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Haplotype-resolved methylation profiling across three generations reveals principles of human epigenetic inheritance - PubMed

7 hours ago
  • #Haplotype-resolved profiling
  • #Epigenetic inheritance
  • #DNA methylation
  • Performed haplotype-resolved, whole-genome DNA methylation profiling in a three-generation Chinese family using long-read sequencing (ONT and PacBio HiFi) anchored to a T2T genome assembly.
  • Found globally conserved bimodal methylation landscapes, with distinct hypomethylation in centromeres and hypermethylation in retrotransposons/repetitive elements.
  • Identified domain-specific methylation patterns in rDNA arrays, showing hypomethylation in the transcriptional core and hypermethylation in the intergenic spacer, with age-associated epigenetic drift.
  • Mapped 23 high-confidence imprinting control regions (ICRs) with parent-of-origin-specific methylation, overlapping known imprinted genes and enriched for regulatory elements.
  • Uncovered sex- and allele-specific methylation patterns on the X chromosome linked to X inactivation dynamics, delineating principles of intergenerational epigenetic inheritance.