ArticleProceedings of the National Academy of Sciences of the United States of America2002
The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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.
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Who cites it
59 citing papers in PubMed, 165 citations in OpenAlex.
- Increased paternal age and the influence on burden of genomic copy number variation in the general population.Human genetics · 2013Trial
- Inference of elevated mutation rates and variant effects using 700k exomes.bioRxiv : the preprint server for biology · 2026Article
- Article
- Development of a Clinically Applicable High-Resolution Assay for Sperm Mosaicism.The Journal of molecular diagnostics : JMD · 2025Article
- Exploring FGFR3 Mutations in the Male Germline: Implications for Clonal Germline Expansions and Paternal Age-Related Dysplasias.Genome biology and evolution · 2024Article
- Exploring the Micro-Mosaic Landscape ofGenes · 2024Article
- Germline EGFR mutations in lung cancer (Review).Oncology letters · 2023Review
- The impact of paternal age on new mutations and disease in the next generation.Fertility and sterility · 2022Review
- Discovery of an unusually high number of de novo mutations in sperm of older men using duplex sequencing.Genome research · 2022Article
- An Update on Semen Physiology, Technologies, and Selection Techniques for the Advancement of In Vitro Equine Embryo Production: Section I.Animals : an open access journal from MDPI · 2021Review
- Prevention of guanylyl cyclase-B dephosphorylation rescues achondroplastic dwarfism.JCI insight · 2021Article
- Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells.The FEBS journal · 2021Review
- Article
- Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.Genome research · 2018Article
- Reproductive genetics and the aging male.Journal of assisted reproduction and genetics · 2018Review
- Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia.Scientific reports · 2017Article
- Artifactual mutations resulting from DNA lesions limit detection levels in ultrasensitive sequencing applications.DNA research : an international journal for rapid publication of reports on genes and genomes · 2016Article
- Male biological clock: a critical analysis of advanced paternal age.Fertility and sterility · 2015Review
- Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring.Reproductive biology and endocrinology : RB&E · 2015Review
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g., achondroplasia) increase in incidence with the age of the father is consistent with this idea. Although it is assumed that the paternal age effect is the result of an increasing frequency of mutant sperm as a man grows older, no direct molecular measurement of the germ-line mutation frequency has been made to confirm this hypothesis. Using sperm DNA from donors of different ages, we determined the frequency of the nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia. Surprisingly, the magnitude of the increase in mutation frequency with age appears insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives may explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and are inefficiently detected by the PCR assay.
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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.