Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation

ABSTRACT: To assess variation and inheritance of genome-wide patterns of DNA methylation simultaneously in humans, we applied reduced representation bisulfite sequencing (RRBS) to somatic DNA from six members of a three-generation family. Reduced representation bisulfite sequencing was applied to genomic DNA from leukocytes of 6 family members and two unrelated individuals.

ORGANISM(S): Homo sapiens

SUBMITTER: Jason Gertz

PROVIDER: E-GEOD-30253 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation.

Gertz Jason J Varley Katherine E KE Reddy Timothy E TE Bowling Kevin M KM Pauli Florencia F Parker Stephanie L SL Kucera Katerina S KS Willard Huntington F HF Myers Richard M RM

PLoS genetics 20110811 8

The methylation of cytosines in CpG dinucleotides is essential for cellular differentiation and the progression of many cancers, and it plays an important role in gametic imprinting. To assess variation and inheritance of genome-wide patterns of DNA methylation simultaneously in humans, we applied reduced representation bisulfite sequencing (RRBS) to somatic DNA from six members of a three-generation family. We observed that 8.1% of heterozygous SNPs are associated with differential methylation ...[more]

PMID: 21852959

Similar Datasets

Laser Capture Microdissection-Reduced Representation Bisulfite Sequencing (LCM-RRBS) maps changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse

Project description:DNA methylation is a mechanism for long-term transcriptional regulation and is required for normal cellular differentiation. Failure to properly establish or maintain DNA methylation patterns leads to cell dysfunction and diseases such as cancer. Identifying DNA methylation signatures in complex tissues can be challenging due to inaccurate cell enrichment methods and low DNA yields. We have developed a technique called Laser Capture Microdissection-Reduced Representation Bisulfite Sequencing (LCM-RRBS) for the multiplexed interrogation of the DNA methylation status of CpG Islands and promoters. LCM-RRBS accurately and reproducibly profiles genome-wide methylation of DNA extracted from microdissected fresh frozen or formalin-fixed paraffin-embedded tissue samples. To demonstrate the utility of LCM-RRBS, we characterized changes in DNA methylation associated with gonadectomy-induced adrenocortical neoplasia in the mouse. Compared to adjacent normal tissue, the adrenocortical tumors showed reproducible gains and losses of DNA methylation at genes involved in cell differentiation and organ development. LCM-RRBS is a rapid, cost-effective, and sensitive technique for analyzing DNA methylation in heterogeneous tissues and will facilitate the investigation of DNA methylation in cancer and organ development. Laser capture microdissection-reduced representation bisulfite sequencing and reduced representation bisulfite sequencing on human blood leukocyte, human endometrial tumor, mouse liver tissue, and mouse normal and neoplastic adrenal tissue

2013-03-21 | E-GEOD-45361 | biostudies-arrayexpress

Genome-scale DNA methylation maps of pluripotent and differentiated cells

Project description:We report the generation and analysis of genome-scale DNA methylation profiles at nucleotide resolution in mammalian cells. Using high-throughput Reduced Representation Bisulfite Sequencing (RRBS) and single-molecule-based sequencing, we generated DNA methylation maps covering the vast majority of CpG islands, and a representative sampling of conserved non-coding elements, transposons and other genomic features, for murine embryonic stem (ES) cells, ES-derived and primary neural cells, and eight other primary tissues. Several key findings emerge from the data. First, DNA methylation patterns are better correlated with histone methylation patterns than with the underlying genome sequence context. Second, methylation of CpGs are dynamic epigenetic marks that undergo extensive changes during cellular differentiation, particularly in regulatory regions outside of core promoters. Third, analysis of ES-derived and primary cells reveals that 'weak' CpG islands associated with a specific set of developmentally regulated genes undergo aberrant hypermethylation during extended proliferation in vitro, in a pattern reminiscent of that reported in some primary tumors. More generally, the results establish RRBS as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine. Keywords: High-throughput Reduced Representation Bisulfite Sequencing (RRBS), Illumina, cell type comparison Reduced representation bisulfite sequencing (MspI,~40-220bp size fraction) of 18 murine cell types. Raw sequence data files for this study are available for download from the SRA FTP site at ftp://ftp.ncbi.nlm.nih.gov/sra/Studies/SRP000/SRP000179

2008-07-06 | E-GEOD-11034 | biostudies-arrayexpress

Methylation profiling by array of 108 clear cell renal cell carcinoma

Project description:A Cartes d'Identite des Tumeurs (CIT) project from the French Ligue Nationale Contre le Cancer (<a href=\\ttp://cit.ligue-cancer.net/\\ target=\\_blank\\>http://cit.ligue-cancer.net</a>). Selecting patients with metastatic clear-cell renal cell carcinoma (m-ccRCC) who might benefit from treatment with targeted tyrosine kinase inhibitors (TKIs) is a challenge. Our aim was to identify molecular markers associated with outcome in m-ccRCC patients treated with sunitinib.\

2016-02-26 | E-MTAB-3274 | biostudies-arrayexpress

Methylation data as part of an Integrated analysis of oligodendroglial tumours

Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net: Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished based on the IDH mutation and the 1p/19q co-deletion. Here we performed an integrated analysis of the transcriptome, genome and methylome of 156 OT. Beyond the 3 well-known molecular classes, our multi-omics classification revealed 3 subgroups within 1p/19q co-deleted tumours, associated with different expression patterns of oligodendroglial progenitor cell (OPC), astrocytic, oligodendrocytic and neuronal lineage genes. The validity of these 3 subgroups was confirmed on public datasets. The OPC-like group was associated with a more aggressive histological and genomic profile and with MYC activation that occurred through various alterations including MYC locus genomic gain, MYC exon 3 hypo-methylation and down-regulation of microRNA-34b/c. In the lower grade glioma TCGA dataset, the OPC-like group was associated with a poorer outcome independently from histological grade. Our study unravels previously unrecognized heterogeneity among 1p/19q co-deleted tumours.

2016-03-11 | E-MTAB-3903 | biostudies-arrayexpress

Recurrent TCF12 mutations in anaplastic oligodendroglioma

Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net: Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable with few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome and/or transcriptome sequencing identifying previously reported frequent somatic mutations in CIC and FUBP1 genes. We also identified recurrent mutations in TCF12 (11% of IDHmut-codel) which encodes basic helix-loop-helix (bHLFH) transcription factor 12 which is an oligodendrocyte-related transcription factor in IDHmut-codel tumors. Strikingly, the somatic mutations (encoding E548R and R602M substitutions) have not been reported previously in cancer but are identical to germline mutations causing craniosynostosis. Incorporating TCGA data on 43 AO tumors also implicates functional mutation of SMARCA4, NOTCH1, NOTCH2, SETD2, RBPJ and ARID1A/1B. These data are compatible with the combined deregulation of metabolism, chromatin organization/remodeling and Notch-pathway genes in AO oncogenesis. Our analysis provides further insights into the unique and shared pathways driving AO and new targets for therapeutic intervention.

2015-06-15 | E-MTAB-2767 | biostudies-arrayexpress

Methylation profiling by array of cartilage tumors

Project description:In this study, a series of 102 cartilage tumors was used to uncover the molecular diversity of chondrosarcomas through the profiling of mRNA, miRNA, DNA methylation, DNA copy number aberrations and point mutations. An integrated classification using multiple molecular dimensions revealed three major molecular features unraveling the diversity in clinical outcome of chondrosarcoma: a high mitotic state, regional 14q32 loss of expression and IDH mutations leading to genome-wide hypermethylation. These three robust and simple molecular features classify chondrosarcoma in subtypes with superior clinical value as compared to the current grading system.

2019-07-19 | E-MTAB-7263 | biostudies-arrayexpress

Methylation profiling by array of pancreatic adenocarcinoma (PDAC) xenografts

Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. the variable MultiOmicsClassification indicates the resulting sample's group. Whole-genome DNA methylation was analyzed using the Illumina Infinium HumanMethylation450 Beadchips. Integragen SA (Evry, France) carried out microarray experiments and hybridized to the BeadChip arrays following the manufacturer’s instructions. Illumina GenomeStudio software was used to extract the beta value DNA methylation score for each locus. We removed data from probes that contained SNPs or overlapped with a repetitive element that was not uniquely aligned to the human genome or regions of insertions and deletions in the human genome. The CpG Island Methylator Phenotype (CIMP) index was determined using methylation Illumina Infinium HumanMethylation450 BeadChips based on previous low throughput work (Toyota, 1999). In brief, all island CpG found to be unmethylated (<20% Beta-value) in all 25 normal pancreatic samples from the ICGC consortium (Nones, 2014) were selected. The CIMP index was calculated independently for each sample as the proportion of methylated (>30% Beta-value) CpGs among the selected normally unmethylated island CpG.

2017-12-12 | E-MTAB-5008 | biostudies-arrayexpress

Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis (eRRBS)

Project description:DNA methylation is tightly regulated throughout mammalian development and altered methylation patterns are a hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in acute myeloid leukemia (AML) and has been suggested to protect CpG islands and promoters from aberrant methylation. By generating a novel mouse model of Tet2-deficient AML we show that loss of Tet2 in hematopoietic cells leads to progressive hypermethylation of active enhancer elements and altered expression of genes implicated in tumorigenesis. In contrast, CpG island and promoter methylation does not change in a Tet2-dependent manner. Furthermore, we confirm this specific enhancer hypermethylation phenotype in human AML patients. Thus, we propose that TET2 prevents leukemic transformation of hematopoietic cells by protecting enhancers from aberrant DNA methylation. Enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analysis of in vitro-grown hematopoietic cells transduced with AML1-ETO or MLL-AF9

2015-04-22 | E-GEOD-59584 | biostudies-arrayexpress

Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [mRRBS]

Project description:Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Mammary glands were collected from mice at non-pregnant and pregnant stages for DNA extraction and DNA methylation analysis via mRRBS (multiplexed reduced representation bisulfite sequencing).

2015-01-22 | E-GEOD-54149 | biostudies-arrayexpress

Local DNA hypomethylation activates genes in rice endosperm

Project description:Cytosine methylation silences transposable elements in plants, vertebrates and fungi, but also regulates gene expression1. Plant methylation is catalyzed by three families of enzymes, each with a preferred sequence context: CG, CHG (H = A, C or T) and CHH, with CHH methylation targeted by the RNA interference (RNAi) pathway2. Arabidopsis thaliana endosperm, a placenta-like tissue that nourishes the embryo, is globally hypomethylated in the CG context while retaining high non-CG methylation3. Global methylation dynamics in seeds of cereal crops that provide the bulk of human nutrition remain unknown. Here we show that rice endosperm DNA is hypomethylated in all sequence contexts. Non-CG methylation is reduced evenly across the genome, while CG hypomethylation is localized. CHH methylation of small transposable elements is increased in embryos, suggesting that endosperm demethylation enhances transposon silencing. Genes preferentially expressed in endosperm, including those coding for major storage proteins and starch synthesizing enzymes, are frequently hypomethylated in endosperm, indicating that DNA methylation is a crucial regulator of rice endosperm biogenesis. Our data demonstrate that genome-wide reshaping of seed DNA methylation is conserved among angiosperms and has a profound effect on gene expression in cereal crops. Keywords: Epigenetics Examination of DNA methylation in rice

2010-11-01 | E-GEOD-22591 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data