ReviewAmerican journal of human genetics2012
Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease.
Review in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 4 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
174 citing papers in PubMed, 4 syntheses or guidelines pooled it, 356 citations in OpenAlex.
- A systematic review on the role of paternal factors in human placental development, function, and pregnancy-related disorders.Journal of assisted reproduction and genetics · 2025Pooled it
- Fertility in the aging male: a systematic review.Fertility and sterility · 2022Pooled it
- CTBP1 and CTBP2 mutations underpinning neurological disorders: a systematic review.Neurogenetics · 2022Pooled it
- Effects of aging on the male reproductive system.Journal of assisted reproduction and genetics · 2016Pooled it
- Effect of parental age on treatment response in adolescents with schizophrenia.Schizophrenia research · 2013Trial
- Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.Nature medicine · 2026Article
- Age-related decline in niche self-renewal factors drives testis aging via Hairless, Imp, and Chinmo.Science advances · 2026Article
- Clonal dynamics deviate from neutral drift in zebrafish spermatogenesis.bioRxiv : the preprint server for biology · 2026Article
- Long-term survival without high cancer risk in a cohort of 24 patients with Apert syndrome.European journal of human genetics : EJHG · 2026Article
- How somatic evolution affects health.Nature ecology & evolution · 2026Article
- A distributive germline restricts the spread of new mutations.bioRxiv : the preprint server for biology · 2026Article
- Scalable and comprehensive mosaic variant calling using DRAGEN.medRxiv : the preprint server for health sciences · 2026Article
- Recent Progress in Characterizing Germline Mutations and Their Transmission Across Generations.Advances in experimental medicine and biology · 2026Review
- The Risk of Transmission of Genetic Prion Diseases is Greater Than 50.European journal of neurology · 2025Article
- Differential expression of reproduction and sex-determining genes in the gonads of genotypic and temperature-induced males of gibel carp (Carassius gibelio).Scientific reports · 2025Article
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- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- Houge-Janssens syndrome.European journal of human genetics : EJHG · 2025Review
114 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
2 authors at 1 institution in 1 country.
Funding
Abstract
Advanced paternal age has been associated with an increased risk for spontaneous congenital disorders and common complex diseases (such as some cancers, schizophrenia, and autism), but the mechanisms that mediate this effect have been poorly understood. A small group of disorders, including Apert syndrome (caused by FGFR2 mutations), achondroplasia, and thanatophoric dysplasia (FGFR3), and Costello syndrome (HRAS), which we collectively term "paternal age effect" (PAE) disorders, provides a good model to study the biological and molecular basis of this phenomenon. Recent evidence from direct quantification of PAE mutations in sperm and testes suggests that the common factor in the paternal age effect lies in the dysregulation of spermatogonial cell behavior, an effect mediated molecularly through the growth factor receptor-RAS signal transduction pathway. The data show that PAE mutations, although arising rarely, are positively selected and expand clonally in normal testes through a process akin to oncogenesis. This clonal expansion, which is likely to take place in the testes of all men, leads to the relative enrichment of mutant sperm over time-explaining the observed paternal age effect associated with these disorders-and in rare cases to the formation of testicular tumors. As regulation of RAS and other mediators of cellular proliferation and survival is important in many different biological contexts, for example during tumorigenesis, organ homeostasis and neurogenesis, the consequences of selfish mutations that hijack this process within the testis are likely to extend far beyond congenital skeletal disorders to include complex diseases, such as neurocognitive disorders and cancer predisposition.
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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.