondrial replication enzyme, implying that mtDNA replication errors made during oogenesis are a likely explanation. Substantial variation in the mutation prevalence among mature oocytes can be explained by the highly variable mtDNA copy number, since we previously reported that ∼20% of the primordial germ cells have a mtDNA copy number of ≤73 and would lead to detectable mutation loads. In conclusion, replication errors made during oogenesis are an important source of de novo mtDNA base substitutions and their location and heteroplasmy level determine their significance.

Indexed as

DNA ReplicationGene DosageMutationOogenesisAnimalsDNA, MitochondrialFemaleMutation RateOocytesZebrafishDNA, Mitochondrialde novo mutationsmitochondrial DNAnext-generation sequencingoogenesiszebrafish

Identifiers

PMID27770035
PMCPMC5161276

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.