Selection and Utility of Single Nucleotide Polymorphism Markers to Reveal Fine-Scale Population Structure in Human Malaria Parasite Plasmodium falciparum

Single nucleotide polymorphisms (SNPs) have been shown to be useful in revealing population structure with continental-and regional-scale samples. In epidemiological study, a careful selection of SNPs to track disease spread in local communities would provide an important addition to traditional disease surveillance. This study used SNPs and microsatellites to examine population structure of Plasmodium falciparum at fine- scale in malaria-endemic areas of Western Kenya. A set of high performance (HP) SNPs were selected from a large SNP panel based on BELS ranking, FST values and minor allele frequency criteria. The discriminative power and assignment accuracy of different SNP panels including nonsynonymous SNPs, silent SNPs, previously published barcode SNPs, and the HP SNPs were evaluated together with microsatellites. Among all SNP panels, HP SNPs showed the highest level of differentiation and self-assignment accuracy on average among sites. Clear distinction was observed between the northern and southern P. falciparum samples, whereas samples from the south were least diverged from one another. These results were comparable to those by microsatellites. Nonsynonymous, silent, and barcode SNPs all showed similar levels of genetic variability to one another and weaker structure than the HP SNPs. We described here the procedure of selecting a set of HP SNPs from a large panel of SNPs that resolve population structure of P. falciparum between the northern and southern regions of Western Kenya. Future work is needed to determine if this procedure can result in SNPs panels capable of tracing Plasmodium spread at finer geographical scales.