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Epigenetics

Genetics shapes methylation and expression

Bell JT, Pai AA, Pickrell JK, et al. · Genome biology · 2011

Open access · cc by · source: Europe PMC

In HapMap LCLs, promoter methylation associates with genetic variants and transcript levels.

Study at a glance

Design
Cross-sectional — Illumina 27K promoter methylation in Yoruba HapMap LCLs linked to genotypes and RNA-seq
N
N=77 · 77 LCLs; RNA-seq available for 69
Population
HapMap Yoruba lymphoblastoid cell lines
Outcome
Genetic and expression correlates of inter-individual DNA methylation

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Inter-individual methylation variation tracks genetics and correlates with expression.

Methodology

Illumina 27K methylation in 77 Yoruba LCLs related to genotypes and RNA-seq.

Limitations

LCLs are transformed lines, so results may differ from primary tissues.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • SupportsEpigeneticsconcept

    Multiple empirical papers in this library examine epigenetics with mechanistic biological findings.

    Evidence for the claim as stated.

  • SupportsEpigeneticsconcept

    Inter-individual methylation variation tracks genetics and correlates with expression.

    Evidence for the claim as stated.

  • SupportsEpigeneticsconcept

    Systems and scales differ across epigenetics studies (species, tissues, methods), so mechanisms should not be over-generalised.

    Evidence for the claim as stated.

  • RNA-seq can be joined to genetics and to metabolites, still without proving causation. In 77 Yoruba LCLs, inter-individual methylation tracked genotypes and correlated with RNA-seq expression; in Panax ginseng, MEP-pathway expression patterns were taken to contribute to ginsenoside biosynthesis with IspD predicted as a key enzyme.

    Evidence for the claim as stated.

  • Reference-guided counting and de novo assembly are not interchangeable products. CircRNA detection needed non-poly(A) libraries and back-splice calling; Aloe and sea bass papers assemble transcripts because a complete reference is missing or incomplete; LCL and tomato papers quantify against known genes. Treating every RNA-seq paper as a gene-count table hides those design choices.

    Evidence for the claim as stated.

  • How far a transcriptome may be generalised is itself in dispute in these papers. Tomato red-light findings are not automatically all crops; mixed-yeast dilution rates are experimental; LCL methylation–expression links may not hold in primary tissues; coral DEGs do not settle field etiology.

    Evidence for the claim as stated.

  • Expression and methylation can be treated as GWAS-style traits (eQTLs, mQTLs). Liver expression–genotype maps linked common variants to metabolic pathways; in 77 Yoruba LCLs, methylation variation tracked genetics and RNA-seq expression. Those maps are still associations, not proof that each variant causes a disease endpoint.

    Evidence for the claim as stated.

  • SupportsBisulfite Sequencingmethod

    Illumina 27K methylation in 77 Yoruba lymphoblastoid cell lines tracked genotypes and correlated with RNA-seq expression. LCLs are transformed lines, so primary-tissue methylation may differ.

    Evidence for the claim as stated.

  • SupportsBisulfite Sequencingmethod

    Bisulfite designs here are not one map. VTRNA2-1 is a multi-tissue epiallele stable ≥10 years and sensitive to periconceptional season; the ageing paper compresses 102 AR-CpGs into a 3-site blood clock (MAD 3.34 years); Yoruba 27K arrays link methylation to genetics and expression in 77 LCLs. A clock CpG is not an environment-set metastable epiallele.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    Illumina 27K methylation in 77 Yoruba LCLs related to genotypes and RNA-seq: inter-individual methylation variation tracks genetics and correlates with expression. That is a methylation array plus RNA-seq, not ChIP-seq; LCLs may differ from primary tissues.

    Evidence for the claim as stated.

  • SupportsChIP-seqmethod

    Only the rice histone-acylation paper is clearly genome-wide ChIP-seq of chromatin marks (Kbu/Kcr versus H3K9ac under stress). Foxp3 work is candidate-locus ChIP; FECR1 is CasIP of promoter RNAs; Yoruba data are 27K methylation arrays. Treating them as one ChIP-seq method overstates shared technology.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

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