Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector
Genome Research, Volume 19, No. 3, Year 2009
Notification
URL copied to clipboard!
Description
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 rpl 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 rpl 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. © 2009 by Cold Spring Harbor Laboratory Press.
Authors & Co-Authors
Wondji, Charles Sinclair
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Irving, Helen
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Morgan, John C.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Lobo, Neil Francis
United States, Notre Dame
University of Notre Dame
Collins, Frank H.
United States, Notre Dame
University of Notre Dame
Hunt, Richard H.
South Africa, Johannesburg
University of the Witwatersrand
Coetzee, Maureen
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
National Institute for Communicable Diseases
Hemingway, Janet
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Ranson, Hilary A.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Statistics
Citations: 242
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.1101/gr.087916.108
ISSN:
10889051
e-ISSN:
15495469
Research Areas
Genetics And Genomics
Infectious Diseases
Noncommunicable Diseases
Study Approach
Quantitative
Participants Gender
Female