Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Methylation profiling by array of subcutaneous fat derived from 856 TwinsUK participants

ABSTRACT: Epigenetic changes such as DNA methylation variation are known to play a role in gene regulation and common disease susceptibility. Little is known about the genome-wide frequency, localization and function of such changes and how they are regulated by genetic and environmental factors. We have utilized the MuTHER resource and generated methylation profiles across multiple tissues conducted in a large set of female individuals that allows systematic dissection of genetic and non-genetic effects on DNA methylation. DNA methylation was quantified in subcutaneous fat and skin derived from 648 TwinsUK participants using the Infinium HumanMethylation450 BeadChips. Data from transcription profiling of skin, adipose fat and lymphoblastoid cell lines (LCLs) from the same set of TwinsUK participants have been deposited in ArrayExpress under accession number E-TABM-1140 (https://www.ebi.ac.uk/arrayexpress/experiments/E-TABM-1140).

ORGANISM(S): Homo sapiens

SUBMITTER: Elin Grundberg

PROVIDER: E-MTAB-1866 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Mapping cis- and trans-regulatory effects across multiple tissues in twins.

Grundberg Elin E Small Kerrin S KS Hedman Åsa K ÅK Nica Alexandra C AC Buil Alfonso A Keildson Sarah S Bell Jordana T JT Yang Tsun-Po TP Meduri Eshwar E Barrett Amy A Nisbett James J Sekowska Magdalena M Wilk Alicja A Shin So-Youn SY Glass Daniel D Travers Mary M Min Josine L JL Ring Sue S Ho Karen K Thorleifsson Gudmar G Kong Augustine A Thorsteindottir Unnur U Ainali Chrysanthi C Dimas Antigone S AS Hassanali Neelam N Ingle Catherine C Knowles David D Krestyaninova Maria M Lowe Christopher E CE Di Meglio Paola P Montgomery Stephen B SB Parts Leopold L Potter Simon S Surdulescu Gabriela G Tsaprouni Loukia L Tsoka Sophia S Bataille Veronique V Durbin Richard R Nestle Frank O FO O'Rahilly Stephen S Soranzo Nicole N Lindgren Cecilia M CM Zondervan Krina T KT Ahmadi Kourosh R KR Schadt Eric E EE Stefansson Kari K Smith George Davey GD McCarthy Mark I MI Deloukas Panos P Dermitzakis Emmanouil T ET Spector Tim D TD

Nature genetics 20120902 10

Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. U ...[more]

PMID: 22941192

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Project description:Serrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5 - 8.7% of CRCs. It has been shown that SAC has a worse prognosis and has different molecular and immunohistochemical features compared to conventional carcinoma (CC) but, to date, there is no study analysing its methylome profile. We have investigated the methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array in 103 colorectal specimens from Spanish and Finnish patients. The comparison between the epigenetic signature of 36 SACs and 34 matched CCs was established with the aim of identifying the functions which characterize SAC biology and also the most differentially methylated genes for subsequent validatation by pyrosequencing, methylation-specific PCR, qPCR and immunohistochemistry, including additional cases. Microarray data showed a higher representation of morphogenesis-, neurogenesis-, cytoskeleton- and vesicle-transport-related functions and also significant differential methylation of 15 genes, including the iodothyronine deiodinase DIO3 and the forkhead family transcription factor FOXD2 genes which were validated at the CpG, mRNA and protein level. A quantification study of the methylation status of CpG sequences in FOXD2 demonstrated a novel region controlling gene expression. Moreover, differences in these markers were also evident when comparing SAC with CRC showing molecular and histological features of high level microsatellite instability. This methylome study demonstrates that SAC has a distinct epigenetic regulation pattern resulting in different biological functions and that DIO3 and FOXD2 might be molecular targets for a specific histology-oriented treatment of CRC. HumanMethylation450K BeadChip (Illumina, Inc, San Diego, CA), using Infinium HD Methylation assay for genome-wide DNA methylation screening, was employed. In brief, genomic DNA (1000 ng) from each sample was bisulfite converted with the EZ DNA Methylation Kit (Zymo Research, Orange, CA) according to the manufacturer´s recommendations. Bisulfite-treated DNA was isothermally amplified at 37°C (20-24h) and the DNA product was fragmented by an endpoint enzymatic process, then precipitated, resuspended, applied to an Infinium Human Methylation450K BeadChip (Illumina, San Diego, CA, USA) and hybridized at 48°C (16-24h). The fluorescently-stained chip was imaged by the Illumina i-SCAN and Illumina's Genome Studio program (Methylation Module) was used to analyze BeadArray data to assign site-specific DNA methylation β-values to each CpG site.

Dataset Information

Methylation profiling by array of subcutaneous fat derived from 856 TwinsUK participants

Publications

Mapping cis- and trans-regulatory effects across multiple tissues in twins.

Similar Datasets

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