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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Discordant patterns of genetic variation at two chloroquine resistance loci in worldwide populations of the malaria parasite Plasmodium falciparum
Antimicrobial Agents and Chemotherapy, Volume 52, No. 6, Year 2008
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Description
Mutations in the chloroquine resistance (CQR) transporter gene of Plasmodium falciparum (Pfcrt; chromosome 7) play a key role in CQR, while mutations in the multidrug resistance gene (Pfmdr1; chromosome 5) play a significant role in the parasite's resistance to a variety of antimalarials and also modulate CQR. To compare patterns of genetic variation at Pfcrt and Pfmdr1 loci, we investigated 460 blood samples from P. falciparum-infected patients from four Asian, three African, and three South American countries, analyzing microsatellite (MS) loci flanking Pfcrt (five loci [∼40 kb]) and Pfmdr1 (either two loci [∼5 kb] or four loci [∼10 kb]). CQR Pfmdr1 allele-associated MS haplotypes showed considerably higher genetic diversity and higher levels of subdivision than CQR Pfcrt allele-associated MS haplotypes in both Asian and African parasite populations. However, both Pfcrt and Pfmdr1 MS haplotypes showed similar levels of low diversity in South American parasite populations. Median-joining network analyses showed that the Pfcrt MS haplotypes correlated well with geography and CQR Pfcrt alleles, whereas there was no distinct Pfmdr1 MS haplotype that correlated with geography and/or CQR Pfmdr1 alleles. Furthermore, multiple independent origins of CQR Pfmdr1 alleles in Asia and Africa were inferred. These results suggest that variation at Pfcrt and Pfmdr1 loci in both Asian and African parasite populations is generated and/or maintained via substantially different mechanisms. Since Pfmdr1 mutations may be associated with resistance to artemisinin combination therapies that are replacing CQ, particularly in Africa, it is important to determine if, and how, the genetic characteristics of this locus change over time. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2415780/bin/supp_52_6_2212__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2415780/bin/supp_52_6_2212__1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2415780/bin/supp_52_6_2212__2.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2415780/bin/supp_52_6_2212__3.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2415780/bin/supp_52_6_2212__4.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2415780/bin/supp_52_6_2212__5.pdf
Authors & Co-Authors
Mehlotra, Rajeev K.
United States, Cleveland
Case School of Medicine
United States, Cleveland
Case Western Reserve University
Mattera, Gabriel
United States, Cleveland
Case School of Medicine
Bockarie, Moses John
Papua new Guinea, Goroka
Papua new Guinea Institute of Medical Research
Maguire, Jason D.
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Baird, John Kevin
Indonesia, Jakarta
U.s. Naval Medical Research Unit No. 2, Jakarta
Sharma, Yagya Dutta
India, New Delhi
All India Institute of Medical Sciences, new Delhi
Alifrangis, Michael
Denmark, Copenhagen
Københavns Universitet
Dorsey, Grant M.
United States, San Francisco
Ucsf School of Medicine
Rosenthal, Philip Jon
United States, San Francisco
Ucsf School of Medicine
Fryauff, David J.
Egypt, Cairo
U.s. Naval Medical Research Unit No. 3, Egypt
Kazura, James W.
United States, Cleveland
Case School of Medicine
Stoneking, Mark
Germany, Leipzig
Max-planck-institut Für Evolutionäre Anthropologie
Zimmerman, Peter A.
United States, Cleveland
Case School of Medicine
Statistics
Citations: 86
Authors: 13
Affiliations: 9
Identifiers
Doi:
10.1128/AAC.00089-08
ISSN:
00664804
Research Areas
Genetics And Genomics
Infectious Diseases