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DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines

ABSTRACT: We measured the methylation status at 27,578 CpG sites using the Human Methylation27 DNA array in 77 HapMap Yoruba lymphoblastoid cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26133 | GEO | 2011/01/05

SECONDARY ACCESSION(S): PRJNA135379

REPOSITORIES: GEO

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DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines

Project description:We measured the methylation status at 27,578 CpG sites using the Human Methylation27 DNA array in 77 HapMap Yoruba lymphoblastoid cell lines. Bisulphite converted DNA from 77 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip

2011-01-05 | E-GEOD-26133 | biostudies-arrayexpress

CTCF HAPMAP VARIATION

Project description:This study will look at variation in CTCF binding in humans as assayed by ChIP-seq on 60 HapMap lymphoblastoid cell lines.

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BLUEPRINT methylome of the HapMap cell line GM18507 (Coriell cell line NA18507)

Project description:Whole genome bisulfite sequencing (WGBS) of the NA18507 (Yoruba) lymphoblastoid cell line

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DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines.

Project description:DNA methylation is an essential epigenetic mechanism involved in gene regulation and disease, but little is known about the mechanisms underlying inter-individual variation in methylation profiles. Here we measured methylation levels at 22,290 CpG dinucleotides in lymphoblastoid cell lines from 77 HapMap Yoruba individuals, for which genome-wide gene expression and genotype data were also available.Association analyses of methylation levels with more than three million common single nucleotide polymorphisms (SNPs) identified 180 CpG-sites in 173 genes that were associated with nearby SNPs (putatively in cis, usually within 5 kb) at a false discovery rate of 10%. The most intriguing trans signal was obtained for SNP rs10876043 in the disco-interacting protein 2 homolog B gene (DIP2B, previously postulated to play a role in DNA methylation), that had a genome-wide significant association with the first principal component of patterns of methylation; however, we found only modest signal of trans-acting associations overall. As expected, we found significant negative correlations between promoter methylation and gene expression levels measured by RNA-sequencing across genes. Finally, there was a significant overlap of SNPs that were associated with both methylation and gene expression levels.Our results demonstrate a strong genetic component to inter-individual variation in DNA methylation profiles. Furthermore, there was an enrichment of SNPs that affect both methylation and gene expression, providing evidence for shared mechanisms in a fraction of genes.

| S-EPMC3091299 | biostudies-literature

Homo sapiens strain:(YRI) Yoruba HapMap population

Project description:CompleteGenomics sequencing of (YRI) Yoruba HapMap population

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BLUEPRINT methylome of the HapMap cell line GM18507 (Coriell cell line NA18507)

Project description:Whole genome bisulfite sequencing (WGBS) of the NA18507 (Yoruba) lymphoblastoid cell line high resolution methylome of one cell type

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Homo sapiens strain:(YRI) Yoruba HapMap population

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Genome-wide baseline microRNA expression quantification in HapMap phase I CEU and YRI samples

Project description:Baseline microRNA (miRNA) expression was evaluated in 107 HapMap lymphoblastoid cell lines (LCLs; 53 CEU and 54 YRI) using Exiqon miRCURY LNA arrays v10.0 (Exiqon array).

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Identification of genetic variants that affect histone modifications in human cells

Project description:Histone modifications are important markers of function and chromatin state, yet the DNA elements that direct them to specific locations in the genome are poorly understood. Here we use the genetic variation in Yoruba lymphoblastoid cell lines as a natural experiment to identify genetic differences that affect histone marks and to better understand their relationship with transcriptional regulation. Across the genome, we identified hundreds of quantitative trait loci that impact histone modification or RNA polymerase (PolII) occupancy. In many cases the same variant is associated with quantitative changes in multiple histone marks and PolII, as well as in DNaseI sensitivity and nucleosome positioning, indicating that these molecular phenotypes often share a single underlying genetic cause. Variants that impact chromatin at distal regulatory sites frequently also direct changes in chromatin and gene expression at associated promoters; while most of these distal regulators enhance promoter activity, some act as distal chromatin silencers. Finally, we find that polymorphisms in transcription factor binding sites are often causally responsible for variation in local histone modification. In summary, the class of variants identified here generate coordinated changes in chromatin both locally and sometimes at distant locations, frequently drive changes in gene expression, and likely play an important role in the genetics of complex traits. ChIP-seq of RNA Polymerase II and 4 histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3) in 10 unrelated Yoruba HapMap lymphoblastoid cell lines

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