DNA methylation landscape of ocular tissue relative to matched peripheral blood
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Alex Hewitt
PROVIDER: E-MTAB-5535 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We report that the DNA methylation profile of a child’s neonatal whole blood can be significantly influenced by his or her mother’s neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children’s neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren’s neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren. For the study, we selected 35 dried blood spots (DBS) collected from mother-infant pairs from Health Fairs ran in three Detroit communities, because they have a high prevalence (8-11%) of high BLL in children. The sample set consisted of 25 male children and 18 female children. We also collected the neonatal DBS and mother neonatal DBS for these mother-infant pairs from the Michigan Neonatal Biobank. Then we measured a blood lead levels in dried blood spots using using atomic absorbtion spectrophotometry. Finally we measured the DNA methylation levels using human methylation 450K array from Illumina. Then we normalized the data for technical biases and tried to infer the the locus specific DNA methylation changes due to Pb exposure which was carried over from the grandmothers to the grandchildren by the Pb –exposed fetal germ cells of the mother using statistical model proposed by Sofer et al, 2012.
2015-04-01 | E-GEOD-67444 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of DNA extracted from dried blood spots from preterm and term subjects using longitudinal samples collected at birth and 18 years of age. Infinium HM450 arrays were used to measure methylation at 347,789 autosomal CpGs. DNA was analysed from individuals at birth and 18-years and included 12 preterm and 12 term controls. Bisulphite converted DNA from the 48 samples were hybridised to the Illumina Infinium 450K Human Methylation Beadchip
2013-10-20 | E-GEOD-51180 | biostudies-arrayexpress
Project description:Regulatory T cells (Treg) prevent the emergence of autoimmune disease. Prototypic natural Treg (nTreg) are programmed by Forkhead-box P3 (FOXP3) and can be reliably identified by demethylation at the FOXP3 locus. To explore the nTreg methylation landscape we performed genome-wide methylation studies on human naïve resting nTreg (rTreg) and conventional naïve CD4+ T cells (Naïve). We detected 2,315 differentially methylated CpGs between these two cell types, many of which clustered into 127 regions of differential methylation (RDMs). T cell activation induced changes in 466 individual CpGs and 18 RDMs in naïve CD4+ T cells, but did not alter DNA methylation in rTreg. Expression of mRNA for TIGIT, an immune suppressive receptor demethylated in rTreg, was upregulated in nTreg and reduced in peripheral blood mononuclear cells of individuals at risk for autoimmune (type 1) diabetes. Gene-set testing of the 127 RDMs revealed enrichment of common Treg signature genes, FOXP3 bound genes and genes directly upregulated by FOXP3, which was primarily driven by the subset of demethylated RDMs. A putative Forkhead-binding motif overrepresented in promoter-associated RDMs suggests methylation regulates gene expression by influencing FOXP3 binding. Our findings provide new insights into epigenetic regulation of human nTreg and the potential to exploit differential methylation as an immune biomarker in human diseases. Naïve and rTreg cells were sorted from buffy coats of 3 healthy male donors (M28, 29, 30) and then activated for 6 days with anti-CD3 and anti-CD28 antibodies, supplemented with IL-2 at day 4. DNA was harvested and bisulfite converted for methylation analysis on illumina HM450 array from 2-3 biological replicates of each cell type: rTreg (M28, M30), naïve (M28, M29, M30), Act-naïve (M28, M29, M30) and Act-rTreg (M29, M30).
2013-09-09 | E-GEOD-49667 | biostudies-arrayexpress
Project description:DNA methylation profiling of whole blood using Illumina's Infinium HumanMethylation27 Beadchip array. The dataset encompasses profiles of 12 non-diabetic control blood donors and 12 type-2 diabetic (T2D) individuals. Bisulfite converted DNA from 24 blood samples were hybridised to the Illumina Infinium HumanMethylation27 Beadchip
2012-04-22 | E-GEOD-34008 | biostudies-arrayexpress
Project description:Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (M-NM-^TYOM-bM-^@M-^I>M-bM-^@M-^I5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression. Peripheral blood mononuclear cells were isolated from 10 volunteers (5 young 5 old), treated with the synthetic PPARalpha agonists WY14,643 or control for 13 hrs, and subjected to genome-wide DNA methylation and gene expression analysis. This entry contains the DNA methylation data.
2014-05-09 | E-GEOD-49064 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling in infant's blood from a mother/child cohort in The Gambia. The main variables of the analyses were the intra-uterine exposure to aflatoxin B1 (AFB1) and the season of conception. The Illumina Infinium HumanMethylation 450k Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in whole peripheral blood obtained at 3-6 months of age. A total of 124 samples were analysed, including 3 technical replicates. Bisulphite converted DNA from the 124 samples were hybridised to the Illumina Infinium HumanMethylation 450k Beadchip
2015-04-18 | E-GEOD-59592 | biostudies-arrayexpress
Project description:Background: The mechanisms of how genetic variants (SNPs) identified in genome-wide association studies act to influence body mass remain unknown for most of these SNPs, which continue to puzzle the scientific community. Recent evidence points to epigenetic and chromatin state of the genome to have an important role. Methods: 355 healthy young individuals were genotyped for 52 known obesity-associated SNPs and we obtained DNA methylation levels in their blood using the Illumina 450K BeadChip. Associations between alleles and methylation at proximal cytosine residues were tested using a linear model adjusted for age, sex, weight category and a proxy for blood cell type counts. For replication in other tissues, we used two open-access datasets (skin fibroblasts, n=62; four brain regions, n=121-133) and an additional dataset in subcutaneous and visceral fat (n=149). Results: We found that alleles at 28 of these obesity-associated SNPs associate with methylation levels at 107 proximal CpG sites. Out of 107 CpG sites, 38 are located in gene promoters, including genes strongly implicated in obesity (MIR148A, BDNF, PTPMT1, NR1H3, MGAT1, SCGB3A1, HOXC12, PMAIP1, PSIP1, RPS10-NUDT3, RPS10, SKOR1, MAP2K5, SIX5, AGRN, IMMP1L, ELP4, ITIH4, SEMA3G, POMC, ADCY3, SSPN, LGR4, TUFM, MIR4721, SULT1A1, SULT1A2, APOBR, CLN3, SPNS1,SH2B1, ATXN2L, and IL27). Interestingly, the associated SNPs are in known eQTLs for some of these genes. We also found that the 107 CpGs are enriched in enhancers in peripheral blood mononuclear cells. Finally, our results indicate that some of these associations are not be blood-specific as we successfully replicated four associations in skin fibroblasts. Conclusions: Our results strongly suggest that many obesity-associated SNPs are associated with proximal gene regulation, which was reflected by association of obesity risk allele genotypes with differential DNA methylation. This study highlights the importance of DNA methylation and other chromatin marks as a way to understand the molecular basis of genetic variants associated to human diseases and traits. Bisulphite converted DNA from 355 individuals aged 14-34 were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.
2015-09-17 | E-GEOD-73103 | biostudies-arrayexpress
Project description:In this study, we used Illumina Infinium HumanMethylation450 Beadchips to compare DNA methylation profiles in blood from 10 pairs of MZ twins and 8 individuals recruited at 0, 3, 6, and 9 months. MZ Group (Group A) contained 10 pairs of MZ twins ranging from 23 to 74 years old, including 8 female and 12 male subjects.Longitudinal study group (Group B) included a pair of MZ (male) twins and 6 unrelated individuals (3 male, 3 female), aged from 24 to 39. Except subject H, all participants in Longitudinal study group (Group B) were recalled every 3 months for 9 months (0, 3, 6, and 9 m). Subject H was studied only at 0, 6, and 9 months. Bisulphite converted DNA from the 60 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2013-10-30 | E-GEOD-51388 | biostudies-arrayexpress
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2010-07-31 | E-GEOD-15826 | biostudies-arrayexpress
Project description:Confounding due to cellular heterogeneity represents one of the foremost challenges currently facing Epigenome-Wide Association Studies (EWAS). Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogeneous biospecimens such as whole blood, offer a promising solution. However, their performance depends entirely on the library of DNA methylation markers being used as the basis for deconvolution. The objective of this study was to train and validate an algorithm for the identification of optimal DNA methylation libraries for the deconvolution of adult human whole blood. Purified granulocytes, monocytes, CD4T, CD8T, natural killer cells, and B cells from normal human subjects were purchased from AllCells LLC (Emeryville, CA). DNA extracted from purified leukocyte subtypes were mixed in predetermined proportions to reconstruct two distinct sets of white blood cell (WBC) mixtures, each consisting of six samples. An additional six whole blood (WB) samples from disease-free adult donors with available immune cell profiling data from flow cytometry were purchased from All-Cells LLC and were included in this investigation. All DNA samples were bisulfite modified using the Zymo EZ DNA Methylation kit (Irvine, CA) and profiled for DNA methylation using the Illumina HumanMethylation450 array platform.
2016-02-12 | E-GEOD-77797 | biostudies-arrayexpress