Abstract
BackgroundGenetic linkage mapping identified a region of chromosome 2L in the Anopheles gambiae genome that exerts major control over natural infection by Plasmodium falciparum. This 2L Plasmodium-resistance interval was mapped in mosquitoes from a natural population in Mali, West Africa, and controls the numbers of P. falciparum oocysts that develop on the vector midgut. An important question is whether genetic variation with respect to Plasmodium-resistance exists across Africa, and if so whether the same or multiple geographically distinct resistance mechanisms are responsible for the trait.MethodsTo identify P falciparum resistance loci in pedigrees generated and infected in Kenya, East Africa, 28 microsatellite loci were typed across the mosquito genome. Genetic linkage mapping was used to detect significant linkage between genotype and numbers of midgut oocysts surviving to 7–8 days post-infection.ResultsA major malaria-control locus was identified on chromosome 2L in East African mosquitoes, in the same apparent position originally identified from the West African population. Presence of this resistance locus explains 75% of parasite free mosquitoes. The Kenyan resistance locus is named EA_Pfin1 (East Africa_ Plasmodium falciparum Infection Intensity).ConclusionDetection of a malaria-control locus at the same chromosomal location in both East and West African mosquitoes indicates that, to the level of genetic resolution of the analysis, the same mechanism of Plasmodium-resistance, or a mechanism controlled by the same genomic region, is found across Africa, and thus probably operates in A. gambiae throughout its entire range.
Highlights
Genetic linkage mapping identified a region of chromosome 2L in the Anopheles gambiae genome that exerts major control over natural infection by Plasmodium falciparum
It would be valuable to know whether the genetic mechanism of the Plasmodium-resistance island (PRI) identified in Mali is specific to that population, suggesting that there might be many geographically local A. gambiae resistance mechanisms across Africa, or whether the mechanism identified by the PRI exists in A. gambiae throughout Africa
Detection of linkage required the larger sample size obtained by combining groups of mosquitoes that fed on at least two different parasite isolates, and the signal must have originated in the pedigree's consistent genetic response to at least two different parasite isolates. These results indicate that Plasmodium resistance controlled by the A. gambiae EA_Pfin1 locus can be independent of and transcend parasite genotype
Summary
Genetic linkage mapping identified a region of chromosome 2L in the Anopheles gambiae genome that exerts major control over natural infection by Plasmodium falciparum. This 2L Plasmodium-resistance interval was mapped in mosquitoes from a natural population in Mali, West Africa, and controls the numbers of P. falciparum oocysts that develop on the vector midgut. The genetics of natural vector resistance to P. falciparum is dissected, with the ultimate goal to utilize successful existing natural Plasmodium resistance mechanisms for control of human malaria transmission. A recent comprehensive study reported the prevalence, strength and genomic location of natural P. falciparum resistance loci in A. gambiae in Mali, West Africa [4]. A major barrier to gene flow in A. gambiae occurs between West and East African populations [5], and comparing these populations should offer the most stringent test of the geographic generality of genetic loci controlling resistance mechanisms
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
