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Heredity (2011) 107, 283304
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REVIEW
Population genetics of malaria resistance in humans
PW Hedrick
School of Life Sciences, Arizona State University, Tempe, AZ, USA
estimation of selection coefcients from casecontrol data and make predictions about the change for S, C and G6PD-deciency variants. In addition, I consider the predicted joint changes when the two b-globin alleles S and
C are both variable in the same population and when there is a variation for a-thalassemia and S, two unlinked, but epistatic variants. As more becomes known about genes conferring genetic resistance to malaria in humans, population genetics approaches can contribute both to investigating past selection and predicting the consequences in future generations for these variants.
Heredity (2011) 107, 283304; doi:http://dx.doi.org/10.1038/hdy.2011.16
Web End =10.1038/hdy.2011.16 ; published online 23 March 2011
Keywords: ABO; age of allele; Duffy; epistasis; G6PD; Haldane; sickle cell; thalassemia
The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria provide some of the best-known case studies of strong positive selection in modern humans. I begin by reviewing JBS Haldanes initial contribution to the potential of malaria genetic resistance in humans. Further, I discuss the population genetics aspects of many of the variants, including globin, G6PD deciency, Duffy, ovalocytosis, ABO and human leukocyte antigen variants. Many of the variants conferring resistance to malaria are loss-of-function mutants and appear to be recent polymorphisms from the last 500010 000 years or less. I discuss
Introduction
Today, the knowledge that specic genetic variants can contribute to disease resistance in humans is well known (Dronamraju, 2004; Kaslow et al., 2008). Haldane (1949a) is widely credited with rst proposing that genetic resistance to a disease was potentially an important evolutionary force in humans. Before discussing malaria resistance further, it is worthwhile to consider the initial historical contribution and insights of JBS Haldane, one of the founders of population genetics, to the population genetics of malaria resistance in humans.
Acknowledgment to the general review entitled Disease and Evolution by Haldane (1949a) is confusing because there is nothing discussed about human resistance to disease in the body of this...