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01.12.2012 | Review | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Resistance to malaria in humans: the impact of strong, recent selection

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autor:
Philip W Hedrick
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-349) contains supplementary material, which is available to authorized users.

Competing interests

The author declares there are no competing interests.

Authors’ contribution

PWH conceived and wrote this manuscript. The author read and approved the final manuscript.

Abstract

Malaria is one of the leading causes of death worldwide and has been suggested as the most potent type of selection in humans in recent millennia. As a result, genes involved in malaria resistance are excellent examples of recent, strong selection. In 1949, Haldane initially suggested that infectious disease could be a strong selective force in human populations. Evidence for the strong selective effect of malaria resistance includes the high frequency of a number of detrimental genetic diseases caused by the pleiotropic effects of these malaria resistance variants, many of which are “loss of function” mutants. Evidence that this selection is recent comes from the genetic dating of the age of a number of these malaria resistant alleles to less than 5,000 years before the present, generally much more recent than other human genetic variants. An approach to estimate selection coefficients from contemporary case–control data is presented. In the situations described here, selection is much greater than 1%, significantly higher than generally observed for other human genetic variation. With these selection coefficients, predictions are generated about the joint change of alleles S and C at the β-globin locus, and for α-thalassaemia haplotypes and S, variants that are unlinked but exhibit epistasis. Population genetics can be used to determine the amount and pattern of selection in the past and predict selection in the future for other malaria resistance variants as they are discovered.
Zusatzmaterial
Authors’ original file for figure 1
12936_2012_2496_MOESM1_ESM.pdf
Authors’ original file for figure 2
12936_2012_2496_MOESM2_ESM.pdf
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