Population genetics of malaria resistance in humans

G6PD deficiency and malaria selection

“…Specifically, he quotes data from a study (Ruwende et al, 1995) conducted in Gambia and in Kenya, from which it was claimed that the degree of protection was similar in hemizygous G6PD-deficient males and in heterozygous G6PD-deficienct females. Hedrick (2011) points out that this is rather paradoxical, because it would lead to fixation of the G6PD-deficient allele(s), which does not seem to have taken place; and he reproduces from that paper a figure that offers an explanation on the basis of an ad-hoc hypothesis.…”

“…In his valuable review on genetics of malaria resistance, Hedrick (2011) tackles the interesting issue of the protection against Plasmodium falciparum afforded by G6PD deficiency. Specifically, he quotes data from a study (Ruwende et al, 1995) conducted in Gambia and in Kenya, from which it was claimed that the degree of protection was similar in hemizygous G6PD-deficient males and in heterozygous G6PD-deficienct females.…”

Selection and Mutation for α Thalassemia in Nonmalarial and Malarial Environments

“…From selection estimates using these data, it is predicted that the observed frequencies in the Kenya and Papua New Guinea populations would be predicted after approximately 2975 and 5850 years of selection in malarial environments, given that the initial frequencies are those observed in nonmalarial environments. This time interval is generally similar to the age of malarial protective variants at other genes, such as the β globin structural alleles S (sickle cell), C, and E and G6PD deficiency (Hedrick, 2011a). Further, this time frame is not inconsistent with the known archeological record in eastern Melanesia that goes back to around 4000 years ago (Flint et al, 1998).…”

“…There is extensive support for the general importance of selection for resistance to malaria for hemoglobinopathies in general (for a recent review, see Hedrick, 2011a) and for α thalassemia in particular. However, for population genetics prediction it is necessary to obtain a numerical estimate of the extent of selection for different genotypes.…”

“…A major exception to this pattern are the human hemoglobinopathies, primarily the thalassemias, where there is a deficient synthesis of α or β globin protein molecules, and the structural mutants at the β globin gene, S (sickle cell), C, and E (Flint et al, 1998;Hedrick, 2011a). In fact, α + thalassemia appears to be the commonest monogenic disease in the world with a frequency over 80% in some populations, such as in Nepal, parts of India, and Papua New Guinea (Flint et al, 1998).…”