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

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Irving, Helen, Riveron Miranda, Jacob ORCID: https://orcid.org/0000-0002-5395-767X, Ibrahim, SulaimanSadi, Lobo, N.F. and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2012) 'Positional cloning of rp2 QTL associates the P450 genes CYP6Z1, CYP6Z3 and CYP6M7 with pyrethroid resistance in the malaria vector Anopheles funestus'. Heredity, Vol 109, Issue 6, pp. 383-392.

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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 quantitative trait locus (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 15 P450 genes and one salivary protein gene (SG7-2). Contrary to A. gambiae, AfCYP6M1 is triplicated in A. funestus, while AgCYP6Z2 orthologue is absent. Five hundred and sixty-five new single nucleotide polymorphisms (SNPs)were identified for genetic mapping from rp2 P450s and other genes revealing high genetic polymorphisms with one SNP every 36 bp. A significant genotype/phenotype association was detected for rp2 P450s but not for a cluster of cuticular
protein genes previously associated with resistance in A. gambiae. QTL mapping using F6 AIL confirms the rp2 QTL with
an increase logarithm of odds 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 overexpression 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 A. funestus.

Item Type: Article
Additional Information: The electronic version of this article is the original and can be found at: http://dx.doi.org/10.1038/hdy.2012.53
Uncontrolled Keywords: Anopheles funestus; malaria; insecticide resistance; QTL mapping; P450s
Subjects: QU Biochemistry > Genetics > QU 450 General Works
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
Faculty: Department: Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI): https://doi.org/10.1038/hdy.2012.53
Depositing User: Users 183 not found.
Date Deposited: 10 Dec 2012 12:20
Last Modified: 13 Sep 2019 15:47
URI: https://archive.lstmed.ac.uk/id/eprint/3019

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