Mental Health RAISR4D

Non-Mendelian inheritance of DNA methylation patterns in mice

21/05/2026

AI Summary

Genome-wide long-read nanopore sequencing enables allele-resolved analysis of DNA methylation inheritance in mouse liver and muscle.
Approximately 93% of autosomal methylation patterns obey Mendelian inheritance, predominantly driven by cis-acting methylation quantitative trait loci.
About 7% of autosomal patterns are non-Mendelian: emergent inheritance, liver sex-specific methylation, five novel imprinted genes, and paramutation at Capn11 and likely Vps37c.

Nat Genet. 2026 May 20. doi: 10.1038/s41588-026-02604-z. Online ahead of print.

ABSTRACT

Epigenetic mechanisms such as genomic imprinting demonstrate that molecular inheritance can deviate from typical Mendelian patterns. Despite this, the intergenerational inheritance of DNA methylation remains poorly understood. Here we developed a genome-wide approach to study epigenetic inheritance in mice using long-read nanopore sequencing. Using this approach in both liver and muscle, we found that ~93% of autosomal epigenetic inheritance patterns followed Mendel’s laws, primarily driven by cis-acting methylation quantitative trait loci. However, we also identified extensive non-Mendelian inheritance, including emergent epigenetic inheritance patterns, widespread sex-specific DNA methylation patterns localized to the liver, and five seemingly new autosomal and X-linked imprinted genes. Notably, we also report an example of naturally occurring intergenerational paramutation, confirmed over strain-specific transposable elements within Capn11 and highly likely at Vps37c. Overall, an unexpectedly high ~7% of autosomal epigenetic inheritance patterns identified were non-Mendelian, highlighting the importance of epigenetic information in the analysis of inherited traits and disorders.

PMID:42162411 | DOI:10.1038/s41588-026-02604-z

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