Blandin Stephanie A, Wang-Sattler Rui, Lamacchia Marina, Gagneur Julien, Lycett Gareth, Ning Ye, Levashina Elena A, Steinmetz Lars M
European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Science. 2009 Oct 2;326(5949):147-50. doi: 10.1126/science.1175241.
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.
冈比亚按蚊传播疟原虫的能力在个体之间差异很大。然而,这种变异性的遗传基础仍然未知。我们结合全基因组定位和反向等位基因特异性RNA干扰(rasRNAi)来确定赋予对疟原虫抗性的基因组位点,并证明编码抗寄生虫含硫酯蛋白1(TEP1)的单个基因中的多态性解释了寄生虫杀伤变异性的很大一部分。TEP1等位基因与疟疾抗性之间的联系可能为控制疟疾传播提供新工具。rasRNAi在按蚊中的成功应用表明,它也可以应用于其他可行RNA干扰的生物体,以将复杂表型剖析到个体数量性状等位基因水平。