Abstract
We have studied DNA sequence variation in and around the genes ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India, with a view to investigating the relative roles of demographic history and natural selection in shaping the observed patterns of variation. The total numbers of single nucleotide polymorphisms (SNPs) detected at the ICAM1 and TNF loci were 29 and 12, respectively. Haplotype and allele frequencies differed significantly across populations. The site frequency spectra at these loci were significantly different from those expected under neutrality, and showed an excess of intermediate-frequency variants consistent with balancing selection. However, as expected under balancing selection, there was no significant reduction of F ST values compared to neutral autosomal loci. Mismatch distributions were consistent with population expansion for both loci. On the other hand, the phylogenetic network among haplotypes for the TNF locus was similar to expectations under population expansion, while that for the ICAM1 was as expected under balancing selection. Nucleotide diversity at the ICAM1 locus was an order of magnitude lower in the promoter region, compared to the introns or exons, but no such difference was noted for the TNF gene. Thus, we conclude that the pattern of nucleotide variation in these genes has been modulated by both demographic history and selection. This is not surprising in view of the known allelic associations of several polymorphisms in these genes with various diseases, both infectious and noninfectious.
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Bamshad M. and Wooding S. P. 2003 Signatures of natural selection in the human genome. Nat. Rev. Genet. 4, 99–111.
Basu A., Mukherjee N., Roy S., Sengupta S., Banerjee S., Chakraborty M. et al. 2003 Ethnic India: a genomic view, with special reference to peopling and structure. Genome Res. 13, 2277–2290.
Berendt A. R., Simmons D. L., Tansey J. C., Newbold M. and Marsh M. 1989 Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature 341, 57–59.
Bjornsdottir U. S. and Cypcar D. M. 1999 Asthma: An inflammatory mediator soup. Allergy 54, 55–61.
Dobbie M. S., Hurst R. D., Klein N. J. and Surtees R. A. 1999 Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-alpha in an in vitro model of the blood-brain barrier. Brain Res. 830, 330–336.
Fernandez-Arquero M., Arroyo R., Rubio A., Martin C., Vigil P., Conejero L. et al. 1999 Primary association of a TNF-gene polymorphism with susceptibility to multiple sclerosis. Neurology 53, 1361–1363.
Fernandez-Reyes D., Craig A. G., Kyes S. A., Peshu N., Snow R. W., Berendt A. R. et al. 1997 A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum. Mol. Genet. 6, 1357–1360.
Fu Y.-X. 1995 Statistical properties of segregating sites. Theor. Popul. Biol. 48, 172–197.
Fu Y.-X. 1997 Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics 147, 915–925.
Fu Y.-X. and Li W.-H. 1993 Statistical tests of neutrality of mutations. Genetics 133, 693–709.
Gimenez F., de Lagerie S. B., Fernandez F., Pino P. and Mazier D. 2003 Tumor necrosis factor α in the pathogenesis of cerebral malaria. Cell. Mol. Life Sci. 60, 1623–1635.
Grimsley C., Mather K. A. and Ober C. 1998 HLA-H: a pseudogene with increased variation due to balancing selection at neighboring loci. Mol. Biol. Evol. 15, 1581–1588.
Hamblin M. T. and Di Rienzo A. 2000 Detection of the signature of natural selection in humans: evidence from the Duffy blood group. Am. J. Hum. Genet. 66, 1669–1679.
Hill A. V. 1992 Malaria resistance genes: a natural selection. Trans. R. Soc. Trop. Med. Hyg. 86, 225–226.
Kawasaki A., Tsuchiya N., Hagiwara K., Takazoe M. and Tokunaga K. 2000 Independent contribution of HLS-DRB1 and TNF alpha promoter polymorphisms to the susceptibility to Crohn’s disease. Genes Immun. 1, 351–357.
Klein J., Satta Y., O’hUigin C. and Takahata N. 1993 The molecular descent of the major histocompatibility complex. Annu. Rev. Immunol. 11, 269–295.
Knight J. C. and Kwiatkowski D. 1999 Inherited variability of tumor necrosis factor production and susceptibility to infectious diseases. Proc. Assoc. Am. Physicians 111, 290–298.
Kwiatkowski D., Molyneux M. E., Stephens S., Curtis N., Klein N., Pointaire P. et al. 1993 Anti-TNF therapy inhibits fever in cerebral malaria. Q. J. Med. 86, 91–98
Majumdar P. and Majumder P. P. 1999 HAPLOPOP: A computer program package to estimate haplotype frequencies from genotype frequencies via the EM algorithm. AHGU Tech Rep 1/99, Indian Statistical Institute, Kolkata.
McGuire W., Knight J. C., Hill A. V., Allsopp C. E., Greenwood B. M. and Kwiatkowski D. 1999 Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. J. Infect. Dis. 179, 287–290.
Meager A. 1999 Cytokine regulation of cellular adhesion molecule expression in inflammation. Cytokine Growth Factor Rev. 10, 27–39.
Negoro K., Kinouchi Y., Hiwatashi N., Takahashi S., Takagi S., Satoh J. et al. 1999 Crohn’s disease is associated with novel polymorphisms in the 5′-flanking region of the tumor necrosis factor gene. Gastroenterology 117, 1062–1068.
Paloske B. L. and Howard R. J. D. 1994 Malaria, the red cell, and the endothelium. Annu. Rev. Med. 45, 283–295.
Reich D. E., Schaffner S. F., Daly M. J., McVean G., Mullikan J. C., Higgins J. M. et al. 2002 Human genome sequence variation and the influence of gene history, mutation and recombination. Nature Genet. 32, 135–142.
Rogers A. R. and Harpending H. 1992 Population growth makes waves in the distribution of pairwise genetic differences. Mol. Bio. Evol. 9, 552–569.
Rozas J., Sanchez-DelBarrio J. C., Messeguer X. and Rozas R. 2003 DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19, 2496–2497.
Sachidanandam R., Weissman D., Schmidt S. C., Kakol J. M., Stein L. D., Marth G. et al. 2001 A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409, 928–933.
Satta Y., O’hUigin C., Takahata N., and Klein J. 1994 Intensity of natural selection at the major histocompatibility complex loci. Proc. Natl. Acad. Sci. USA 91, 7184–7188.
Schneider S., Roessli D. and Excoffier L. 2000 Arlequin ver. 2.000: a software for population genetics data analysis. Genetics and Biometry Laboratory, University of Switzerland, Geneva, Switzerland.
Sengupta S., Farheen S., Mukherjee N. Dey B., Mukhopadhyay B., Sil S. K. et al. 2004 DNA Sequence variation and haplotype structure of the ICAM-1 and TNF genes in twelve ethnic groups of India reveal patterns of importance in designing association studies. Ann. Hum. Genet. 68, 574–588.
Singh K. S. 1992 People of India: an introduction. South Asia Books, New Delhi.
Striz I., Mio T., Adachi Y., Romberger D. J. and Rennard S. I. 1999 IL-4 induces ICAM-1 expression in human bronchial epithelial cells and potentiates TNF-alpha. Am. J. Physiol. 277, L58–L64.
Tajima F. 1989 Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595.
Takahata N. and Nei M. 1990 Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124, 967–978.
Takahata N., Satta Y and Klein J. 1992 Polymorphism and balancing selection at the major histocompatibility loci. Genetics 130, 925–938.
Thapar R. 2003 Early India: from the origins to AD 1300. University of California Press, Berkeley, CA.
Thio C. L., Goedert J. J., Mosbruger T., Vlahov D., Strathdee S. A., O’Brien S. J. et al. 2004 An analysis of tumor necrosis factor alpha gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection. Genes Immun. 5, 294–300.
Turner G. D., Morrison H., Jones M., Davis T. M., Looareesuwan S., Buley I. D. et al. 1994. An immunohistochemical study of the pathology of fatal malaria: evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am. J. Pathol. 145, 1057–1069.
Watterson G. A. 1975 On the number of segregating sites in genetical models without recombination. Theor. Popul. Biol. 7, 256–276.
Zeggini E., Thomson W., Kwiatkowski D., Richardson A., Ollier W. and Donn R. 2002 Linkage and association studies of single-nucleotide polymorphism-tagged tumor necrosis factor haplotypes in juvenile oligoarthritis. Arthritis Rheum. 46, 3304–3311.
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Sengupta, S., Farheen, S., Mukherjee, N. et al. Patterns of nucleotide sequence variation in ICAM1 and TNF genes in twelve ethnic groups of India: roles of demographic history and natural selection. J Genet 86, 225–239 (2007). https://doi.org/10.1007/s12041-007-0030-y
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DOI: https://doi.org/10.1007/s12041-007-0030-y