Genome-Wide SNP Genotyping Highlights the Role of Natural Selection in Plasmodium Falciparum Population Divergence

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Genome-Wide SNP Genotyping Highlights the Role of Natural Selection in Plasmodium Falciparum Population Divergence

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Title: Genome-Wide SNP Genotyping Highlights the Role of Natural Selection in Plasmodium Falciparum Population Divergence
Author: Wirth, Dyann F.; Sabeti, Pardis C.; Lander, Eric S.; Birren, Bruce W.; Hartl, Daniel; Wiegand, Roger; Chitnis, Chetan E.; Dash, Aditya P.; do Lago Moraes, Sandra; Ferreira, Marcelo U.; Mboup, Soulyemane; Ndir, Omar; Ndiaye, Daouda; Ousmane, Sarr; Stange-Thomann, Nicole; Gates, Casey; Tyndall, Erin; Cortese, Joseph F.; Houde, Nathan; Daniels, Rachel; Rosen, David; Lukens, Amanda; Milner, Danny; Montgomery, Philip; Park, Daniel; Volkman, Sarah K.; Schaffner, Stephen F.; Neafsey, Daniel

Note: Order does not necessarily reflect citation order of authors.

Citation: Neafsey, Daniel E., Stephen F. Schaffner, Sarah K. Volkman, Daniel Park, Philip Montgomery, Danny A. Milner Jr., Amanda Lukens, et al. 2008. Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence. Genome Biology 9(12): R171.1-R171.16.
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Abstract: 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.
Published Version: http://dx.doi.org/10.1186/gb-2008-9-12-r171
Other Sources: http://genomebiology.com/2008/9/12/R171
Terms of Use: This article is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#OAP
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:3425892

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  • FAS Scholarly Articles [7103]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University
 
 

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