ArticleeLife2019
Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
138 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Meta-analysis of 46,000 germline de novo mutations linked to human inherited disease.Human genomics · 2024Pooled it
- Fertility in the aging male: a systematic review.Fertility and sterility · 2022Pooled it
- Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.Nature medicine · 2026Article
- Dynamics of mutators of arbitrary dominance in humans.bioRxiv : the preprint server for biology · 2026Article
- EstimatingbioRxiv : the preprint server for biology · 2026Article
- Landscape of parental postzygotic mutations across >11,000 rare disease trios.American journal of human genetics · 2026Article
- Population-scale Y chromosome assemblies reveal recurrent remodeling within constrained architectures.bioRxiv : the preprint server for biology · 2026Article
- 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
- A sibling study of variation in parental mutation rates.bioRxiv : the preprint server for biology · 2026Article
- Diverse mediators of cancer predisposition uncovered by germline whole genome sequencing of unexplained familial cancers.medRxiv : the preprint server for health sciences · 2026Article
- A family portrait of the genomic factors shaping tandem repeat mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- AVITI sequencing of a four-generation CEPH/Utah pedigree confirms low mutation rates at homopolymer loci despite their low sequence complexity.Genome biology · 2026Article
- Colibactin-associated mutations in the human colon appear to reflect anatomy and early exposure, not oncogenesis.medRxiv : the preprint server for health sciences · 2026Article
- A phylogenetic estimate of canine retrotransposition rates based on genome assembly comparisons.Mobile DNA · 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
- The mutation landscape of Daphnia obtusa reveals evolutionary forces shaping genome stability.Molecular biology and evolution · 2026Article
- What sets the mutation rate of a cell type in an animal species?bioRxiv : the preprint server for biology · 2025Article
- Inherent instability of simple DNA repeats shapes an evolutionarily stable distribution of repeat lengths.Nature communications · 2025Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
The number of de novo mutations (DNMs) found in an offspring's genome increases with both paternal and maternal age. But does the rate of mutation accumulation in human gametes differ across families? Using sequencing data from 33 large, three-generation CEPH families, we observed significant variability in parental age effects on DNM counts across families, ranging from 0.19 to 3.24 DNMs per year. Additionally, we found that ~3% of DNMs originated following primordial germ cell specification in a parent, and differed from non-mosaic germline DNMs in their mutational spectra. We also discovered that nearly 10% of candidate DNMs in the second generation were post-zygotic, and present in both somatic and germ cells; these gonosomal mutations occurred at equivalent frequencies on both parental haplotypes. Our results demonstrate that rates of germline mutation accumulation vary among families with similar ancestry, and confirm that post-zygotic mosaicism is a substantial source of human DNM.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.