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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Multiple genetic backgrounds of the amplified plasmodium falciparum multidrug resistance (Pfrndr1) gene and selective sweep of 184F mutation in Cambodia
Journal of Infectious Diseases, Volume 201, No. 10, Year 2010
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Description
Background. The emergence of artesunate-mefloquine (AS+MQ)-resistant Plasmodium falciparum in the Thailand-Cambodia region is a major concern for malaria control. Studies indicate that copy number increase and key alleles in the pfmdr1 gene are associated with AS+MQ resistance. In the present study, we investigated evidence for a selective sweep around pfmdr1 because of the spread of adaptive mutation and/or multiple copies of this gene in the P falciparum population in Cambodia. Methods. We characterized 13 microsatellite loci flanking (±99 kb) pfmdr1 in 93 single-clone P falciparum infections, of which 31 had multiple copies and 62 had a single copy of the pfmdr1 gene. Results. Genetic analysis revealed no difference in the mean ( ± standard deviation) expected heterozygosity (He) at loci around single (0.75 ± 0.03) and multiple (0.76 ± 0.04) copies of pfmdr1. Evidence of genetic hitchhiking with the selective sweep of certain haplotypes was seen around mutant (184F) pfmdr1 allele, irrespective of the copy number. There was an overall reduction of 28% in mean He (±SD) around mutant allele (0.56 ± 0.05), compared with wild-type allele (0.84 ± 0.02). Significant linkage disequilibrium was also observed between the loci flanking mutant pfmdr1 allele. Conclusion. The 184F mutant allele is under selection, whereas amplification of pfmdr1 gene in this population occurs on multiple genetic backgrounds. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Vinayak, Sumiti
United States, Atlanta
Centers for Disease Control and Prevention
Alam, Md Tauqeer
United States, Atlanta
Centers for Disease Control and Prevention
Sem, Rithy
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Lim, Pharath
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Muth, Sinuon
Unknown Affiliation
Maguire, Jason D.
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Rogers, William Oscar
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Fandeur, Thierry
France, Paris
Institut Pasteur, Paris
Barnwell, John W.
United States, Atlanta
Centers for Disease Control and Prevention
Escalante, Ananías A.
United States, Tempe
Arizona State University
Wongsrichanalai, Chansuda
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Ariey, Frédéric
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Meshnick, Steven Richard
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Udhayakumar, Venkatachalam
United States, Atlanta
Centers for Disease Control and Prevention
Statistics
Citations: 48
Authors: 14
Affiliations: 6
Identifiers
Doi:
10.1086/651949
ISSN:
00221899
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study