ArticleHuman genomics2010
Methylation-mediated deamination of 5-methylcytosine appears to give rise to mutations causing human inherited disease in CpNpG trinucleotides, as well as in CpG dinucleotides.
Article in Human genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 155 citations in OpenAlex.
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- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Methylation Dynamics inMicroorganisms · 2026Article
- Unsupervised Deep Representation Learning and Probabilistic Clustering for the Systems-Level Discovery of Germline Mutation Signatures in Pediatric Cancers.Biomedicines · 2026Article
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- Modulation of host gene expression by the zinc finger antiviral protein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic and Epigenetic Changes inLife (Basel, Switzerland) · 2025Article
- A Dirichlet-multinomial mixed model for determining differential abundance of mutational signatures.BMC bioinformatics · 2025Article
- Comparative transcriptomics and metabolomics provide insight into degeneration-related physiological mechanisms of Morchella importuna after long-term preservation.Microbial biotechnology · 2025Article
- Polymorphic pseudogenes in the human genome - a comprehensive assessment.Human genetics · 2024Article
- Benchmarking 13 tools for mutational signature attribution, including a new and improved algorithm.Briefings in bioinformatics · 2024Article
- Mutational signature analyses in multi-child families reveal sources of age-related increases in human germline mutations.Communications biology · 2024Article
- Human DNA polymerase ε is a source of C>T mutations at CpG dinucleotides.Nature genetics · 2024Article
- Prognostic Significance ofPhenomics (Cham, Switzerland) · 2024Article
- Evolutionary preservation of CpG dinucleotides in RAG1 may elucidate the relatively high rate of methylation-mediated mutagenesis of RAG1 transposase.Immunologic research · 2024Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytosine-guanine (CpG) dinucleotide has long been known to be a hotspot for pathological mutation in the human genome. This hypermutability is related to its role as the major site of cytosine methylation with the attendant risk of spontaneous deamination of 5-methylcytosine (5mC) to yield thymine. Cytosine methylation, however, also occurs in the context of CpNpG sites in the human genome, an unsurprising finding since the intrinsic symmetry of CpNpG renders it capable of supporting a semi-conservative model of replication of the methylation pattern. Recently, it has become clear that significant DNA methylation occurs in a CpHpG context (where H = A, C or T) in a variety of human somatic tissues. If we assume that CpHpG methylation also occurs in the germline, and that 5mC deamination can occur within a CpHpG context, then we might surmise that methylated CpHpG sites could also constitute mutation hotspots causing human genetic disease. To test this postulate, 54,625 missense and nonsense mutations from 2,113 genes causing inherited disease were retrieved from the Human Gene Mutation Database (http://www.hgmd.org). Some 18.2 per cent of these pathological lesions were found to be C → T and G → A transitions located in CpG dinucleotides (compatible with a model of methylation-mediated deamination of 5mC), an approximately ten-fold higher proportion than would have been expected by chance alone. The corresponding proportion for the CpHpG trinucleotide was 9.9 per cent, an approximately two-fold higher proportion than would have been expected by chance. We therefore estimate that ∼5 per cent of missense/nonsense mutations causing human inherited disease may be attributable to methylation-mediated deamination of 5mC within a CpHpG context.
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