Changes in malaria parasite drug resistance in an endemic population over a 25-year period with resulting genomic evidence of selection.
J Infect Dis
; 209(7): 1126-35, 2014 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-24265439
ABSTRACT
BACKGROUND:
Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation.METHODS:
We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium falciparum drug resistance genes in 668 archived parasite-positive blood samples of a Gambian population between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin combination therapy. We separately performed genome-wide sequence analysis of 52 clinical isolates from 2008 to prospect for loci under recent directional selection.RESULTS:
Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and mdr1 genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulfadoxine resistance. Temporal changes fit a model incorporating likely selection coefficients over the period. Three of the drug resistance loci were in the top 4 regions under strong selection implicated by the genome-wide analysis.CONCLUSIONS:
Genome-wide polymorphism analysis of an endemic population sample robustly identifies loci with detailed documentation of recent selection, demonstrating power to prospectively detect emerging drug resistance genes.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Seleção Genética
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Resistência a Medicamentos
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Malária Falciparum
Tipo de estudo:
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Africa
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2014
Tipo de documento:
Article