ArticleProceedings of the National Academy of Sciences of the United States of America2015
The genetics of human infertility by functional interrogation of SNPs in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 70 citations in OpenAlex.
- Wee Kinases, Big Impact: Wee and Myt Kinases as Critical Regulators of Meiotic Progression.Journal of developmental biology · 2026Review
- Genetic and epigenetic landscape of male infertility.Trends in genetics : TIG · 2025Review
- Disruption ineLife · 2024Article
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- Identification of a missense variant of MND1 in meiotic arrest and non-obstructive azoospermia.Journal of human genetics · 2023Article
- In vivo versus in silico assessment of potentially pathogenic missense variants in human reproductive genes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Reproductive genomics of the mouse: implications for human fertility and infertility.Development (Cambridge, England) · 2023Article
- Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.Reproductive biology and endocrinology : RB&E · 2022Article
- Computationally predicted pathogenicZoological research · 2022Article
- Pathogenic variations in Germ Cell Nuclear Acidic Peptidase (GCNA) are associated with human male infertility.European journal of human genetics : EJHG · 2021Article
- Cyclin E in normal physiology and disease states.Trends in cell biology · 2021Review
- Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.Nature communications · 2021Article
- Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure.Human genetics · 2021Article
- Strategies to Identify Genetic Variants Causing Infertility.Trends in molecular medicine · 2021Review
- Mini-Review Regarding the Applicability of Genome Editing Techniques Developed for Studying Infertility.Diagnostics (Basel, Switzerland) · 2021Review
- Article
- A framework for high-resolution phenotyping of candidate male infertility mutants: from human to mouse.Human genetics · 2021Review
- Genes Regulating Spermatogenesis and Sperm Function Associated With Rare Disorders.Frontiers in cell and developmental biology · 2021Review
- Variants in RABL2A causing male infertility and ciliopathy.Human molecular genetics · 2020Article
- A novel function for CDK2 activity at meiotic crossover sites.PLoS biology · 2020Article
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
Infertility is a prevalent health issue, affecting ∼15% of couples of childbearing age. Nearly one-half of idiopathic infertility cases are thought to have a genetic basis, but the underlying causes are largely unknown. Traditional methods for studying inheritance, such as genome-wide association studies and linkage analyses, have been confounded by the genetic and phenotypic complexity of reproductive processes. Here we describe an association- and linkage-free approach to identify segregating infertility alleles, in which CRISPR/Cas9 genome editing is used to model putatively deleterious nonsynonymous SNPs (nsSNPs) in the mouse orthologs of fertility genes. Mice bearing "humanized" alleles of four essential meiosis genes, each predicted to be deleterious by most of the commonly used algorithms for analyzing functional SNP consequences, were examined for fertility and reproductive defects. Only a Cdk2 allele mimicking SNP rs3087335, which alters an inhibitory WEE1 protein kinase phosphorylation site, caused infertility and revealed a novel function in regulating spermatogonial stem cell maintenance. Our data indicate that segregating infertility alleles exist in human populations. Furthermore, whereas computational prediction of SNP effects is useful for identifying candidate causal mutations for diverse diseases, this study underscores the need for in vivo functional evaluation of physiological consequences. This approach can revolutionize personalized reproductive genetics by establishing a permanent reference of benign vs. infertile alleles.
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.