Abstract
Chloroquine resistance in a P. falciparum cross maps as a Mendelian trait to a 36 kb segment of chromosome 7. This segment harbors cg2, a gene encoding a unique approximately 330 kDa protein with complex polymorphisms. A specific set of polymorphisms in 20 chloroquine-resistant parasites from Asia and Africa, in contrast with numerous differences in 21 sensitive parasites, suggests selection of a cg2 allele originating in Indochina over 40 years ago. One chloroquine-sensitive clone exhibited this allele, suggesting another resistance component. South American parasites have cg2 polymorphisms consistent with a separate origin of resistance. CG2 protein is found at the parasite periphery, a site of chloroquine transport, and in association with hemozoin of the digestive vacuole, where chloroquine inhibits heme polymerization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Africa
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Amino Acid Sequence
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Animals
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Antimalarials / pharmacology*
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Asia, Southeastern
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Chloroquine / pharmacology*
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Chromosome Mapping
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Crossing Over, Genetic
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DNA, Protozoan / analysis
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DNA, Satellite / analysis
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Drug Resistance, Microbial
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Erythrocytes / parasitology
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Genetic Linkage
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Molecular Sequence Data
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Pan troglodytes
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / genetics*
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Polymorphism, Genetic
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Protozoan Proteins / analysis
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Protozoan Proteins / genetics*
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Sequence Analysis, DNA
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Transcription, Genetic
Substances
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Antimalarials
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CG1 protein, Plasmodium falciparum
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CG2 protein, Plasmodium falciparum
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DNA, Protozoan
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DNA, Satellite
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Protozoan Proteins
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Chloroquine
Associated data
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GENBANK/AF030690
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GENBANK/AF030691
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GENBANK/AF030692
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GENBANK/AF030693
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GENBANK/AF030694
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GENBANK/AF033378