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Title: Investigating the genetic basis of pyrethroid resistance in two members of the Anopheles gambiae complex
Author: Witzig, Claudia
ISNI:       0000 0004 2729 0191
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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Chemical control of mosquito vectors, via indoor residual spraying or insecticide treated bed nets, is an integral component of malaria control strategies. Limited availability of insecticides licensed for public health and the rapid development of resistance in mosquito populations to these insecticides, in particular to some pyrethroids, may compromise vector control efforts. With the exception of mutations in the insecticide target sites, relatively little is known about the genetics of pyrethroid resistance in malaria vectors. In some populations candidate effector genes, e.g. cyp6p3 or cyp6m2 in An. gambiae s.s. from Akron, Benin, have been identified as being over expressed in resistant strains but the underlying mechanisms responsible for the increased expression remain unknown. In this study, a combination of quantitative PCR, genetic mapping and microarray tools were used to investigate the mechanisms responsible for pyrethroid resistance in two African major malaria vectors, Anopheles gambiae and An. arabiensis. The current work was unable to confirm an association of these known candidates in either a laboratory colony established from Akron or in recent field caught material. Therefore a genetic mapping approach was adopted using field collected mated females to generate F2 isofemale lines. A major QTL on chromosome 3R was identified which coincides with a genomic region previously implicated in pyrethroid resistance in East African populations. This is the first genetic mapping of insecticide resistance using natural out-bred populations of Anopheles and the advantages and limitations of this approach are discussed. In a second experiment, genetic loci involved in permethrin resistance in An. arabiensis were mapped by establishing genetic crosses between a permethrin resistant strain from Chad and a susceptible strain from Mozambique. A single QTL on chromosome 2R was identified in the F2 progeny that accounts for ~24% of the phenotypic variance. This QTL coincides with a large cluster of detoxification genes. Pyrethroid resistance is not associated with target-site mutations in this population. Finally, microarrays were used to identify genes differentially expressed between a backcross population, generated by crossing the F1 population from the resistant Chad strain and the susceptible Mozambique strain of An. arabiensis back to the parental resistant strain, with the susceptible strain. A number of candidate genes were identified, including the P450 genes cyp4h24 and cyp9j5, but neither of these were located within the boundaries of the QTL on 2R. These findings support the presence of metabolic resistance in this population and fine mapping of the identified QTL as well as further investigation of the microarray hits is warranted.
Supervisor: Ranson, Hilary; Wondji, Charles; Strode, Clare Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics ; R Medicine (General)