Dissecting the Genetic Basis of Resistance to Malaria Parasites in Anopheles gambiae
Stephanie A. Blandin,1,2,*
Rui Wang-Sattler,1,3,*
Marina Lamacchia,2
Julien Gagneur,1
Gareth Lycett,1,
Ye Ning,1,
Elena A. Levashina,2
Lars M. Steinmetz1,
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.
2 CNRS UPR9022, INSERM U963, 15 rue Descartes, 67084 Strasbourg, France.
3 Institute of Epidemiology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764 Munich/Neuherberg, Germany.
* These authors contributed equally to this work.
Present address: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Present address: Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, 1870 Frederiksberg C, Denmark.
To whom correspondence should be addressed. E-mail: larsms{at}embl.de
