Selection and Common Monogenic Disease


Major environmental changes following the development of agriculture have had a profound effect on the human gene pool by means of adaptive responses to new ecological relationships. The frequent occurrence of serious inherited red cell diseases in many parts of the world as a direct result of chronic exposure to malaria is an example that probably has many parallels with other genetic and infectious diseases.

Keywords: haemoglobin; thalassaemia; malaria; infectious disease

Figure 1.

Geographical distribution of some of the more common β thalassaemia mutations. Regions where malaria is or was prevalent are shaded pink. IVS, intervening sequence, or intron.



Allen SJ, O'Donnell A, Alexander NDE et al. (1997) α Thalassaemia protects children from disease caused by other infections as well as malaria. Proceedings of the National Academy of Sciences of the USA 94: 14736–14741.

Flint J, Hill AVS, Bowden DK et al. (1986) High frequencies of α‐thalassaemia are the result of natural selection by malaria. Nature 321: 744–749.

Garrod AE (1931) The Inborn Factors in Disease. Reprinted in facsimile with annotations in Scriver CS and Childs B (1989) Garrod's Inborn Factors in Disease. Oxford: Oxford University Press.

Haldane JBS (1949) The rate of mutation of human genes. Proceedings of the 8th International Congress of Genetics. Hereditas (supplement 35): 267–273.

Hill AVS, Allsop CEM and Kwiatkowski D et al. (1991) Common west African HLA antigens are associated with protection from severe malaria. Nature 352: 595–600.

McGuire W, Hill AVS, Allsopp CEM, Greenwood BM and Kwiatkowski D (1994) Variation in the TNF‐α promoter region associated with susceptibility to cerebral malaria. Nature 371: 508–511.

Miller LH (1994) Impact of malaria on genetic polymorphism and genetic diseases in Africans and African Americans. Proceedings of the National Academy of Sciences of the USA 91: 2415–2419.

Thompson EA and Neel JV (1997) Allelic disequilibrium and allele frequency distribution as a function of social and demographic history. American Journal of Human Genetics 60: 197–204.

Williams TN, Maitland K, Bennett S et al. (1996) High incidence of malaria in α‐thalassaemic children. Nature 383: 522–525.

Further Reading

Flint J, Harding RM, Boyce AJ and Clegg JB (1998) Population genetics of the haemoglobinopathies. In: Baillière's Clinical Haematology Vol. 11, pp. 1–51.

McLeod RE, Buschman E, Arbuckle LD and Skamene E (1995) Immunogenetics in the analysis of resistance to intracellular pathogens. Current Opinion in Immunology 7: 539–552.

Nesse RM and Williams GC (1998) Evolution and the origins of disease. Scientific American (November): 58–65.

Weatherall DJ and Clegg JB (1981) The Thalassaemia Syndromes. Oxford: Blackwell Scientific Publications.

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Clegg, John(Apr 2001) Selection and Common Monogenic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0002294]