Abstract
The major histocompatibility complex (MHC) on chromosome 6 is one of the most intensively studied regions of the human genome and has many features which make it unique. It is the source of much research interest because of its role in autoimmune and infectious disease susceptibility, and of diagnostic interest because of its role in transplantation and rejection. It is the most gene-dense and SNP-rich region of the genome, with large number of complex haplotypes and other features which must be taken into account when analysing the MHC in the laboratory. This article provides a brief overview of the MHC highlighting some of the issues that must be considered when developing new methods and assays.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Trowsdale J (2011) The MHC, disease and selection. Immunol Lett. doi:10.1016/j.imlet. 2011.01.002
Shiina T, Hosomichi K, Inoko H et al (2009) The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54:15–39
The MHC Sequencing Consortium (1999) Complete structure and gene map of a major histocompatibility complex (MHC). Nature 401:921–923
Marsh SG, Albert ED, Bodmer WF et al (2010) Nomenclature for factors of the HLA system. Tissue Antigens 75:291–455
Horton R, Gibson R, Coggill P et al (2008) Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics 60:1–18
de Bakker PI, McVean G, Sabeti PC et al (2006) A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nat Genet 38:1166–1172
Smith LK, Sayer DC, Whidborne RS et al (2007) Sequencing-based typing identifies novel alleles due to single nucleotide polymorphisms in ‘conserved’ regions. Tissue Antigens 69(suppl 1):56–57
Choy MK, Phipps ME (2010) MICA polymorphism: biology and importance in immunity and disease. Trends Mol Med 16:97–106
Posch PE, Cruz I, Bradshaw D et al (2003) Novel polymorphisms and the definition of promoter ‘alleles’ of the tumour necrosis factor and lymphotoxin alpha loci: inclusion in HLA haplotypes. Genes Immun 4:547–558
Smith WP, Vu Q, Li SS et al (2006) Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes. Genomics 87:561–571
Stewart CA, Horton R, Allcock RJ et al (2004) Complete MHC haplotype sequencing for common disease gene mapping. Genome Res 14:1176–1187
Degli-Esposti MA, Leaver AL, Christiansen FT et al (1992) Ancestral haplotypes: conserved population MHC haplotypes. Hum Immunol 34:242–252
Allcock RJN, Windsor L, Gut IG et al (2004) High-density SNP genotyping defines 17 Âdistinct haplotypes of the TNF block in the Caucasian population: implications for haplotype tagging. Hum Mutat 24:517–525
Valente FP, Tan CR, Temple SE et al (2009) The evolution and diversity of TNF block haplotypes in European, Asian and Australian Aboriginal populations. Genes Immun 10:607–615
Yang Z, Yu CY (2000) Organisations and gene duplications of the human and mouse MHC complement gene clusters. J Exp Med 191:2183–2196
Traherne JA, Horton R, Roberts AN et al (2006) Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history. PLoS Genet 2:e9
Erlich RL, Jia X, Anderson S et al (2011) Next-generation sequencing for HLA-typing of class I loci. BMC Genomics 12:42–55
Tomazou EM, Rakyan VK, Lefebvre G et al (2008) Generation of a genomic tiling array of the human major histocompatibility complex (MHC) and its application for DNA methylation analysis. BMC Med Genomics 1:19
Acknowledgements
I am grateful to Winthrop Professor Frank Christiansen for his critical comments and suggestions during the preparation of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Allcock, R.J.N. (2012). The Major Histocompatibility Complex: A Paradigm for Studies of the Human Genome. In: Christiansen, F., Tait, B. (eds) Immunogenetics. Methods in Molecular Biology, vol 882. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-842-9_1
Download citation
DOI: https://doi.org/10.1007/978-1-61779-842-9_1
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-841-2
Online ISBN: 978-1-61779-842-9
eBook Packages: Springer Protocols