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.

Original publication

DOI

10.1093/infdis/jit618

Type

Journal article

Journal

J Infect Dis

Publication Date

01/04/2014

Volume

209

Pages

1126 - 1135

Keywords

archival analysis, genomic surveillance, policy and practice, population genetics, resistance monitoring, Alleles, Antimalarials, DNA, Protozoan, Drug Resistance, Gambia, Genome, Protozoan, Genotype, Humans, Malaria, Falciparum, Plasmodium falciparum, Polymorphism, Single Nucleotide, Selection, Genetic, Sequence Analysis, DNA