title: Identification and distribution of a GABA receptor mutation conferring dieldrin resistance in the malaria vector Anopheles funestus in Africa.
abstract: Growing problems of pyrethroid resistance in Anopheles funestus have intensified efforts to identify alternative insecticides. Many agrochemicals target the GABA receptors, but cross-resistance from dieldrin resistance may preclude their introduction. Dieldrin resistance was detected in An. funestus populations from West (Burkina Faso) and central (Cameroon) Africa, but populations from East (Uganda) and Southern Africa (Mozambique and Malawi) were fully susceptible to this insecticide. Partial sequencing of the dieldrin target site, the γ-aminobutyric acid (GABA) receptor, identified two amino acid substitutions, A296S and V327I. The A296S mutation has been associated with dieldrin resistance in other species. The V327I mutations was detected in the resistant sample from Burkina Faso and Cameroon and consistently associated with the A296S substitution. The full-length of the An. funestus GABA-receptor gene, amplified by RT-PCR, generated a sequence of 1674 bp encoding 557 amino acid of the protein in An. funestus with 98% similarity to that of Anopheles gambiae. Two diagnostic assays were developed to genotype the A296S mutation (pyrosequencing and PCR-RFLP), and use of these assays revealed high frequency of the resistant allele in Burkina Faso (60%) and Cameroon (82%), moderate level in Benin (16%) while low frequency or absence of the mutation was observed respectively in Uganda (7.5%) or 0% in Malawi and Mozambique. The distribution of the Rdl(R) mutation in An. funestus populations in Africa suggests extensive barriers to gene flow between populations from different regions.
authors.affiliation: Vector Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom. c.s.wondji@liverpool.ac.uk
authors.forename: Charles S
authors.initials: CS
authors.lastname: Wondji
authors.forename: Roch K
authors.initials: RK
authors.lastname: Dabire
authors.forename: Zainab
authors.initials: Z
authors.lastname: Tukur
authors.forename: Helen
authors.initials: H
authors.lastname: Irving
authors.forename: Rousseau
authors.initials: R
authors.lastname: Djouaka
authors.forename: John C
authors.initials: JC
authors.lastname: Morgan
mesh_terms: D000349:Africa; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D004026:Dieldrin / Q000494:pharmacology*; D005838:Genotype; D007300:Insect Control / Q000379:methods; D007303:Insect Vectors / Q000187:drug effects / Q000235:genetics; D007305:Insecticide Resistance / Q000187:drug effects / Q000235:genetics; D007306:Insecticides / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000469:parasitology; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects; D058974:Phylogeography; D010963:Plasmodium falciparum / Q000502:physiology; D012150:Polymorphism, Restriction Fragment Length; D011485:Protein Binding / Q000187:drug effects*; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D007306:Insecticides; D018079:Receptors, GABA; D004026:Dieldrin