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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum
Nature, Volume 345, No. 6272, Year 1990
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Description
THE lethal form of human malaria caused by Plasmodium falciparum is virtually uncontrollable in many areas because of the development of drug resistance, in particular chloroquine resistance (CQR). CQR is biologically similar to the multiple drug resistance phenotype (MDR) of mammalian tumour cells, as both involve expulsion of drug from the cell and both can be reversed by calcium channel antagonists1. A homologue (pfmdr1) of the mammalian multidrug resistance gene has been implicated in CQR because it is amplified in some CQR isolates of P. falciparum2,3 as is an mdr gene in MDR tumour cells4. We show here that the complete sequences of pfmdr1 genes from 2 CQ sensitive (CQS) P. falciparum isolates are identical. In 5 CQR isolates, 1-4 key nucleotide differences resulted in amino acid substitutions. On the basis of these substitutions, we have correctly predicted the CQS/CQR status of a further 34 out of 36 isolates. This is a paradox as CQR arises much less frequently than would be predicted if single point mutations were sufficient. We conclude that a mutated pfmdr1 gene is one of at least two mutated genes required for CQR. © 1990 Nature Publishing Group.
Authors & Co-Authors
Foote, Simon J.
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Kyle, Dennis E.
United States, Silver Spring
Walter Reed Army Institute of Research
Martin, Rodger K.
United States, Silver Spring
Walter Reed Army Institute of Research
Oduola, Ayoade M.J.
United States, Silver Spring
Walter Reed Army Institute of Research
Day, Karen P.
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Kemp, David J.
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Cowman, Alan F.
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Statistics
Citations: 524
Authors: 7
Affiliations: 2
Identifiers
Doi:
10.1038/345255a0
ISSN:
00280836
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases