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• W2022376775 abstract "Genetic modification of malaria parasites is becoming more facile and the range of available manipulations is slowly increasing. Depending on the species, we can now do single and double crossover homologous recombination [ 1 Carvalho T.G. Ménard R. Manipulating the Plasmodium genome. Curr. Issues Mol. Biol. 2005; 7: 39-55 PubMed Google Scholar ], regulated expression modulated at the replication, transcription or protein stability levels [ 2 de Koning-Ward T.F. Gilson P.R. Keeping it simple: an easy method for manipulating the expression levels of malaria proteins. Trends Parasitol. 2009; 25: 4-7 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar ], stage-specific recombination [ 3 Carvalho T.G. et al. Conditional mutagenesis using site-specific recombination in Plasmodium berghei. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 14931-14936 Crossref PubMed Scopus (49) Google Scholar ] and transposon insertion [ 4 Sakamoto H. et al. Conditional mutagenesis using site-specific recombination in Plasmodium berghei. Nucleic Acids Res. 2005; 33: e174 Crossref PubMed Scopus (18) Google Scholar , 5 Nkrumah L.J. et al. Efficient site-specific integration in Plasmodium falciparum chromosomes mediated by mycobacteriophage Bxb1 integrase. Nat. Methods. 2006; 3: 615-621 Crossref PubMed Scopus (170) Google Scholar , 6 Balu B. et al. piggyBac is an effective tool for functional analysis of the Plasmodium falciparum genome. BMC Microbiol. 2009; 9: 83 Crossref PubMed Scopus (53) Google Scholar ]. The number of gene knockouts reported in the literature is now in the hundreds [ 7 Maier A.G. et al. Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell. 2008; 134: 48-61 Abstract Full Text Full Text PDF PubMed Scopus (369) Google Scholar ], many with interesting phenotypes that inform on gene function. The first complementation of a knockout clone was reported in 2001 [ 8 Sultan A.A. et al. Complementation of Plasmodium berghei TRAP knockout parasites using human dihydrofolate reductase gene as a selectable marker. Mol. Biochem. Parasitol. 2001; 113: 151-156 Crossref PubMed Scopus (17) Google Scholar ], but since then only a handful of genetic complementations have been performed. The peril in this omission is that the manipulated parasites could have unintended mutations during selection [ 9 Dharia N.V. et al. Use of high-density tiling microarrays to identify mutations globally and elucidate mechanisms of drug resistance in Plasmodium falciparum. Genome Biol. 2009; 10: R21 Crossref PubMed Scopus (118) Google Scholar ] that contribute to the phenotype observed. Indeed, the phenotype of a mutant might be due to an unintended positional effect resulting from disruption of a locus. This has been known for a long time in other systems; complementation is de rigeur in many yeast and bacterial systems and it is now also possible to apply this principle to the Apicomplexan parasites Plasmodium and Toxoplasma." @default.
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• W2022376775 date "2011-01-01" @default.
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• W2022376775 title "Has the time come for us to complement our malaria parasites?" @default.
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