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

被引：26

作者：

Tomazou, Eleni M. ^{[2
]}

Rakyan, Vardhman K. ^{[3
]}

Lefebvre, Gregory ^{[2
]}

Andrews, Robert ^{[2
]}

Ellis, Peter ^{[2
]}

Jackson, David K. ^{[2
]}

Langford, Cordelia ^{[2
]}

Francis, Matthew D. ^{[2
]}

Baeckdahl, Liselotte ^{[1
]}

Miretti, Marcos ^{[2
]}

Coggill, Penny ^{[2
]}

Ottaviani, Diego ^{[3
,5
]}

Sheer, Denise ^{[3
]}

Murrell, Adele ^{[4
]}

Beck, Stephan ^{[1
]}

机构：

[1] UCL, Inst Canc, London WC1E 6BT, England

[2] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[3] Barts & London Queen Marys Sch Med & Dent, Inst Cell & Mol Sci, London E1 2AT, England

[4] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England

[5] Canc Res UK London Res Inst, London WC2A 3PX, England

来源：

BMC MEDICAL GENOMICS | 2008年 / 1卷 / 1期

基金：

英国惠康基金; 澳大利亚国家健康与医学研究理事会;

关键词：

D O I：

10.1186/1755-8794-1-19

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：16

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