Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The evolution and diversity of TNF block haplotypes in European, Asian and Australian Aboriginal populations

Genes & Immunity volume 10, pages 607–615 (2009)Cite this article

Abstract

The region spanning the tumour necrosis factor (TNF) cluster in the human major histocompatibility complex is implicated in susceptibility to immunopathological disease, but ethnic differences and linkage disequilibrium have hampered identification of critical polymorphisms. Here, we investigate Europeans, Asians (Bidayuh, Chinese, Indian, Jehai, Malay, Temuan) and Australian Aborigines to provide a framework for disease-association studies. DNA from 999 unrelated healthy donors was genotyped at 38 loci, primarily in coding and promoter regions over a 60-kb region spanning seven genes near TNF. The PHASE algorithm was used to statistically infer TNF block haplotypes and estimate their frequencies in each population. The TNF block is carried as 31 haplotypes in all populations combined, with <19 in any single population. Only six haplotypes have a unique tag single nucleotide polymorphism (SNP) valid for all populations, but seven haplotypes could be tagged with individual SNPs in selected populations. Four to eight TNF block haplotypes exist across all ethnicities, and hence must pre-date the divergence of these populations from a common ancestor >160 000 years ago. Some haplotypes are unique to isolated populations, but they do not contain unique SNP. Hence, they reflect restricted migration and/or extinction of some families rather than de novo mutation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 3
Figure 2
Figure 4

Similar content being viewed by others

References

  1. Price P, Witt C, Allcock RJN, Sayer D, Garlepp M, Kok CC et al. The genetic basis for the association of the 8.1 ancestral haplotype with multiple immunopathological diseases. Immunol Rev 1999; 167: 257–274.

    Article  CAS  Google Scholar 

  2. Ackerman HC, Ribas G, Jallow M, Mott R, Neville M, Sisay-Joof F et al. Complex haplotypic structure of the central MHC region flanking TNF in a West African population. Genes Immun 2003; 4: 476–486.

    Article  CAS  Google Scholar 

  3. Allcock RJN, Windsor L, Gut IG, Kucharzak R, Sobre L, Lechner D et al. High-density SNP genotyping defines 17 distinct haplotypes of the TNF block in the Caucasian population: implications for haplotypes tagging. Hum Mutat 2004; 24: 517–525.

    Article  CAS  Google Scholar 

  4. Jinam TA, Phipps ME, Indran M, Kuppusamy UR, Mahmood AA, Hong LC et al. An update of the general health status in the indigenous populations of Malaysia. Ethn Health 2008; 13: 277–287.

    Article  Google Scholar 

  5. Oppenheimer S . Out of Eden: the peopling of the world, Constable, London. Republished as: The real Eve: modern man's journey out of Africa, Carroll & Graf New York, 2003.

  6. Gaudieri S, Leelayuwat C, Tay GK, Townend DC, Dawkins RL . The major histocompatibility complex (MHC) contains conserved polymorphic genomic sequences that are shuffled by recombination to form ethnic-specific haplotypes. J Mol Evol 1997; 45: 17–23.

    Article  CAS  Google Scholar 

  7. Basu A, Mukherjee N, Roy S, Sengupta S, Banerjee S, Chakraborty M et al. Ethnic India: a genomic view, with special reference to peopling and structure. Genome Res 2003; 13: 2277–2290.

    Article  CAS  Google Scholar 

  8. Redd AJ, Stoneking M . Peopling of sahul: mtDNA variation in Aboriginal Australian and Papua New Guinean populations. Am J Hum Genet 1999; 65: 808–828.

    Article  CAS  Google Scholar 

  9. Redd AJ, Roberts-Thomson J, Karafet T, Bamshad M, Jorde LB, Naidu JM et al. Gene flow from the Indian subcontinent to Australia: evidence from the Y chromosome. Curr Biol 2002; 12: 673–677.

    Article  CAS  Google Scholar 

  10. Bayley J-P, Ottenhoff THM, Verweij CL . Is there a future for TNF promoter polymorphisms? Genes Immun 2004; 5: 315–329.

    Article  CAS  Google Scholar 

  11. Price P, Morahan G, Allcock RJN, Sayer D, Garlepp M, Kok CC et al. Polymorphism in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases. AIDS 2002; 16: 2043–2047.

    Article  CAS  Google Scholar 

  12. Okamoto K, Makino S, Yoshikawa Y, Takaki A, Nagatsuka Y, Ota M et al. Identification of Iκbl as the second major histocompatibility complex-linked susceptibility locus for rheumatoid arthritis. Am J Hum Genet 2003; 72: 303–312.

    Article  CAS  Google Scholar 

  13. Valente FP, Tan CRT, Phipps M, Witt CS, Kaur G, Gut I et al. TNF block haplotypes associated with conserved MHC haplotypes in European, Asian and Australian Aboriginal donors. Tissue Antigens (e-pub ahead of print, April 2009; doi:10.1111/j.1399-0039.2009.01258).

  14. Raymond M, Rousset F . GENEPOP (version 1.2): population genetics software for exact tests and ecumenicism. J Hered 1995; 86: 248–249.

    Article  Google Scholar 

  15. Stephens M, Smith NJ, Donnelly P . A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978–989.

    Article  CAS  Google Scholar 

  16. Stephens M, Donnelly P . A comparison of Bayesian methods for haplotypes reconstruction from population data. Am J Hum Genet 2003; 73: 1162–1169.

    Article  CAS  Google Scholar 

  17. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H . ClustalW2 and ClustalX version 2.0. Bioinformatics 2007; 23: 2947–2948.

    Article  CAS  Google Scholar 

  18. Felsenstein J . PHYLIP, phylogeny inference package (version 3.2). Cladistics 1989; 5: 164–166.

    Google Scholar 

  19. Perrière G, Gouy M . WWW-Query: an on-line retrieval system for biological sequence banks. Biochimie 1996; 78: 364–369.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Steven Roberts for assistance with assembly of the sample banks, the Australian Bone Marrow Donor Registry of Western Australia, the staff of the Centre National de Génotypage for genotyping, Jean Francois Zagury, Cedric Coulonges, Oliver Delaneau and Sophie Limou for their advice and Lieng Taing for his SNP map software. This is publication 2008-31 (Clinical Immunology and Immunogenetics, RPH).

Author information

Authors and Affiliations

  1. School of Bioinformatics, University of Paris Diderot, Paris, France

    F P Valente

  2. School of Pathology and Laboratory Medicine, University of Western Australia, Western Australia, Australia

    F P Valente, C R T Tan, R J N Allcock, C S N Chew & P Price

  3. School of Medicine and Pharmacology, University of Western Australia, Western Australia, Australia

    S E Temple

  4. University of Malaya, Kuala Lumpur, Malaysia

    M Phipps

  5. Clinical Immunology and Immunogenetics, Royal Perth Hospital, Western Australia, Australia

    C S Witt

  6. Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India

    G Kaur

  7. Centre National de Génotypage, Evry, France

    I Gut & S McGinn

Authors
  1. F P Valente
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C R T Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S E Temple
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Phipps
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C S Witt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I Gut
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S McGinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R J N Allcock
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C S N Chew
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P Price
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Price.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valente, F., Tan, C., Temple, S. et al. The evolution and diversity of TNF block haplotypes in European, Asian and Australian Aboriginal populations. Genes Immun 10, 607–615 (2009). https://doi.org/10.1038/gene.2009.45

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2009.45

Keywords

This article is cited by

Search

Advanced search

Quick links