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Open Access Research article

Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis

Eleni M Tomazou1, Vardhman K Rakyan2, Gregory Lefebvre1, Robert Andrews1, Peter Ellis1, David K Jackson1, Cordelia Langford1, Matthew D Francis1, Liselotte Bäckdahl4, Marcos Miretti1, Penny Coggill1, Diego Ottaviani25, Denise Sheer2, Adele Murrell3 and Stephan Beck4*

Author Affiliations

1 The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

2 Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London, E1 2AT, UK

3 Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK

4 UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK

5 Cancer Research UK London Research Institute, Lincoln's Inn Fields, London, WC2A 3PX, UK

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BMC Medical Genomics 2008, 1:19  doi:10.1186/1755-8794-1-19

Published: 30 May 2008

Abstract

Background

The major histocompatibility complex (MHC) is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome.

Methods

To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP), methylated DNA immunoprecipitation (MeDIP), array comparative genomic hybridization (aCGH) and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls.

Results

Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs). Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation.

Conclusion

A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.