ArticleProceedings of the National Academy of Sciences of the United States of America2019
Overlooked roles of DNA damage and maternal age in generating human germline mutations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 236 citations in OpenAlex.
- Dynamics of mutators of arbitrary dominance in humans.bioRxiv : the preprint server for biology · 2026Article
- Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.Archives of toxicology · 2026Review
- Spaceborne and spaceborn: Physiological aspects of pregnancy and birth during interplanetary flight.Experimental physiology · 2026Review
- Article
- Divergent Thermal Reaction Norms of the Spontaneous Mutation Rate Among Populations of Chironomus riparius.Molecular ecology · 2026Article
- Inferring the Relative Contributions of Evolutionary Processes Shaping X Chromosome Dynamics in the Common Marmoset (Callithrix jacchus) in the Presence of Twinning and Hematopoietic Chimerism.Genome biology and evolution · 2026Article
- AScience advances · 2026Article
- The Effect of Age and Sex on the Rate of Germline Mutations in Barn Owls.Genome biology and evolution · 2026Article
- Sperm DNA fragmentation: how to test, when to test, and what to do with abnormal results-a pragmatic mini-review for clinical practice.Human reproduction (Oxford, England) · 2026Review
- Evolution of the highest fidelity DNA replication systems.bioRxiv : the preprint server for biology · 2026Article
- What sets the mutation rate of a cell type in an animal species?PLoS biology · 2026Article
- Sequence context and methylation interact to shape germline mutation rate variation at CpG sites.PLoS genetics · 2026Article
- A sibling study of variation in parental mutation rates.bioRxiv : the preprint server for biology · 2026Article
- Sequence context and methylation interact to shape germline mutation rate variation at CpG sites.bioRxiv : the preprint server for biology · 2026Article
- Evolution of the rate, molecular spectrum, and fitness effects of mutation under minimal selection in Caenorhabditis elegans.Genetics · 2026Article
- Characterization of de novo germline mutations suggests a strong male mutation bias in coppery titi monkeys (Plecturocebus cupreus).Molecular biology and evolution · 2026Article
- Long-read sequencing of families reveals increased germline and postzygotic mutation rates in repetitive DNA.Nature communications · 2026Article
- Identification of de novo variants from parent-proband duos via long-read sequencing.American journal of human genetics · 2026Article
- Evolution of the rate, molecular spectrum, and fitness effects of mutation under minimal selection inbioRxiv : the preprint server for biology · 2026Article
- What sets the mutation rate of a cell type in an animal species?bioRxiv : the preprint server for biology · 2025Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The textbook view that most germline mutations in mammals arise from replication errors is indirectly supported by the fact that there are both more mutations and more cell divisions in the male than in the female germline. When analyzing large de novo mutation datasets in humans, we find multiple lines of evidence that call that view into question. Notably, despite the drastic increase in the ratio of male to female germ cell divisions after the onset of spermatogenesis, even young fathers contribute three times more mutations than young mothers, and this ratio barely increases with parental age. This surprising finding points to a substantial contribution of damage-induced mutations. Indeed, C-to-G transversions and CpG transitions, which together constitute over one-fourth of all base substitution mutations, show genomic distributions and sex-specific age dependencies indicative of double-strand break repair and methylation-associated damage, respectively. Moreover, we find evidence that maternal age at conception influences the mutation rate both because of the accumulation of damage in oocytes and potentially through an influence on the number of postzygotic mutations in the embryo. These findings reveal underappreciated roles of DNA damage and maternal age in the genesis of human germline mutations.
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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.