TY - JOUR T1 - Dissecting the Genetic Basis of Resistance to Malaria Parasites in <em>Anopheles gambiae</em> JF - Science JO - Science SP - 147 LP - 150 DO - 10.1126/science.1175241 VL - 326 IS - 5949 AU - Blandin, Stephanie A. AU - Wang-Sattler, Rui AU - Lamacchia, Marina AU - Gagneur, Julien AU - Lycett, Gareth AU - Ning, Ye AU - Levashina, Elena A. AU - Steinmetz, Lars M. Y1 - 2009/10/02 UR - http://science.sciencemag.org/content/326/5949/147.abstract N2 - Recent mapping of resistance alleles in the mosquito Anopheles gambiae that provide protection against the human malaria parasite Plasmodium falciparum revealed a major Plasmodium resistance island (PRI), comprising allelic versions of two leucine-rich repeat-containing proteins, LRIM1 and APL1, which form a complex with the complement C3-like protein TEP1. Using RNA interference inactivation of heterozygous allelic versions of TEP1 genes, Blandin et al. (p. 147) show that TEP1 heterogeneity reflects phenotypic variation among mosquito strains parasitized with the rodent malaria parasite Plasmodium berghei. It remains unclear whether the observed differences are the outcomes of different selection regimes, because of differing mechanisms, or because the complex is also used in other contexts.The ability of Anopheles gambiae mosquitoes to transmit Plasmodium parasites is highly variable between individuals. However, the genetic basis of this variability has remained unknown. We combined genome-wide mapping and reciprocal allele-specific RNA interference (rasRNAi) to identify the genomic locus that confers resistance to malaria parasites and demonstrated that polymorphisms in a single gene encoding the antiparasitic thioester-containing protein 1 (TEP1) explain a substantial part of the variability in parasite killing. The link between TEP1 alleles and resistance to malaria may offer new tools for controlling malaria transmission. The successful application of rasRNAi in Anopheles suggests that it could also be applied to other organisms where RNAi is feasible to dissect complex phenotypes to the level of individual quantitative trait alleles. ER -