ArticleHuman molecular genetics2013
New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed, 62 citations in OpenAlex.
- Stem cell competition.Current topics in developmental biology · 2026Review
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.American journal of human genetics · 2024Article
- 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
- Expression profiles of circular RNAs in spermatozoa from aging men.Molecular biology reports · 2023Article
- Achondroplasia: Clinical, Radiological and Molecular Profile from Rare Disease Centre, India.Journal of pediatric genetics · 2023Article
- The impact of paternal age on new mutations and disease in the next generation.Fertility and sterility · 2022Review
- Article
- Discovery of an unusually high number of de novo mutations in sperm of older men using duplex sequencing.Genome research · 2022Article
- Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia.BMC medical genomics · 2021Article
- The Mare: A Pertinent Model for Human Assisted Reproductive Technologies?Animals : an open access journal from MDPI · 2021Review
- Meiosis and beyond - understanding the mechanistic and evolutionary processes shaping the germline genome.Biological reviews of the Cambridge Philosophical Society · 2021Review
- Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells.The FEBS journal · 2021Review
- New developments in the management of achondroplasia.Wiener medizinische Wochenschrift (1946) · 2020Review
- Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations.Orphanet journal of rare diseases · 2019Article
- Functional robustness of adult spermatogonial stem cells after induction of hyperactive Hras.PLoS genetics · 2019Article
- Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes.Genome research · 2018Article
- Current Care and Investigational Therapies in Achondroplasia.Current osteoporosis reports · 2017Review
- Achondroplasia: Development, pathogenesis, and therapy.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10(-6). We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism.
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.