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The Major Histocompatibility Complex: A Paradigm for Studies of the Human Genome

  • Richard J. N. Allcock
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 882)

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.

Key words

Major histocompatibility complex Genetic polymorphism HLA Immune genes 

Notes

Acknowledgements

I am grateful to Winthrop Professor Frank Christiansen for his critical comments and suggestions during the preparation of this manuscript.

References

  1. 1.
    Trowsdale J (2011) The MHC, disease and selection. Immunol Lett. doi: 10.1016/j.imlet. 2011.01.002
  2. 2.
    Shiina T, Hosomichi K, Inoko H et al (2009) The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54:15–39PubMedCrossRefGoogle Scholar
  3. 3.
    The MHC Sequencing Consortium (1999) Complete structure and gene map of a major histocompatibility complex (MHC). Nature 401:921–923CrossRefGoogle Scholar
  4. 4.
    Marsh SG, Albert ED, Bodmer WF et al (2010) Nomenclature for factors of the HLA system. Tissue Antigens 75:291–455PubMedCrossRefGoogle Scholar
  5. 5.
    Horton R, Gibson R, Coggill P et al (2008) Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project. Immunogenetics 60:1–18PubMedCrossRefGoogle Scholar
  6. 6.
    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 38:1166–1172PubMedCrossRefGoogle Scholar
  7. 7.
    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):56–57PubMedCrossRefGoogle Scholar
  8. 8.
    Choy MK, Phipps ME (2010) MICA polymorphism: biology and importance in immunity and disease. Trends Mol Med 16:97–106PubMedCrossRefGoogle Scholar
  9. 9.
    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 4:547–558PubMedCrossRefGoogle Scholar
  10. 10.
    Smith WP, Vu Q, Li SS et al (2006) Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes. Genomics 87:561–571PubMedCrossRefGoogle Scholar
  11. 11.
    Stewart CA, Horton R, Allcock RJ et al (2004) Complete MHC haplotype sequencing for common disease gene mapping. Genome Res 14:1176–1187PubMedCrossRefGoogle Scholar
  12. 12.
    Degli-Esposti MA, Leaver AL, Christiansen FT et al (1992) Ancestral haplotypes: conserved population MHC haplotypes. Hum Immunol 34:242–252PubMedCrossRefGoogle Scholar
  13. 13.
    Allcock RJN, Windsor L, Gut IG et al (2004) High-density SNP genotyping defines 17 ­distinct haplotypes of the TNF block in the Caucasian population: implications for haplotype tagging. Hum Mutat 24:517–525PubMedCrossRefGoogle Scholar
  14. 14.
    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 10:607–615PubMedCrossRefGoogle Scholar
  15. 15.
    Yang Z, Yu CY (2000) Organisations and gene duplications of the human and mouse MHC complement gene clusters. J Exp Med 191:2183–2196CrossRefGoogle Scholar
  16. 16.
    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:e9PubMedCrossRefGoogle Scholar
  17. 17.
    Erlich RL, Jia X, Anderson S et al (2011) Next-generation sequencing for HLA-typing of class I loci. BMC Genomics 12:42–55PubMedCrossRefGoogle Scholar
  18. 18.
    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 1:19PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Lotterywest State Biomedical Facility Genomics, School of Pathology and Laboratory MedicineUniversity of Western AustraliaNedlandsAustralia
  2. 2.Department of Clinical Immunology, PathWest Laboratory MedicineRoyal Perth HospitalPerthAustralia

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