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Data from: Positional cloning of rp2 QTL associates the P450 genes CYP6Z1, CYP6Z3 and CYP6M7 with pyrethroid resistance in the malaria vector Anopheles funestus

Citation

Irving, Helen et al. (2012), Data from: Positional cloning of rp2 QTL associates the P450 genes CYP6Z1, CYP6Z3 and CYP6M7 with pyrethroid resistance in the malaria vector Anopheles funestus, Dryad, Dataset, https://doi.org/10.5061/dryad.v218g

Abstract

Pyrethroid resistance in Anopheles funestus is threatening malaria control in Africa. Elucidation of underlying resistance mechanisms is crucial to improve the success of future control programs. A positional cloning approach was used to identify genes conferring resistance in the uncharacterised rp2 QTL previously detected in this vector using F6 Advanced Intercross Lines (AIL). A 113 kb BAC clone spanning rp2 was identified and sequenced revealing a cluster of fifteen P450 genes and one salivary protein gene (SG7-2). Contrary to An. gambiae, AfCYP6M1 is triplicated in An. funestus while AgCYP6Z2 ortholog is absent. 565 new SNPs were identified for genetic mapping from rp2 P450s and other genes revealing high genetic polymorphisms with 1 SNP every 36bp. A significant genotype/phenotype association was detected for rp2 P450s but not for a cluster of cuticular protein genes previously associated with resistance in An. gambiae. QTL mapping using F6 AIL confirms the rp2 QTL with an increase logarithm of odds (LOD) score of 5. Multiplex gene expression profiling of 15 P450s and other genes around rp2 followed by individual validation using qRT-PCR indicated a significant over-expression in the resistant FUMOZ-R strain of the P450s AfCYP6Z1, AfCYP6Z3, AfCYP6M7 and the glutathione-s-transferase GSTe2 with respective fold-change of 11.2, 6.3, 5.5 and 2.8. Polymorphisms analysis of AfCYP6Z1 and AfCYP6Z3 identified amino acid changes potentially associated with resistance further indicating that these genes are controlling the pyrethroid resistance explained by the rp2 QTL. The characterisation of this rp2 QTL significantly improves our understanding of resistance mechanisms in An. funestus.

Usage Notes

Location

Africa