ArticleNature communications2021
Human MLH1/3 variants causing aneuploidy, pregnancy loss, and premature reproductive aging.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- A human CEP120 gene variant impairs meiotic spindle building causing aneuploidy†.Biology of reproduction · 2026Article
- Maternal MLH3 dysfunction drives unexplained recurrent pregnancy loss via impaired oocyte maturation and defective decidualization.Cellular and molecular life sciences : CMLS · 2026Article
- The DNA mismatch repair protein Msh4 is essential for meiosis of male but not for female in zebrafish.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2026Article
- Double jeopardy: howFrontiers in cell and developmental biology · 2026Review
- Disentangling the mutational effects on protein stability and interaction of human MLH1.PLoS genetics · 2025Article
- ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure.Cell death and differentiation · 2025Article
- Article
- The clinical application and challenges of preimplantation genetic testing.Frontiers in genetics · 2025Review
- Whole-exome sequencing and Drosophila modelling reveal mutated genes and pathways contributing to human ovarian failure.Reproductive biology and endocrinology : RB&E · 2024Article
- A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background.Journal of ovarian research · 2024Article
- Maternal genetic variants in kinesin motor domains prematurely increase egg aneuploidy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reproductive genetics and health.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2024Article
- Review
- Single-Cell Transcriptome Analysis Reveals Development-Specific Networks at Distinct Synchronized Antral Follicle Sizes in Sheep Oocytes.International journal of molecular sciences · 2024Article
- A novel recombination protein C12ORF40/REDIC1 is required for meiotic crossover formation.Cell discovery · 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
- Review
- SPIDR is required for homologous recombination during mammalian meiosis.Nucleic acids research · 2023Article
- Ste20-like kinase activity promotes meiotic resumption and spindle microtubule stability in mouse oocytes.Cell proliferation · 2023Article
- Construction of a DDR-related signature for predicting of prognosis in metastatic colorectal carcinoma.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Embryonic aneuploidy from mis-segregation of chromosomes during meiosis causes pregnancy loss. Proper disjunction of homologous chromosomes requires the mismatch repair (MMR) genes MLH1 and MLH3, essential in mice for fertility. Variants in these genes can increase colorectal cancer risk, yet the reproductive impacts are unclear. To determine if MLH1/3 single nucleotide polymorphisms (SNPs) in human populations could cause reproductive abnormalities, we use computational predictions, yeast two-hybrid assays, and MMR and recombination assays in yeast, selecting nine MLH1 and MLH3 variants to model in mice via genome editing. We identify seven alleles causing reproductive defects in mice including female subfertility and male infertility. Remarkably, in females these alleles cause age-dependent decreases in litter size and increased embryo resorption, likely a consequence of fewer chiasmata that increase univalents at meiotic metaphase I. Our data suggest that hypomorphic alleles of meiotic recombination genes can predispose females to increased incidence of pregnancy loss from gamete aneuploidy.
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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.