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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.

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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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Signals of selective sweeps. Significance −log10(P-value) for all SNPs for (a) REHH and (b) iHS; QQ plots (observed vs. expected P values) for (c) REHH and (d) iHS. Panels c and d also show the P value distribution with sweep loci removed (teal). Dashed lines: Bonferroni significance (0.05 level).
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mss151-F2: Signals of selective sweeps. Significance −log10(P-value) for all SNPs for (a) REHH and (b) iHS; QQ plots (observed vs. expected P values) for (c) REHH and (d) iHS. Panels c and d also show the P value distribution with sweep loci removed (teal). Dashed lines: Bonferroni significance (0.05 level).

Mentions: We identified possible selective sweeps using two haplotype-based tests for positive selection: relative extended haplotype homozygosity (REHH) (Sabeti et al. 2002) and integrated haplotype score (iHS) (Voight et al. 2006). These tests identify alleles that lie on unusually long haplotypes for that region, indicative of a recent selective sweep. We detected 11 loci with genome-wide significance, including the well-characterized pfcrt locus (Fidock et al. 2000) and a large region on chromosome 6 (fig. 2, table 1; supplementary table S2 has detailed annotation, Supplementary Material online). Five of the loci overlap with previously reported signals (Mu et al. 2010; Van Tyne et al. 2011). The signals of selection appeared consistently in both our directly drawn and our culture-adapted parasite sets (supplementary fig. S4, Supplementary Material online) and were little changed when we restricted our analysis to a 2-year time period (supplementary fig. S5, Supplementary Material online) or used a uniform recombination map. After removing the 11 loci, the remainder of the genome roughly conforms to the expectation for test scores (fig. 2c and d).Fig. 2.


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)

Signals of selective sweeps. Significance −log10(P-value) for all SNPs for (a) REHH and (b) iHS; QQ plots (observed vs. expected P values) for (c) REHH and (d) iHS. Panels c and d also show the P value distribution with sweep loci removed (teal). Dashed lines: Bonferroni significance (0.05 level).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

mss151-F2: Signals of selective sweeps. Significance −log10(P-value) for all SNPs for (a) REHH and (b) iHS; QQ plots (observed vs. expected P values) for (c) REHH and (d) iHS. Panels c and d also show the P value distribution with sweep loci removed (teal). Dashed lines: Bonferroni significance (0.05 level).
Mentions: We identified possible selective sweeps using two haplotype-based tests for positive selection: relative extended haplotype homozygosity (REHH) (Sabeti et al. 2002) and integrated haplotype score (iHS) (Voight et al. 2006). These tests identify alleles that lie on unusually long haplotypes for that region, indicative of a recent selective sweep. We detected 11 loci with genome-wide significance, including the well-characterized pfcrt locus (Fidock et al. 2000) and a large region on chromosome 6 (fig. 2, table 1; supplementary table S2 has detailed annotation, Supplementary Material online). Five of the loci overlap with previously reported signals (Mu et al. 2010; Van Tyne et al. 2011). The signals of selection appeared consistently in both our directly drawn and our culture-adapted parasite sets (supplementary fig. S4, Supplementary Material online) and were little changed when we restricted our analysis to a 2-year time period (supplementary fig. S5, Supplementary Material online) or used a uniform recombination map. After removing the 11 loci, the remainder of the genome roughly conforms to the expectation for test scores (fig. 2c and d).Fig. 2.

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