Generation of a genomic tiling array of the human major histocompatibility complex (MHC) and its application for DNA methylation analysis.
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.


CONCLUSIONS
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.
Tomazou
Eleni M
EM
The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. emt@sanger.ac.uk
Rakyan
Vardhman K
VK
Lefebvre
Gregory
G
Andrews
Robert
R
Ellis
Peter
P
Jackson
David K
DK
Langford
Cordelia
C
Francis
Matthew D
MD
Bäckdahl
Liselotte
L
Miretti
Marcos
M
Coggill
Penny
P
Ottaviani
Diego
D
Sheer
Denise
D
Murrell
Adele
A
Beck
Stephan
S