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DNA methylation data from Reduced Representation Bisulphite sequencing in the Dutch Hunger Winter Families Study

ABSTRACT: We report on genome-wide DNA methylation differences associated with early gestational famine exposure. We find that open chromatin regions and enhancers are especially sensitive to prenatal famine exposure.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54983 | GEO | 2014/07/01

SECONDARY ACCESSION(S): PRJNA238209

REPOSITORIES: GEO

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DNA methylation data from Reduced Representation Bisulphite sequencing in the Dutch Hunger Winter Families Study

Project description:We report on genome-wide DNA methylation differences associated with early gestational famine exposure. We find that open chromatin regions and enhancers are especially sensitive to prenatal famine exposure. We compared 24 individuals conceived during the Dutch Famine, a brief 6 month famine at the end of WWII, with a same sex sibling.

2014-07-01 | E-GEOD-54983 | biostudies-arrayexpress

LUMC-CU access committee Dutch Hunger Winter Families Study

Project description:Data Access Committee EGAC00001000155

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DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood

Project description:Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis. DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing β cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-term metabolic health. The specific mechanism awaits elucidation.

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PyMT 4 stages tumor progression ERRBS (Enhanced Reduced Representation Bisulphite Sequencing )

Project description:We sequenced mammary tissues of PyMT mice from 4 stages (hyperplasia at week 6, adenoma/MIN at week 8, early carcinoma at week 10, and late carcinoma at week 12) during tumor progression. We also sequenced mammary tissues of age-matched FVB controls.

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Reduced Representation Bisulphite Sequencing of WT and AICDA KO iPCS clones

Project description:We report AICDA facilitates naïve pluripotency of mouse iPSCs by suppressing FGF/ERK signaling. In the absence of AICDA iPSCs fail to achive naïve pluripotent state and display chracteristics of EpiSCs and are primed for differentiation.

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Reduced representation bisulphite sequencing of ten bovine somatic tissues reveals DNA methylation patterns and their impacts on gene expression.

Project description:BackgroundAs a major epigenetic component, DNA methylation plays important functions in individual development and various diseases. DNA methylation has been well studied in human and model organisms, but only limited data exist in economically important animals like cattle.ResultsUsing reduced representation bisulphite sequencing (RRBS), we obtained single-base-resolution maps of bovine DNA methylation from ten somatic tissues. In total, we evaluated 1,868,049 cytosines in CG-enriched regions. While we found slightly low methylation levels (29.87 to 38.06 %) in cattle, the methylation contexts (CGs and non-CGs) of cattle showed similar methylation patterns to other species. Non-CG methylation was detected but methylation levels in somatic tissues were significantly lower than in pluripotent cells. To study the potential function of the methylation, we detected 10,794 differentially methylated cytosines (DMCs) and 836 differentially methylated CG islands (DMIs). Further analyses in the same tissues revealed many DMCs (including non-CGs) and DMIs, which were highly correlated with the expression of genes involved in tissue development.ConclusionsIn summary, our study provides a baseline dataset and essential information for DNA methylation profiles of cattle.

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Project description:In the clinical management of paediatric solid tumours, histological examination of tumour tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumour is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumour samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of paediatric tumours using cell-free reduced representation bisulphite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumour type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in paediatric oncology in a cost-effective and minimally invasive manner.

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Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (CHINFAM Data Set)

Project description:Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation we exposed human fibroblasts to nutritional deprivation. In the famine exposed schizophrenia patients we found significant hypermethylation of the dual specificity phosphatase 22 (DUSP22) gene promoter (Chr6:291687-293285) (N=153, p=0.01). In this sample DUSP22 methylation was also significantly higher in patients independent of famine exposure (p=0.025), suggesting that hypermethylation of DUSP22 is also more generally involved in schizophrenia risk. Similarly, DUSP22 methylation was also higher in two separate case-control sample not exposed to famine using DNA from whole blood (N=64, p=0.03) and postmortem brains (N=214, p=0.007). DUSP22 methylation showed strong genetic regulation across chromosomes by a region on chromosome 16 which was consistent with new 3D genome interaction data. The presence of a direct link between famine and DUSP22 transcription was supported by data from cultured human fibroblasts that showed increased methylation (p=0.048) and expression (p=0.019) in response to nutritional deprivation (N=10). These results highlight a first epigenetic locus that is genetically regulated across chromosomes and that is involved in the response to early life exposure to famine and that is relevant for a major psychiatric disorder.

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Genetic vulnerability to DUSP22 promotor hypermethylation is involved in the relation between in utero famine exposure and schizophrenia (DUTCHSCZ Data Set)

2018-06-29 | GSE116378 | GEO