Dissecting the genetic basis of resistance to malaria parasites in Anopheles gambiae.
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.
Blandin
Stephanie A
SA
European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Wang-Sattler
Rui
R
Lamacchia
Marina
M
Gagneur
Julien
J
Lycett
Gareth
G
Ning
Ye
Y
Levashina
Elena A
EA
Steinmetz
Lars M
LM
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D002874:Chromosome Mapping; D017344:Genes, Insect; D049750:Genome, Insect; D007113:Immunity, Innate; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism*; D007303:Insect Vectors / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D010962:Plasmodium berghei / Q000276:immunology / Q000502:physiology*; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D034622:RNA Interference
D019476:Insect Proteins; C544265:TEP1 protein, Anopheles gambiae