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

Tomazou, EM; Rakyan, VK; Lefebvre, G; Andrews, R; Ellis, P; Jackson, DK; Langford, C; ... Beck, S; + view all (2008) Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis. BMC Medical Genomics , 1 , Article 19. 10.1186/1755-8794-1-19. Green open access

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[thumbnail of Additional file 1:  Scatter-plots of control hybridizations using the MHC tiling array. a). Comparison of biological replicates; b). Comparison of biological replicates after LM-PCR; c). Comparison of profiles with and without LM-PCR; d). Comparison of dy]
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Other (Additional file 1: Scatter-plots of control hybridizations using the MHC tiling array. a). Comparison of biological replicates; b). Comparison of biological replicates after LM-PCR; c). Comparison of profiles with and without LM-PCR; d). Comparison of dy)
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[thumbnail of Additional file 2:  tDMRs within the MHC region. A total of 90 tDMRs were identified. Six pair-wise comparisons were performed and, in total, 90 tDMRs were identified using t-statistics (see Methods). tDMRs of each comparison and their co-ordinates on chr] Excel Spreadsheet (Additional file 2: tDMRs within the MHC region. A total of 90 tDMRs were identified. Six pair-wise comparisons were performed and, in total, 90 tDMRs were identified using t-statistics (see Methods). tDMRs of each comparison and their co-ordinates on chr)
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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.

Type: Article
Title: Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1755-8794-1-19
Publisher version: http://dx.doi.org/10.1186/1755-8794-1-19
Language: English
Additional information: © 2008 Tomazou et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Extended human MHC, Autoimmune-disease, Copy number, Cells, Hla, Genes, Sites, Expression, Proteins, Identify
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/112689
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