| dc.description.abstract | Around 240 million people develop symptomatic malaria and around 1.24 million die annually from malaria globally. Over 80% of those deaths occur in sub-Saharan Africa. Symptomatic malaria in humans is initiated when merozoites, the free invasive blood-stage form, invade circulating erythrocytes. Erythrocyte invasion is facilitated by merozoite protein ligands such as erythrocyte binding ligand 1 (EBL1), merozoite surface protein 1 (MSP1) and Reticulocyte binding like homologue 4 (RH4) which bind the erythrocyte surface proteins Glycophorin B (GPB), Band 3 and Complement Receptor 1 (CR1), respectively. The merozoite proteins are also thought to be potential vaccine candidates since antibodies to these antigens have been detected in individuals exposed to malaria infection. This study aimed to analyze polymorphisms in genes coding the 3 ligands (mentioned above) receptor binding sites and compare genetic variation patterns between ligands and receptors in a population with severe malaria in Kilifi, Kenya.
The binding sites of MSP1, RH4 and EBL1 genes were amplified using conventional PCR, then sequenced by BIGDYE terminator 3.1 chemistry. Tests of neutrality and linkage disequilibrium were computed for all the 3 genes. This study identified 3 and 6 SNPs in RH4 and MSP1, respectively. EBL1 was found to be more polymorphic, with region I having 13 SNPs and region II, 8 SNPs. Of all the genes, only EBL1 like its receptor Glycophorin B (Tajima’s D of -1.81 at exon 4, p<0.05) was found to be under purifying selection, with a Tajima’s D of -1.87248 (p value<0.05) based on the receptor binding domain (region II), implying an excess of rare variants within the gene from the population studied. Receptors had similar neutrality values with their respective ligands. There was no significant selection in MSP1 and RH4 despite the mutations observed. These findings indicate that genetic variations have created different haplotypes of
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which one or two are most predominantly circulating in the studied population. Proteins like RH4 and MSP1 show hope as potential vaccine candidates due to their previously demonstrated role of inducing immune response and the conserved nature of their receptor binding domains showcased in this study | en_US |
