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. 2007 Jan 29:8:34.
doi: 10.1186/1471-2164-8-34.

Mapping a quantitative trait locus (QTL) conferring pyrethroid resistance in the African malaria vector Anopheles funestus

Charles S Wondji  1 , John Morgan, Maureen Coetzee, Richard H Hunt, Keith Steen, William C Black 4th, Janet Hemingway, Hilary Ranson
Affiliations

Mapping a quantitative trait locus (QTL) conferring pyrethroid resistance in the African malaria vector Anopheles funestus

Charles S Wondji et al. BMC Genomics. .

Abstract

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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Genetic map of An. funestus using the combined data from the 11 families. A scale of genetic distance in centimorgans is shown.
Figure 2
Figure 2
Plot of mortality rate as a function of alleles inherited from the susceptible parent in family 4 for significant markers on chromosome 2.
Figure 3
Figure 3
Plot of mortality rate as a function of alleles inherited from the susceptible parent in family 11 for significant markers on chromosome 2.
Figure 4
Figure 4
Plot of LOD scores associated with pyrethroid resistance on chromosomes X, 2 and 3 in family 4. Solid lines represent LOD estimated by composite-interval mapping and dashed lines represent LOD estimated by interval mapping. The straight line along the top of each graph represents the threshold value for LOD. Names of markers are listed on chromosome 2 to orient QTL position.
Figure 5
Figure 5
Plot of LOD scores associated with pyrethroid resistance on chromosomes 2 and 3 in family11. Solid lines represent LOD estimated by interval mapping and dashed lines represent LOD estimated by composite-interval mapping. The straight line along the top of each graph represents the threshold value for LOD. Names of markers are listed only on chromosome 2 to orient the unique QTL position.
Figure 6
Figure 6
Cytogenetic map of An. funestus polytene chromosomes indicating rp1 QTL position and P450 genes and insecticide target site genes, physically mapped by in situ hybridisation during this study. This figure is adapted from [39].
See this image and copyright information in PMC

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