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<p>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 <i>cis</i>-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 <i>Capn11</i> and highly likely at <i>Vps37c</i>. 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.</p>

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Non-Mendelian inheritance of DNA methylation patterns in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

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  • Adam Davidovich,
  • Danila Cuomo,
  • Hang Su,
  • Sandeep Kambhampati,
  • Qingqing Gong,
  • Alexandra Naron,
  • Rakel Tryggvadottir,
  • Leonard McMillan,
  • Kasper D. Hansen,
  • David W. Threadgill,
  • Andrew P. Feinberg

摘要

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.