Analysis of the genetic diversity of the Plasmodium falciparum multidrug resistance gene 5' upstream region.
Recent findings indicating a low level of polymorphism in the Plasmodium falciparum genome have led to the hypothesis that existent polymorphisms are likely to have functional significance. We tested this hypothesis by developing a map of the polymorphism in the P. falciparum multidrug resistance 1 (pfmdr1) gene 5' upstream region and assaying its correlation with drug resistance in a sample of field isolates from Dakar, Senegal. A comparison of six geographically diverse laboratory strains showed that the 1.94-kb 5'-untranslated region is highly monomorphic, with a total of four unique single nucleotide polymorphisms (SNPs) being identified. All of the mutations were localized to a 462-basepair region proximal to the transcription start point. Analysis of this region in field isolates shows the prevalence of one SNP throughout the entire population of parasites, irrespective of drug resistance status. The SNP frequency of the pfmdr1 upstream region is lower than that found in the noncoding region of other genes.
Myrick
Alissa
A
Department of Medicine, San Francisco General Hospital, University of California at San Francisco, 94110, USA.
Sarr
Ousmane
O
Dieng
Therese
T
Ndir
Omar
O
Mboup
Souleymane
S
Wirth
Dyann F
DF
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D017931:DNA Primers; D016054:DNA, Protozoan / Q000032:analysis; D019450:Genes, MDR / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D012675:Senegal / Q000453:epidemiology
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D017931:DNA Primers; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium