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SNP genotyping identifies new signatures of selection in a deep sample of West African Plasmodium falciparum malaria parasites.

Amambua-Ngwa A, Park DJ, Volkman SK, Barnes KG, Bei AK, Lukens AK, Sene P, Van Tyne D, Ndiaye D, Wirth DF, Conway DJ, Neafsey DE, Schaffner SF - Mol. Biol. Evol. (2012)

Bottom Line: We found little geographic or temporal stratification of the genetic diversity among the sampled parasites.Through application of the iHS and REHH haplotype-based tests for positive selection, we found evidence of recent selective sweeps at a known drug resistance locus, at several known antigenic loci, and at several genomic regions not previously identified as sites of recent selection.We discuss the value of deep population-specific genomic analyses for identifying selection signals within sampled endemic populations of parasites, which may correspond to local selection pressures such as distinctive therapeutic regimes or mosquito vectors.

View Article: PubMed Central - PubMed

ABSTRACT
We used a high-density single-nucleotide polymorphism array to genotype 75 Plasmodium falciparum isolates recently collected from Senegal and The Gambia to search for signals of selection in this malaria endemic region. We found little geographic or temporal stratification of the genetic diversity among the sampled parasites. Through application of the iHS and REHH haplotype-based tests for positive selection, we found evidence of recent selective sweeps at a known drug resistance locus, at several known antigenic loci, and at several genomic regions not previously identified as sites of recent selection. We discuss the value of deep population-specific genomic analyses for identifying selection signals within sampled endemic populations of parasites, which may correspond to local selection pressures such as distinctive therapeutic regimes or mosquito vectors.

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First two principal components of genotype variation. Red: Gambian samples (all directly drawn). Green: culture-adapted Senegal samples. Blue: directly drawn Senegal samples.
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mss151-F1: First two principal components of genotype variation. Red: Gambian samples (all directly drawn). Green: culture-adapted Senegal samples. Blue: directly drawn Senegal samples.

Mentions: We first checked for population structure within our sampled region. Principal components analysis (fig. 1) showed little structure, whereas FST (which measures population differentiation) indicated a small, statistically significant difference between Senegal and The Gambia (FST = 0.0072, P < 0.0001). This proved to stem from subtle differences between culture-adapted parasites (present only in the Senegal set) and parasites isolated directly from patient blood (see supplementary note and supplementary fig. S1, Supplementary Material online). We found no significant structure in time across the ∼10 years of sample collection. The lack of structure suggests enough gene flow within this region (on a scale of hundreds of kilometers) that sampling for genome-wide association studies need not be finer grained spatially, at least for this sample size. We also measured linkage disequilibrium throughout the genome and found it generally consistent with previous reports (see supplementary note and supplementary figs. S2 and S3 for details and caveats, Supplementary Material online).Fig. 1.


SNP genotyping identifies new signatures of selection in a deep sample of West African Plasmodium falciparum malaria parasites.

Amambua-Ngwa A, Park DJ, Volkman SK, Barnes KG, Bei AK, Lukens AK, Sene P, Van Tyne D, Ndiaye D, Wirth DF, Conway DJ, Neafsey DE, Schaffner SF - Mol. Biol. Evol. (2012)

First two principal components of genotype variation. Red: Gambian samples (all directly drawn). Green: culture-adapted Senegal samples. Blue: directly drawn Senegal samples.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472499&req=5

mss151-F1: First two principal components of genotype variation. Red: Gambian samples (all directly drawn). Green: culture-adapted Senegal samples. Blue: directly drawn Senegal samples.
Mentions: We first checked for population structure within our sampled region. Principal components analysis (fig. 1) showed little structure, whereas FST (which measures population differentiation) indicated a small, statistically significant difference between Senegal and The Gambia (FST = 0.0072, P < 0.0001). This proved to stem from subtle differences between culture-adapted parasites (present only in the Senegal set) and parasites isolated directly from patient blood (see supplementary note and supplementary fig. S1, Supplementary Material online). We found no significant structure in time across the ∼10 years of sample collection. The lack of structure suggests enough gene flow within this region (on a scale of hundreds of kilometers) that sampling for genome-wide association studies need not be finer grained spatially, at least for this sample size. We also measured linkage disequilibrium throughout the genome and found it generally consistent with previous reports (see supplementary note and supplementary figs. S2 and S3 for details and caveats, Supplementary Material online).Fig. 1.

Bottom Line: We found little geographic or temporal stratification of the genetic diversity among the sampled parasites.Through application of the iHS and REHH haplotype-based tests for positive selection, we found evidence of recent selective sweeps at a known drug resistance locus, at several known antigenic loci, and at several genomic regions not previously identified as sites of recent selection.We discuss the value of deep population-specific genomic analyses for identifying selection signals within sampled endemic populations of parasites, which may correspond to local selection pressures such as distinctive therapeutic regimes or mosquito vectors.

View Article: PubMed Central - PubMed

ABSTRACT
We used a high-density single-nucleotide polymorphism array to genotype 75 Plasmodium falciparum isolates recently collected from Senegal and The Gambia to search for signals of selection in this malaria endemic region. We found little geographic or temporal stratification of the genetic diversity among the sampled parasites. Through application of the iHS and REHH haplotype-based tests for positive selection, we found evidence of recent selective sweeps at a known drug resistance locus, at several known antigenic loci, and at several genomic regions not previously identified as sites of recent selection. We discuss the value of deep population-specific genomic analyses for identifying selection signals within sampled endemic populations of parasites, which may correspond to local selection pressures such as distinctive therapeutic regimes or mosquito vectors.

Show MeSH
Related in: MedlinePlus