Mapping a quantitative trait locus (QTL) conferring pyrethroid resistance in the African malaria vector Anopheles funestus.
BACKGROUND
Pyrethroid resistance in Anopheles funestus populations has led to an increase in malaria transmission in southern Africa. Resistance has been attributed to elevated activities of cytochrome P450s but the molecular basis underlying this metabolic resistance is unknown. Microsatellite and SNP markers were used to construct a linkage map and to detect a quantitative trait locus (QTL) associated with pyrethroid resistance in the FUMOZ-R strain of An. funestus from Mozambique.


RESULTS
By genotyping 349 F2 individuals from 11 independent families, a single major QTL, rp1, at the telomeric end of chromosome 2R was identified. The rp1 QTL appears to present a major effect since it accounts for more than 60% of the variance in susceptibility to permethrin. This QTL has a strong additive genetic effect with respect to susceptibility. Candidate genes associated with pyrethroid resistance in other species were physically mapped to An. funestus polytene chromosomes. This showed that rp1 is genetically linked to a cluster of CYP6 cytochrome P450 genes located on division 9 of chromosome 2R and confirmed earlier reports that pyrethroid resistance in this strain is not associated with target site mutations (knockdown resistance).


CONCLUSIONS
We hypothesize that one or more of these CYP6 P450s clustered on chromosome 2R confers pyrethroid resistance in the FUMOZ-R strain of An. funestus.
Wondji
Charles S
CS
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. c.s.wondji@liverpool.ac.uk
Morgan
John
J
Coetzee
Maureen
M
Hunt
Richard H
RH
Steen
Keith
K
Black
William C
WC
Hemingway
Janet
J
Ranson
Hilary
H
D000110:Acetylcholinesterase / Q000235:genetics; D000349:Africa; D000818:Animals; D030801:Animals, Genetically Modified; D000852:Anopheles / Q000187:drug effects* / Q000235:genetics*; D002874:Chromosome Mapping; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005838:Genotype; D007305:Insecticide Resistance / Q000235:genetics; D008288:Malaria / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009073:Mozambique; D010641:Phenotype; D011722:Pyrethrins / Q000494:pharmacology*; D040641:Quantitative Trait Loci
D011722:Pyrethrins; D003577:Cytochrome P-450 Enzyme System; D000110:Acetylcholinesterase