Abstract
Recent studies have shown that the relatively short period of exposure of human populations to malaria has left in its wake a wide range of genetic diversity. And there is growing evidence that other infectious agents have, or are, having the same effect. By integrating further studies of human populations with genetic analyses of susceptibility to murine malaria it should now be possible to determine some of the mechanisms involved in the variation of susceptibility to infectious disease, information which may have important practical implications for both the diagnosis and better management of these conditions.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cooke GS, Hill AVS . Genetics of susceptibility to human infectious disease Nat Rev Genet 2001 2: 967–977
Haldane JBS . The rate of mutation of human genes Proc VIII Int Cong Genetics Hereditas 1949 35: 267–273
Lederberg J . J.B.S. Haldane (1949) on infectious disease and evolution Genetics 1999 153: 1–3
Weatherall DJ, Clegg JB . The Thalassaemia Syndromes. 4th edn Blackwell Science: Oxford 2001
Huisman THJ, Carver MFH, Efremov GD . A Syllabus of Human Hemoglobin Variants Sickle Cell Foundation: Augusta, GA 1998
Livingstone FB . Frequencies of Hemoglobin Variants Oxford University Press: New York, Oxford 1985
Weatherall DJ, Clegg JB . Inherited haemoglobin disorders: an increasing global health problem Bull WHO 2001 79: 704–712
Antonarakis SE, Boehm CD, Giardina PVJ, Kazazian HH . Non random association of polymorphic restriction sites in theb-globin gene complex Proc Natl Acad Sci USA 1982 79: 137–141
Orkin SH, Kazazian HH Jr, Antonarakis SE et al. Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster Nature 1982 296: 627–631
Higgs DR, Wainscoat JS, Flint J et al. Analysis of the human α-globin gene cluster reveals a highly informative genetic locus Proc Natl Acad Sci USA 1986 83: 5165–5169
Flint J, Harding RM, Boyce AJ, Clegg JB . The population genetics of the haemoglobinopathies In: Higgs DR, Weatherall DJ (eds) Baillière’s Clinical Haematology; ‘Haemoglobinopathies’ Baillière Tindall and W.B. Saunders: London 1998 pp 1–51
Huisman THJ, Carver MFH, Baysal E . A Syllabus of Thalassemia Mutations The Sickle Cell Anemia Foundation: Augusta 1997
Allison AC . Population genetics of abnormal haemoglobins and glucose-6-phosphate dehydrogenase deficiency In: Jonxis JHP (ed) Abnormal Haemoglobins in Africa Blackwell Scientific Publications: Oxford 1965 p 365
Hill AV, Allsopp CEM, Kwiatkowski D et al. Common West African HLA antigens are associated with protection from severe malaria Nature 1991 352: 595–600
Modiano D, Luoni G, Sirima BS et al. Haemoglobin C protects against clinical Plasmodium falciparum malaria Nature 2001 414: 305–308
Flint J, Hill AVS, Bowden DK et al. High frequencies of α thalassaemia are the result of natural selection by malaria Nature 1986 321: 744–749
O’Shaughnessy DF, Hill AVS, Bowden DK, Weatherall DJ, Clegg JB with collaborators. Globin genes in Micronesia: origins and affinities of Pacific Island peoples Am J Hum Genet 1990 46: 144–155
Allen SJ, O’Donnell A, Alexander NDE et al. α+-thalassaemia protects children against disease due to malaria and other infections Proc Natl Acad Sci USA 1997 94: 14736–14741
Chakravarti A, Buetow KH, Antonarakis SE, Waber PG, Boehm CD, Kazazian HH . Nonuniform recombination within the human β-globin gene cluster Am J Hum Genet 1984 36: 1239–1258
Flint J, Harding RM, Clegg JB, Boyce AJ . Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants Hum Genet 1993 91: 91–117
Fullerton SM, Harding RM, Boyce AJ, Clegg JB . Molecular and population genetic analysis of allelic sequence diversity at the human β globin locus Proc Natl Acad Sci USA 1994 91: 1805–1809
Luzzi GA, Merry AH, Newbold CI, Marsh K, Pasvol G, Weatherall DJ . Surface antigen expression on Plasmodium falciparum-infected erythrocytes is modified in α- and β-thalassemia J Exp Med 1991 173: 785–791
Pasvol G, Weatherall DJ, Wilson RJ . Effects of foetal haemoglobin on susceptibility of red cells to Plasmodium falciparum Nature 1977 270: 171–173
Williams TN, Maitland K, Bennett S et al. High incidence of malaria in α-thalassaemic children Nature 1996 383: 522–525
Rees DC, Williams TN, Maitland K, Clegg JB, Weatherall DJ . Alpha thalassemia is associated with increased soluble transferrin receptor levels Brit J Haemat 1998 103: 365–370
Carlson J, Nash GB, Gabutti V, Al-Yaman F, Wahlgren M . Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation Blood 1994 84: 3909–3914
Tournamille C, Colin Y, Cartron JP, Le Van Kim C . Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals Nat Genet 1995 10: 224–228
Miller LH, Mason SJ, Clyde DF, McGinniss MH . The resistance factor to Plasmodium vivax in Blacks N Engl J Med 1976 295: 302–304
Weatherall DJ . Host genetics and infectious disease Parasitol 1996 112: S23–S29
Luzzatto L, Mehta A, Vulliamy T . Glucose 6-phosphate dehydrogenase In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B (eds) The Metabolic and Molecular Basis of Inherited Disease. 8th edn McGraw Hill: New York 2001 pp 4517–4554
Ruwende C, Khoo SC, Snow RW et al. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria Nature 1995 376: 246–249
Ganczakowski M, Town M, Bowden DK et al. Multiple glucose 6-phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (Southwestern Pacific) Am J Hum Genet 1995 56: 294–301
Mgone CS, Koki G, Paniu MM et al. Occurrence of the erythrocyte band 3 (AE1) gene deletion in relation to malaria endemicity in Papua New Guinea Trans Roy Soc Trop Med Hyg 1996 90: 228–231
Genton B, Al-Yaman F, Mgone CS, Alexander N, Paniu MM, Alpers MP . Ovalocytosis and cerebral malaria Nature 1995 378: 564–565
Allen SJ, O’Donnell A, Alexander NDE et al. Prevention ofcerebral malaria in children in Papua New Guinea by Southeast Asian ovalocytosis band 3 Am J Trop Med Hyg 1999 60: 1056–1060
Hill AVS, Elvin J, Willis A et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria Nature 1992 360: 434–439
McGuire W, Hill AVS, Allsopp CEM, Greenwood BM, Kwiatkowski D . Variation in the TNF-α promoter region is associated with susceptibility to cerebral malaria Nature 1994 371: 508–511
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW . Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation Proc Natl Acad Sci USA 1997 94: 3195–3199
Knight JC, Udalova J, Hill AV et al. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria Nat Genet 1999 22: 145–150
Aitman TJ, Cooper LD, Norsworthy PJ et al. Malaria susceptibility and CD36 mutation Nature 2000 405: 1015–1016
Pain A, Urban BC, Kai O et al. A non-sense mutation in Cd36 gene is associated with protection from severe malaria Lancet 2001 357: 1502–1503
Fernandez-Reyes D, Craig AG, Kyes SA et al. A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya Hum Mol Genet 1997 6: 1357–1360
Bellamy R, Kwiatkowski D, Hill AV . Absence of an association between intercellular adhesion molecule 1, complement receptor 1 and interleukin 1 receptor antagonist gene polymorphisms and severe malaria in a West African population Trans Roy Soc Trop Med Hyg 1998 92: 312–316
Modiano D, Petrarca V, Sirima BS et al. Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups Proc Natl Acad Sci USA 1996 93: 13206–13211
Fortin A, Belouchi A, Tam MF et al. Genetic control of blood parasitaemia in mouse malaria maps to chromosome 8 Nat Genet 1997 17: 382–383
Foote SJ, Burt RA, Baldwin SM et al. Mouse loci for malaria-induced mortality and the control of parasitaemia Nat Genet 1997 17: 380–381
Fortin A, Cardon LR, Tam M, Skamene E, Stevenson MM, Gros P . Identification of a malaria new susceptibility locus (Char4) in recombinant congenic strains of mice Proc Natl Acad Sci USA 2001 98: 10793–10798
Currat M, Trabuchet G, Rees D et al. Molecular analysis of the β-globin gene cluster in the Niokholo Mandenka population reveals a recent origin of the βS Senegal mutation Am J Hum Genet 2002 70: 207–223
Tishkoff SA, Varkonyi R, Cahinhinan N et al. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance Science 2001 293: 455–462
Volkman SK, Barry AE, Lyons EJ et al. Recent origin of Plasmodium falciparum from a single progenitor Science 2001 293: 482–484
Rich SM, Ayala FJ . Population structure and recent evolution of Plasmodium falciparum Proc Natl Acad Sci USA 2000 97: 6994–7001
Weatherall DJ, Clegg JB, Kwiatkowski D . The role of genomics in studying genetic susceptibility to infectious disease Genome Res 1997 7: 967–973
Roy S . Association of vitamin D receptor genotype with leprosy type J Infect Dis 1999 179: 187–191
Bellamy R, Ruwende C, Corrah T et al. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene J Infect Dis 1999 179: 721–724
Dean M, Carrington M, Winkler C et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study Science 1996 273: 1856–1862
Kostrikis LG, Neumann AU, Thomson B et al. A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants J Virol 1999 73: 10264–10271
Martin MP, Dean M, Smith MW et al. Genetic acceleration of AIDS progression by a promoter variant of CCR5 Science 1998 282: 1907–1911
Smith MW, Dean M, Carrington M et al. Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study Science 1997 277: 959–965
Winkler C, Modi W, Smith MW et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) Science 1998 279: 389–393
Marquet S, Abel L, Hillaire D, Dessein A . Full results of the genome-wide scan which localises a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33 Eur J Hum Genet 1999 7: 88–97
Acknowledgements
We thank Liz Rose for typing this manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors’ work was supported by the Medical Research Council and The Wellcome Trust.
Rights and permissions
About this article
Cite this article
Weatherall, D., Clegg, J. Genetic variability in response to infection: malaria and after. Genes Immun 3, 331–337 (2002). https://doi.org/10.1038/sj.gene.6363878
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363878
Keywords
This article is cited by
-
Periodontal Infectogenomics
Inflammation and Regeneration (2018)
-
FOXO3A regulatory polymorphism and susceptibility to severe malaria in Gabonese children
Immunogenetics (2015)
-
Genetic evidence of regulatory gene variants of the STAT6, IL10R and FOXP3 locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children
Malaria Journal (2013)
-
Genetic polymorphisms linked to susceptibility to malaria
Malaria Journal (2011)
-
Genetic analysis in mice identifies cysteamine as a novel partner for artemisinin in the treatment of malaria
Mammalian Genome (2011)