Evolution, revolution and heresy in the genetics of infectious disease susceptibility

Adrian V S Hill, Adrian V S Hill

Abstract

Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case-control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference.

Figures

Figure 1.
Figure 1.
Association plot of the main associated locus identified in combined analysis of genome-wide association studies of tuberculosis in The Gambia and Ghana. The y-axis show the negative log of the p-value for the association test. The peak of association is in a gene-poor region, but the positions of flanking genes are shown. Adapted from Thye et al. [57].

References

    1. Allison A. C. 1954. Protection afforded by sickle-cell trait against subtertain malarial infection. Br. Med. J. 1, 290–29410.1136/bmj.1.4857.290 ()
    1. Huang Y., et al. 1996. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat. Med. 2, 1240–124310.1038/nm1196-1240 ()
    1. Arevalo-Herrera M., et al. 2005. Immunogenicity and protective efficacy of recombinant vaccine based on the receptor-binding domain of the Plasmodium vivax Duffy binding protein in Aotus monkeys. Am. J. Trop. Med. Hyg. 73, 25–31
    1. Miller L. H., Mason S. J., Clyde D. F., McGinniss M. H. 1976. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N. Engl. J. Med. 295, 302–30410.1056/NEJM197608052950602 ()
    1. Petersen K. A., Matthiesen F., Agger T., Kongerslev L., Thiel S., Cornelissen K., Axelsen M. 2006. Phase I safety, tolerability, and pharmacokinetic study of recombinant human mannan-binding lectin. J. Clin. Immunol. 26, 465–47510.1007/s10875-006-9037-z ()
    1. McClellan J., King M. C. 2010. Genetic heterogeneity in human disease. Cell 141, 210–21710.1016/j.cell.2010.03.032 ()
    1. Bousfiha A., et al. 2010. Primary immunodeficiencies of protective immunity to primary infections. Clin. Immunol. 135, 204–20910.1016/j.clim.2010.02.001 ()
    1. Gedda L., et al. 1984. Heredity and infectious diseases: a twin study. Acta Genet. Med. Gemellol (Roma) 33, 497–500
    1. Comstock G. W. 1978. Tuberculosis in twins: a re-analysis of the Prophit survey. Am. Rev. Respir. Dis. 117, 621–624
    1. Chakravarti M. R., Vogel F. 1973. A twin study on leprosy. Stuttgart, Germany: Thieme
    1. Malaty H. M., Engstrand L., Pedersen N. L., Graham D. Y. 1994. Helicobacter pylori infection: genetic and environmental influences. A study of twins. Ann. Intern. Med. 120, 982–986
    1. Lin T. M., et al. 1989. Hepatitis B virus markers in Chinese twins. Anticancer Res. 9, 737–741
    1. Newport M. J., Goetghebuer T., Weiss H. A., The MRC Gambia Twin Study Group, Whittle H., Siegrist C.-A., Marchant A. 2004. Genetic regulation of immune responses to vaccines in early life. Genes Immun. 5, 122–12910.1038/sj.gene.6364051 ()
    1. Tan P. L., Jacobson R. M., Poland G. A., Jacobsen S. J., Pankratz V. S. 2001. Twin studies of immunogenicity–determining the genetic contribution to vaccine failure. Vaccine 19, 2434–243910.1016/S0264-410X(00)00468-0 ()
    1. Fortin A., Abel L., Casanova J. L., Gros P. 2007. Host genetics of mycobacterial diseases in mice and men: forward genetic studies of BCG-osis and tuberculosis. Annu. Rev. Genomics Hum. Genet. 8, 163–19210.1146/annurev.genom.8.080706.092315 ()
    1. Tobin D. M., et al. 2010. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell 140, 717–73010.1016/j.cell.2010.02.013 ()
    1. Curtis J., et al. 2011. Association analysis of the LTA4H gene polymorphisms and pulmonary tuberculosis in 9115 subjects. Tuberculosis (Edinb.) 91, 22–2510.1016/j.tube.2010.11.001 ()
    1. Siddiqui M. R., et al. 2001. A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat. Genet. 27, 439–44110.1038/86958 ()
    1. Mira M. T., et al. 2004. Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 427, 636–64010.1038/nature02326 ()
    1. Tosh K., Meisner S., Siddiqui M. R., Balakrishnan K., Ghei S., Golding M., Sengupta U., Pitchappan R. M., Hill A. V. K. 2002. A region of chromosome 20 is linked to leprosy susceptibility in a South Indian population. J. Infect. Dis. 186, 1190–119310.1086/343806 ()
    1. Bellamy R., et al. 2000. Genetic susceptibility to tuberculosis in Africans: a genome-wide scan. Proc. Natl Acad. Sci. USA 97, 8005–800910.1073/pnas.140201897 ()
    1. Cooke G. S., et al. 2008. Mapping of a novel susceptibility locus suggests a role for MC3R and CTSZ in human tuberculosis. Am. J. Respir. Crit. Care Med. 178, 203–20710.1164/rccm.200710-1554OC ()
    1. Frodsham A. J., et al. 2006. Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proc. Natl Acad. Sci. USA 103, 9148–915310.1073/pnas.0602800103 ()
    1. Abel L., Demenais F. 1988. Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. Am. J. Hum. Genet. 42, 256–266
    1. Abel L., Cot M., Mulder L., Carnevale P., Feingold J. 1992. Segregation analysis detects a major gene controlling blood infection levels in human malaria. Am. J. Hum. Genet. 50, 1308–1317
    1. Vogel F. 1970. Controversy in human genetics. ABO blood groups and disease. Am. J. Hum. Genet. 22, 464–475
    1. Mourant A. E. 1973. Associations between hereditary blood factors and diseases. Bull. World Health Organ. 49, 93–101
    1. Hill A. V. 2006. Aspects of genetic susceptibility to human infectious diseases. Annu. Rev. Genet. 40, 469–48610.1146/annurev.genet.40.110405.090546 ()
    1. Palmer M. S., Dryden A. J., Hughes J. T., Collinge J. 1991. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt–Jakob disease. Nature 352, 340–34210.1038/352340a0 ()
    1. Genton B., AI-Yaman F., Mgone C. S., Alexander N., Paniu M. M., Alpers M. P., Mokela D. 1995. Ovalocytosis and cerebral malaria. Nature 378, 564–56510.1038/378564a0 ()
    1. Lindesmith L., Moe C., Marionneau S., Ruvoen N., Jiang X., Lindblad L., Stewart P., LePendu J., Baric R. 2003. Human susceptibility and resistance to Norwalk virus infection. Nat. Med. 9, 548–55310.1038/nm860 ()
    1. Zhang F. R., et al. 2009. Genomewide association study of leprosy. N. Engl. J. Med. 361, 2609–261810.1056/NEJMoa0903753 ()
    1. Pereyra F., et al. 2010. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330, 1551–155710.1126/science.1195271 ()
    1. Mbarek H., et al. 2011. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum. Mol. Genet. 20, 3884–389210.1093/hmg/ddr301 ()
    1. Fry A. E., et al. 2008. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria. Hum. Mol. Genet. 17, 567–57610.1093/hmg/ddm331 ()
    1. Ruwende C., et al. 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376, 246–24910.1038/376246a0 ()
    1. Davila S., et al. 2010. Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease. Nat. Genet. 42, 772–77610.1038/ng.640 ()
    1. Khor C. C., et al. 2007. A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat. Genet. 39, 523–52810.1038/ng1976 ()
    1. Wong S. H., et al. 2010. Leprosy and the adaptation of human toll-like receptor 1. PLoS Pathog. 6, e1000979.10.1371/journal.ppat.1000979 ()
    1. Thomas D. L., et al. 2009. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461, U752–U79810.1038/nature08463 ()
    1. Roy S., et al. 2002. MBL genotype and risk of invasive pneumococcal disease: a case–control study. Lancet 359, 1569–157310.1016/S0140-6736(02)08516-1 ()
    1. Vannberg F. O., Chapman S. J., Hill A. V. 2011. Human genetic susceptibility to intracellular pathogens. Immunol. Rev. 240, 105–11610.1111/j.1600-065X.2010.00996.x ()
    1. Kaslow R. A., McNicholl J., Hill A. V. S. 2008. Genetic susceptibility to infectious diseases. Oxford, UK: Oxford University Press
    1. O'Neill L. A., Bowie A. G. 2010. Sensing and signaling in antiviral innate immunity. Curr. Biol. 20, R328–R33310.1016/j.cub.2010.01.044 ()
    1. Khor C. C., et al. 2010. CISH and susceptibility to infectious diseases. N. Engl. J. Med. 362, 2092–210110.1056/nejmoa0905606 ()
    1. Johnson C. M., et al. 2007. A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J. Immunol. 178, 7520–7524
    1. Ma X., Liu Y., Gowen B. B., Graviss E. A., Clark A. G., Musser J. M. 2007. Full-exon resequencing reveals toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS ONE 2, e1318.10.1371/journal.pone.0001318 ()
    1. Lee Y. H., Rho Y. H., Choi S. J., Ji J. D., Song G. G., Nath S. K., Harley J. B. 2006. The PTPN22 C1858T functional polymorphism and autoimmune diseases: a meta-analysis. Rheumatology (Oxford) 46, 49–5610.1093/rheumatology/kel170 ()
    1. Chapman S. J., et al. 2006. PTPN22 and invasive bacterial disease. Nat. Genet. 38, 499–50010.1038/ng0506-499 ()
    1. Rani R., Singh A., Israni N., Sharma P., Kar H. K. 2009. The role of polymorphic protein tyrosine phosphatase non-receptor type 22 in leprosy. J. Invest. Dermatol. 129, 2726–272810.1038/jid.2009.140 ()
    1. Chapman S. J., et al. 2007. IkappaB genetic polymorphisms and invasive pneumococcal disease. Am. J. Respir. Crit. Care Med. 176, 181–18710.1164/rccm.200702-169OC ()
    1. Chapman S. J., et al. 2010. NFKBIZ polymorphisms and susceptibility to pneumococcal disease in European and African populations. Genes Immun. 11, 319–32510.1038/gene.2009.76 ()
    1. Chapman S. J., et al. 2010. Common NFKBIL2 polymorphisms and susceptibility to pneumococcal disease: a genetic association study. Crit. Care 14, R227.10.1186/cc9377 ()
    1. Liu L., et al. 2011. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J. Exp. Med. 208, 1635–164810.1084/jem.20110958 ()
    1. Wellcome Trust Case–Control Consortium 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–67810.1038/nature05911 ()
    1. Manolio T. A., et al. 2009. Finding the missing heritability of complex diseases. Nature 461, 747–75310.1038/nature08494 ()
    1. Thye T., et al. 2010. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nat. Genet. 42, 739–74110.1038/ng.639 ()
    1. Jallow M., et al. 2009. Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat. Genet. 41, 657–66510.1038/ng.388 ()
    1. Troyer J. L., et al. 2011. Genome-wide association study implicates PARD3B-based AIDS restriction. J. Infect. Dis. 203, 1491–150210.1093/infdis/jir046 ()
    1. Thye T., et al. In press. Common variants at 11p13 are associated with susceptibility to tuberculosis. Nat. Genet.
    1. Wong S. H., Hill A. V., Vannberg F. O. 2010. Genomewide association study of leprosy. N. Engl. J. Med. 362, 1446–1447; author reply 1447–144810.1056/nejmc1001451 ()
    1. Behr M. A., Schurr E. 2006. Mycobacteria in Crohn's disease: a persistent hypothesis. Inflamm. Bowel Dis. 12, 1000–100410.1097/01.mib.0000228183.70197.dd ()
    1. Fellay J., Shianna K. V., Telenti A., Goldstein D. B. 2010. Host genetics and HIV-1: the final phase? PLoS Pathog. 6, e1001033.10.1371/journal.ppat.1001033 ()
    1. Fellay J., et al. 2009. Common genetic variation and the control of HIV-1 in humans. PLoS Genet. 5, e1000791.10.1371/journal.pgen.1000791 ()
    1. Malaria Genomic Epidemiology Network 2008. A global network for investigating the genomic epidemiology of malaria. Nature 456, 732–73710.1038/nature07632 ()
    1. Gorlov I. P., Gorlova O. Y., Frazier M. L., Spitz M. R., Amos C. I. 2011. Evolutionary evidence of the effect of rare variants on disease etiology. Clin. Genet. 79, 199–20610.1111/j.1399-0004.2010.01535.x ()
    1. Casanova J. L., Abel L. 2007. Primary immunodeficiencies: a field in its infancy. Science 317, 617–61910.1126/science.1142963 ()
    1. Alcais A., Quintana-Murci L., Thaler D. S., Schurr E., Abel L., Casanova J.-L. 2010. Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity? Ann. NY Acad. Sci. 1214, 18–3310.1111/j.1749-6632.2010.05834.x ()
    1. Casanova J. L., Abel L. 2005. Inborn errors of immunity to infection: the rule rather than the exception. J. Exp. Med. 202, 197–20110.1084/jem.20050854 ()
    1. Choi M., et al. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc. Natl Acad. Sci. USA 106, 19 096–19 10110.1073/pnas.0910672106 ()
    1. Kim D. W., Nam S. H., Kim R. N., Choi S. H., Park H. S. 2010. Whole human exome capture for high-throughput sequencing. Genome 53, 568–57410.1139/G10-025 ()
    1. Teer J. K., Mullikin J. C. 2010. Exome sequencing: the sweet spot before whole genomes. Hum. Mol. Genet. 19, R145–15110.1093/hmg/ddq333 ()
    1. Smirnova I., Mann N., Dols A., Derkx H. H., Hibberd M. L., Levin M., Beutler B. 2003. Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility. Proc. Natl Acad. Sci. USA 100, 6075–608010.1073/pnas.1031605100 ()
    1. Grossman S. R., et al. 2010. A composite of multiple signals distinguishes causal variants in regions of positive selection. Science 327, 883–88610.1126/science.1183863 ()
    1. Fincham J. R. 1972. Heterozygous advantage as a likely general basis for enzyme polymorphisms. Heredity 28, 387–39110.1038/hdy.1972.49 ()
    1. Hedrick P. W. 1972. Maintenance of genetic variation with a frequency-dependent selection model as compared to the overdominant model. Genetics 72, 771–775
    1. Bodmer W. F. 1975. Evolution of HL-A and other major histocompatibility systems. Genetics 79(Suppl.), 293–304
    1. Hill A. V. S. 1991. HLA associations with malaria in Africa: some implications for MHC evolution. In Molecular evolution of the major histocompatibility complex (eds Klein J., Klein D.), pp. 403–420 Berlin, Germany: Springer
    1. Sabeti P. C., et al. 2007. Genome-wide detection and characterization of positive selection in human populations. Nature 449, 913–91810.1038/nature06250 ()
    1. Sanchez-Mazas A., et al. 2011. Immunogenetics as a tool in anthropological studies. Immunology 133, 143–16410.1111/j.1365-2567.2011.03438.x ()
    1. Hill A. V. S., et al. 1985. Melanesians and Polynesians share a unique alpha-thalassemia mutation. Am. J. Hum. Genet. 37, 571–80
    1. de Vries R. R., Fat R. F., Nijenhuis L. E., van Rood J. J. 1976. HLA-linked genetic control of host response to Mycobacterium leprae. Lancet 2, 1328–133010.1016/S0140-6736(76)91975-9 ()
    1. Monot M., et al. 2009. Comparative genomic and phylogeographic analysis of Mycobacterium leprae. Nat. Genet. 41, 1282–128910.1038/ng.477 ()
    1. Caws M., et al. 2008. The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog. 4, e1000034.10.1371/journal.ppat.1000034 ()

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel