221: Allele-resolved nanopore tour of the human placental methylome

Kindlova M et al., Nat Commun - Using phased long-read nanopore and short-read sequencing across eight trios, the study maps allele-specific DNA methylation and transcription in female human placentas, identifies hundreds of DMRs and novel imprinted genes, and reports somatic placental variants. Key terms: placenta, nanopore sequencing, DNA methylation, imprinting, allele-specific expression. Study Highlights:The authors combined >20x Oxford Nanopore whole-genome sequencing with Illumina WGS and RNA-seq in eight mother–father–placenta trios to phase reads into maternal and paternal alleles. They catalogued 723 differentially methylated regions, finding a strong bias toward paternal demethylation concentrated in partially methylated domains. Allele-resolved expression analysis identified 74 imprinted genes and revealed previously unreported imprinted loci including paternally expressed ILDR2 and maternally expressed RASA1. The study also detected widespread somatic point mutations and a small number of placenta-specific structural variants, including a CNDP1–ZNF407 duplication associated with altered gene expression Conclusion:Phased nanopore sequencing provides a high-resolution, allele-specific map of the placental methylome and transcriptome, revealing novel imprinted genes and somatic variation with potential relevance to placental biology Music:Enjoy the music based on this article at the end of the episode. First author:Kindlova M Journal:Nat Commun DOI:10.1038/s41467-025-65337-3 Reference:Kindlova M, Byrne H, Kubler JM, Steane SE, Whyte JM, Borg D, Clifton VL & Ewing AD. An allele-resolved nanopore-guided tour of the human placental methylome. Nat Commun. 2025;16:10358. https://doi.org/10.1038/s41467-025-65337-3 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/allele-resolved-placental-methylome QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-07. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Substantively audited the transcript’s coverage of allele-resolved placental methylome mapping, DMRs, imprinting, specific imprinted genes ILDR2 and RASA1, the C19MC locus, SST1 repeats, somatic variation including CNDP1–ZNF407, and X-chromosome methylation, plus study limitations and conclusions.- transcript topics: Allele-resolved methylome mapping by nanopore sequencing; Trio-based phasing and parental allele assignment; Global methylation patterns and PMDs in placenta; Differentially methylated regions (DMRs) and paternal demethylation bias; Imprinted genes ILDR2 and RASA1; C19MC locus and SST1 macro-satellite region QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- Eight female placentas were sequenced in eight mother–father–placenta trios- Long-read nanopore sequencing with trio-based phasing enables allele-specific methylation and transcription mapping, with EM-seq validation showing high concordance (~94%)- Ident...