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Genome Biol DOI:10.1186/gb-2008-9-12-r171

Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence.

Publication TypeJournal Article
Year of Publication2008
AuthorsNeafsey, DE, Schaffner, SF, Volkman, SK, Park, D, Montgomery, P, Milner, DA, Lukens, A, Rosen, D, Daniels, R, Houde, N, Cortese, JF, Tyndall, E, Gates, C, Stange-Thomann, N, Sarr, O, Ndiaye, D, Ndir, O, Mboup, S, Ferreira, MU, Moraes, Sdo Lago, Dash, AP, Chitnis, CE, Wiegand, RC, Hartl, DL, Birren, BW, Lander, ES, Sabeti, PC, Wirth, DF
JournalGenome Biol
Date Published2008
KeywordsAnimals, Gene Frequency, Genome-Wide Association Study, Phylogeny, Plasmodium falciparum, Polymorphism, Single Nucleotide, Selection, Genetic

BACKGROUND: The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum.

RESULTS: Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, inter-population differentiation, and the degree to which allele frequencies are correlated between populations.

CONCLUSIONS: The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.


Alternate JournalGenome Biol.
PubMed ID19077304
PubMed Central IDPMC2646275
Grant ListU54 RR020278 / RR / NCRR NIH HHS / United States