Back to Search
Start Over
Dissecting the loci of low-level quinine resistance in malaria parasites.
- Source :
-
Molecular microbiology [Mol Microbiol] 2004 May; Vol. 52 (4), pp. 985-97. - Publication Year :
- 2004
-
Abstract
- Quinine (QN) remains effective against Plasmodium falciparum, but its decreasing efficacy is documented from different continents. Multiple genes are likely to contribute to the evolution of QN resistance. To locate genes contributing to QN response variation, we have searched a P. falciparum genetic cross for quantitative trait loci (QTL). Results identify additive QTL in segments of chromosomes (Chrs) 13, 7 and 5, and pairwise effects from two additional loci of Chrs 9 and 6 that interact, respectively, with the QTL of Chrs 13 and 7. The mapped segments of Chrs 7 and 5 contain pfcrt, the determinant of chloroquine resistance (CQR), and pfmdr1, a gene known to affect QN responses. Association of pfcrt with a QTL of QN resistance supports anecdotal evidence for an evolutionary relationship between CQR and reduced QN sensitivity. The Chr 13 segment contains several candidate genes, one of which (pfnhe-1) encodes a putative Na(+)/H(+) exchanger. A repeat polymorphism in pfnhe-1 shows significant association with low QN response in a collection of P. falciparum strains from Asia, Africa and Central and South America. Dissection of the genes and modifiers involved in QN response will require experimental strategies that can evaluate multiple genes from different chromosomes in combination.
- Subjects :
- ATP-Binding Cassette Transporters genetics
ATP-Binding Cassette Transporters physiology
Amino Acid Sequence
Animals
Antimalarials pharmacology
Chloroquine pharmacology
Chromosome Mapping
Genes, Protozoan
Membrane Proteins genetics
Membrane Proteins physiology
Membrane Transport Proteins
Molecular Sequence Data
Multifactorial Inheritance
Plasmodium falciparum drug effects
Polymorphism, Genetic
Protozoan Proteins genetics
Protozoan Proteins physiology
Quantitative Trait Loci
Quantitative Trait, Heritable
Repetitive Sequences, Nucleic Acid
Sodium-Hydrogen Exchangers genetics
Sodium-Hydrogen Exchangers physiology
Drug Resistance genetics
Plasmodium falciparum genetics
Quinine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0950-382X
- Volume :
- 52
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 15130119
- Full Text :
- https://doi.org/10.1111/j.1365-2958.2004.04035.x