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TNF-α promoter single nucleotide polymorphisms are markers of human ancestry

Genes & Immunity volume 3, pages 482–487 (2002)Cite this article

Abstract

We present a map of single nucleotide polymorphisms (SNPs) in the human tumor necrosis factor (TNF)-α promoter based upon exploratory sequencing of 333 human TNF-α gene promoters from individuals of distinct ancestral backgrounds. We detect 10 TNF-α promoter SNPs that occur with distinct frequencies in populations of different ancestry. Consistent with these findings, we show that two TNF-α SNPs, the −243 SNP and the −856 SNP, are the first SNP markers of a sub-Saharan African-derived extended haplotype and an Amerindian HLA haplotype, respectively. Comparisons of TNF-α promoter SNP allele frequencies can thus help elucidate variation of HLA haplotypes and their distribution among existing ethnic groups and shed light into the history of human populations.

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References

  1. Cargill M, Altshuler D, Ireland J et al. Characterization of single-nucleotide polymorphisms in coding regions of human genes Nat Genet 1999 22: 231–238

    Article  CAS  Google Scholar 

  2. Sachidanandam R, Weissman D, Schmidt SC et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms Nat Genet 2001 409: 928–933

    CAS  Google Scholar 

  3. Falvo JV, Uglialoro AM, Brinkman BM et al. Stimulus-specific assembly of enhancer complexes on the tumor necrosis factor alpha gene promoter Mol Cell Biol 2000 20: 2239–2247

    Article  CAS  Google Scholar 

  4. Tsai EY, Falvo JV, Tsytsykova AV et al. A lipopolysaccharide-specific enhancer complex involving ets, elk-1, sp1, and CREB binding protein and p300 is recruited to the tumor necrosis factor alpha promoter in vivo Mol Cell Biol 2000 20: 6084–6094

    Article  CAS  Google Scholar 

  5. Tsytsykova AV, Goldfeld AE . Inducer-specific enhanceosome formation controls TNF-alpha gene expression in T lymphocytes Mol Cell Biol 2002 22: 2620–2631

    Article  CAS  Google Scholar 

  6. Leung JY, McKenzie FE, Uglialoro AM et al. Identification of phylogenetic footprints in primate tumor necrosis factor-alpha promoters Proc Natl Acad Sci USA 2000 97: 6614–6618

    Article  CAS  Google Scholar 

  7. Uglialoro AM, Turbay D, Pesavento PA et al. Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor-alpha gene promoter Tissue Antigens 1998 52: 359–367

    Article  CAS  Google Scholar 

  8. Higuchi T, Seki N, Kamizono S et al. Polymorphism of the 5′ -flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese Tissue Antigens 1998 51: 605–612

    Article  CAS  Google Scholar 

  9. D'Alfonso S, Richiardi PM . A polymorphic variation in a putative regulation box of the TNFA promoter region Immunogenetics 1994 39: 150–154

    CAS  PubMed  Google Scholar 

  10. Zimmerman PA, Guderian RH, Nutman TB . A new TNFA promoter allele identified in South American Blacks Immunogenetics 1996 44: 485–486

    CAS  PubMed  Google Scholar 

  11. Wilson AG, de, Vries N, Pociot F, di, Giovine FS, van, der, Putte LBA, Duff GW . An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles J Exp Med 1993 177: 557−560

    Article  Google Scholar 

  12. Brinkman BM, Kaijzel EL, Huizinga TW, Giphart MJ, Breedveld FC, Verweij CL . Detection of a C-insertion polymorphism within the human tumor necrosis factor alpha (TNFA) gene Hum Genet 1995 96: 493

    Article  CAS  Google Scholar 

  13. Hamann A, Mantzoros C, Vidal-Puig A, Flier JS . Genetic variability in the TNF-alpha promoter is not associated with type II diabetes mellitus (NIDDM) Biochem Biophys Res Commun 1995 211: 833–839

    Article  CAS  Google Scholar 

  14. Hammond MG, du, Toil ED, Sanchez-Mazas A et al. HLA in sub-Saharan Africa: 12th International Histocompatibility Workshop SSAF report. In: Charron D (ed) Genetic Diversity of HLA, Functional and Medical Implication EDK: Paris 1997

    Google Scholar 

  15. Uko GP, Lu LY, Asuquo MA et al. HLA-DRB1 leprogenic motifs in Nigerian population groups Clin Exp Immunol 1999 118: 56–62

    Article  CAS  Google Scholar 

  16. Sullivan AD, Nyircnda T, Cullinan T, Taylor T, Harlow SD, James SA, Meshnick SR . Malaria infection during pregnancy: intrauterine growth retardation and preterm delivery in Malawi J Infect Dis 1999 179: 1580–1583

    Article  CAS  Google Scholar 

  17. Clavijo OP, Delgado JC, Yu N, Fraser PA, Yunis EJ . HLA-Cw*1701 is associated with two sub-Saharan African-derived HLA haplotypes: HLA-B*4201, DRB1*03 and HLA-B*4202 without DRB1*03 Tissue Antigens 1999 54: 303–306

    Article  CAS  Google Scholar 

  18. Vigilant LSM, Harpending H, Hawkes K, Wilson AC . African populations and the evolution of human mitochondrial DNA Science 1991 253: 1503–1507

    Article  CAS  Google Scholar 

  19. Templeton A . Out of Africa again and again Nature 2002 416: 45–51

    Article  CAS  Google Scholar 

  20. Yunis JJ, Mobini N, Yunis EJ et al. Common major histocompatibility complex class II markers in clinical variants of cicatricial pemphigoid Proc Natl Acad Sci USA 1994 91: 7747–7751

    Article  CAS  Google Scholar 

  21. Yu N, Ohashi M, Alosco S et al. Typing of HLA-B*15 alleles using sequence-specific primers Tissue Antigens 1998 52: 260–269

    Article  CAS  Google Scholar 

  22. Lazaro AM, Marcos CY, Fernandez-Vina MA, Moraes ME, Moraes JR, Stastny P . Brazilian Terena Normal In: Gjertson DW, Terasaki PI (eds) HLA 1998 American Society for Histocompatibility and Immunogenetics: Lenexa, KS 1998

    Google Scholar 

  23. Layrisse Z, Guedez Y, Dominguez E et al. Extended HLA haplotypes in a Carib Amerindian population: the Yucpa of the Perija Range Hum Immunol 2001 62: 992–1000

    Article  CAS  Google Scholar 

  24. Lin M, Chu CC, Lee HL et al. Heterogeneity of Taiwan's indigenous population: possible relation to prehistoric Mongoloid dispersals Tissue Antigens 2000 55: 1–9

    Article  CAS  Google Scholar 

  25. Tokunaga K, Ohashi J, Bannai M, Juji T . Genetic link between Asians and Native Americans: evidence from HLA genes and haplotypes Hum Immunol 2001 62: 1001–1008

    Article  CAS  Google Scholar 

  26. Kimura A, Dong RD, Harada H, Sasazuki T DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA. HLA 1991, Proceedings of the 11th International Histocompatibility Workshop and Conference Oxford University Press: Oxford 1992

    Google Scholar 

  27. Goldfeld AE, Leung JY, Sawyer SA, Hartl DL . Post-genomics and the neutral theory: variation and conservation in the tumor necrosis factor-alpha promoter Gene 2000 261: 19–25

    Article  CAS  Google Scholar 

  28. Alper CA, Awdeh Z, Yunis EJ . Conserved, extended MHC haplotypes Exp Clin Immunogenet 1992 9: 58–71

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to Dan Hartl for helpful discussions and to Terrie Taylor for support of the study in Malawi, and we thank Adele Uglialoro for technical assistance and Pedro Flores-Villanueva for helpful discussions. This work was supported by grants from the American Heart Association and the NIH (GM-56492) to AEG and from the NIH(HL59838) to AEG and EJY

Author information

Author notes

  1. A D Sullivan

    Present address: Oregon Health Division, Portland, OR and Epidemiological Program Office, CDC, Atlanta, GA

  2. A Baena and J Y Leung: AB and JYL made equal contributions to this work.

Authors and Affiliations

  1. Center for Blood Research, Harvard Medical School, Boston, MA, USA

    A Baena, J Y Leung, P A Fraser, G P Uko, J C Delgado, O P Clavijo & A E Goldfeld

  2. Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA

    A D Sullivan & S R Meshnick

  3. Division of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA, USA

    I Landires & E J Yunis

  4. Hospital Antonio Lorena, Cuzco, Peru

    N Vasquez-Luna & J Quiñones-Berrocal

  5. Cambodian Health Committee, Phnom Penh, Cambodia

    S Thim

  6. Department of Community Health, University of Mangochi District Hospital, Mangochi, Malawi

    T Nyirenda

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  1. A Baena
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  7. P A Fraser
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Corresponding author

Correspondence to A E Goldfeld.

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Baena, A., Leung, J., Sullivan, A. et al. TNF-α promoter single nucleotide polymorphisms are markers of human ancestry. Genes Immun 3, 482–487 (2002). https://doi.org/10.1038/sj.gene.6363898

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