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Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector

Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673, Irving, Helen, Morgan, John, Lobo, N. F., Collins, F. H., Hunt, R. H., Coetzee, M., Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173 and Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247 (2009) 'Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector'. Genome Research, Vol 19, Issue 3, pp. 452-459.

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Abstract

Pyrethroid resistance in Anopheles funestus is a potential obstacle to malaria control in Africa. Tools are needed to detect resistance in field populations. We have been using a positional cloning approach to identify the major genes conferring pyrethroid resistance in this vector. A quantitative trait locus (QTL) named rp1 explains 87% of the genetic variance in pyrethroid susceptibility in two families from reciprocal crosses between susceptible and resistant strains. Two additional QTLs of minor effect, rp2 and rp3, were also detected. We sequenced a 120-kb BAC clone spanning the rp1 QTL and identified 14 protein-coding genes and one putative pseudogene. Ten of the 14 genes encoded cytochrome P450s, and expression analysis indicated that four of these P450s were differentially expressed between susceptible and resistant strains. Furthermore, two of these genes, CYP6P9 and CYP6P4, which are 25 and 51 times overexpressed in resistant females, are tandemly duplicated in the BAC clone as well as in laboratory and field samples, suggesting that P450 gene duplication could contribute to pyrethroid resistance in An. funestus. Single nucleotide polymorphisms (SNPs) were identified within CYP6P9 and CYP6P4, and genotyping of the progeny of the genetic crosses revealed a maximum penetrance value f(2) = 1, confirming that these SNPs are valid resistance markers in the laboratory strains. This serves as proof of principle that a DNA-based diagnostic test could be designed to trace metabolic resistance in field populations. This will be a major advance for insecticide resistance management in malaria vectors, which requires the early detection of resistance alleles.

Item Type: Article
Uncontrolled Keywords: insecticide resistance drosophila-melanogaster cytochrome-p450 genes quantitative traits over-expression south-africa gambiae culicidae sequence diptera
Subjects: WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
QU Biochemistry > Genetics > QU 450 General Works
QV Pharmacology > QV 38 Drug action.
QX Parasitology > Insects. Other Parasites > QX 515 Anopheles
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
QX Parasitology > Insects. Other Parasites > QX 505 Diptera
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
Faculty: Department: Groups (2002 - 2012) > Vector Group
Digital Object Identifer (DOI): https://doi.org/10.1101/gr.087916.108
Depositing User: Users 183 not found.
Date Deposited: 10 Mar 2010 14:17
Last Modified: 06 Feb 2018 13:00
URI: http://archive.lstmed.ac.uk/id/eprint/413

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