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PLoS Biol. 2004 Dec;2(12):e405. Epub 2004 Nov 23.

DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project.

Author information

1
The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

Abstract

The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data.

PMID:
15550986
PMCID:
PMC529316
DOI:
10.1371/journal.pbio.0020405
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

JL, KB, TH, TO, and AO are employees of Epigenomics AG. IGG and SB are members of the scientific advisory board of Epigenomics AG, but do not benefit financially from their involvement in this study. Epigenomics AG has filed for patents based on some of the work described here. Epigenomics AG was a scientific collaborator in the study. The work described here was funded by a grant from the European Union Framework 5 Programme.

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