Extended Data Fig. 9: Differences in parasite development between genotypes.

a–d, Representative photomicrographs of blood smears of parasite cultures measured in RBCs from individuals bearing the alleles indicated at the top of the corresponding panels (top: large field, bottom: zoom) at different time points throughout the assay: 24, 48, 72, 96, 120 and 144 hpi homozygotes for the IoE allele rs9349205-A, for the WT allele rs112233623-C, and WT for G6PD-Med (IoE/IoE|WT/WT;G6PD-WT) (a); homozygotes for the WT alleles rs9349205-G, rs112233623-C and WT for G6PD (WT/WT|WT/WT;G6PD-WT) (b); homozygotes for the derived IoE allele rs9349205-A, for the derived DoE allele rs112233623-T and WT for G6PD (IoE/IoE|DoE/DoE;G6PD-WT) (c); and homozygotes for the WT alleles rs9349205-G, rs112233623-C, and hemizygous for the G6PD Mediterranean deficiency allele (WT/WT|WT/WT; G6PD-Med) (d) (n = 14, 7, 17 and 5 biological independent samples derived from selected donors, respectively). The scale bars are 10 μm. In a,b, the photomicrographs show a similar pattern, with Plasmodium cultures remaining synchronous up to 144 h post-invasion. By contrast, in c, the photomicrographs show that parasite growth is significantly slowed in the CCND3 IoE/IoE|DoE/DoE genotype, similar to the impaired development observed in G6PD-Med deficient individuals (d). This phenomenon is evident by a decrease in parasitaemia, becoming more pronounced from 72 h onwards, by an increase in the number of dead parasites, and by an abundance of pycnotic nuclei of P. falciparum (c,d), compared to IoE/IoE |WT/WT;G6PD-WT (a) and WT/WT|WT/WT G6PD-WT control group (b).