Further consistent with a continental difference in the HbS mutation rate, it fits with the broader correspondence between de novo rates and observations of alleles in populations that HbS is most frequent in Africans and in some other populations in the Asian malaria belt (Flint et al. 1998) and appears de novo in our African but not in our European samples, whereas Hb-Leiden has been observed across the globe (Hardison et al. 2002; Hardison and Miller 2002) and appears de novo in both our African and European samples. Here, GSTM1 is linked to malaria.