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Low linkage disequilibrium in wild Anopheles gambiae s.l. populations.

ABSTRACT: BACKGROUND: In the malaria vector Anopheles gambiae, understanding diversity in natural populations and genetic components of important phenotypes such as resistance to malaria infection is crucial for developing new malaria transmission blocking strategies. The design and interpretation of many studies here depends critically on Linkage disequilibrium (LD). For example in association studies, LD determines the density of Single Nucleotide Polymorphisms (SNPs) to be genotyped to represent the majority of the genomic information. Here, we aim to determine LD in wild An. gambiae s.l. populations in 4 genes potentially involved in mosquito immune responses against pathogens (Gambicin, NOS, REL2 and FBN9) using previously published and newly generated sequences. RESULTS: The level of LD between SNP pairs in cloned sequences of each gene was determined for 7 species (or incipient species) of the An. gambiae complex. In all tested genes and species, LD between SNPs was low: even at short distances (< 200 bp), most SNP pairs gave an r2 < 0.3. Mean r2 ranged from 0.073 to 0.766. In most genes and species LD decayed very rapidly with increasing inter-marker distance. CONCLUSIONS: These results are of great interest for the development of large scale polymorphism studies, as LD generally falls below any useful limit. It indicates that very fine scale SNP detection will be required to give an overall view of genome-wide polymorphism. Perhaps a more feasible approach to genome wide association studies is to use targeted approaches using candidate gene selection to detect association to phenotypes of interest.

SUBMITTER: Harris C

PROVIDER: S-EPMC2949739 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Low linkage disequilibrium in wild Anopheles gambiae s.l. populations.

Harris Caroline C Rousset François F Morlais Isabelle I Fontenille Didier D Cohuet Anna A

BMC genetics 20100915

<h4>Background</h4>In the malaria vector Anopheles gambiae, understanding diversity in natural populations and genetic components of important phenotypes such as resistance to malaria infection is crucial for developing new malaria transmission blocking strategies. The design and interpretation of many studies here depends critically on Linkage disequilibrium (LD). For example in association studies, LD determines the density of Single Nucleotide Polymorphisms (SNPs) to be genotyped to represent ...[more]

PMID: 20843306

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Project description:BackgroundVector control activities, namely long-lasting insecticidal nets (LLIN) and indoor residual spraying (IRS), have contributed significantly to the decreasing malaria burden observed in The Gambia since 2008. Nevertheless, insecticide resistance may threaten such success; it is important to regularly assess the susceptibility of local malaria vectors to available insecticides.MethodsIn the transmission seasons of 2016 and 2017, Anopheles gambiae (s.l.) larvae were sampled in or around the nine vector surveillance sentinel sites of the Gambia National Malaria Control Programme (GNMCP) and in a few additional sampling points. Using WHO susceptibility bioassays, female adult mosquitoes were exposed to insecticide-impregnated papers. Molecular identification of sibling species and insecticide resistance molecular markers was done on a subset of 2000 female mosquitoes.ResultsA total of 4666 wild-caught female adult mosquitoes were exposed to either permethrin (n = 665), deltamethrin (n = 744), DDT (n = 1021), bendiocarb (n = 990) or pirimiphos-methyl (n = 630) insecticide-impregnated papers and control papers (n = 616). Among the 2000 anophelines, 1511 (80.7%) were Anopheles arabiensis, 204 (10.9%) Anopheles coluzzii, 75 (4%) Anopheles gambiae (s.s.), and 83 (4.4%) An. gambiae (s.s.) and An. coluzzii hybrids. There was a significant variation in the composition and species distribution by regions and year, P = 0.009. Deltamethrin, permethrin and DDT resistance was found in An. arabiensis, especially in the coastal region, and was mediated by Vgsc-1014F/S mutations (odds ratio = 34, P = 0.014). There was suspected resistance to pirimiphos-methyl (actellic 300CS) in the North Bank Region although only one survivor had the Ace-1-119S mutation.ConclusionsAs no confirmed resistance to bendiocarb and actellic 300CS was detected, the national malaria control programme can continue using these insecticides for IRS. Nevertheless, the detection of Ace-1 119S mutation warrants extensive monitoring. The source of insecticide pressure driving insecticide resistance to pyrethroids and DDT detected at the coastal region should be further investigated in order to properly manage the spread of resistance in The Gambia.

Project description:BackgroundInsecticide resistance of Anopheles gambiae (s.l.) against public health insecticides is increasingly reported in Ghana and need to be closely monitored. This study investigated the intensity of insecticide resistance of An. gambiae (s.l.) found in a vegetable growing area in Accra, Ghana, where insecticides, herbicides and fertilizers are massively used for plant protection. The bioefficacy of long-lasting insecticidal nets (LLINs) currently distributed in the country was also assessed to delimitate the impact of the insecticide resistance intensity on the effectiveness of those nets.MethodsThree- to five-day-old adult mosquitoes that emerged from collected larvae from Opeibea, Accra (Ghana), were assayed using CDC bottle and WHO tube intensity assays against different insecticides. The Vgsc-L1014F and ace-1 mutations within the population were also characterized using PCR methods. Furthermore, cone bioassays against different types of LLINs were conducted to evaluate the extent and impact of the resistance of An. gambiae (s.l.) from Opeibea.ResultsAnopheles gambiae (s.l.) from Opeibea were resistant to all the insecticides tested with very low mortality observed against organochlorine, carbamates and pyrethroid insecticides using WHO susceptibility tests at diagnostic doses during three consecutive years of monitoring. The average frequencies of Vgsc-1014F and ace-1 in the An. gambiae (s.l.) population tested were 0.99 and 0.76, respectively. The intensity assays using both CDC bottle and WHO tubes showed high resistance intensity to pyrethroids and carbamates with survivals at 10× the diagnostic doses of the insecticides tested. Only pirimiphos methyl recorded a low resistance intensity with 100% mortality at 5× the diagnostic dose. The bioefficacy of pyrethroid LLINs ranged from 2.2 to 16.2% mortality while the PBO LLIN, PermaNet® 3.0, was 73%.ConclusionsWHO susceptibility tests using the diagnostic doses described the susceptibility status of the mosquito colony while CDC bottle and WHO tube intensity assays showed varying degrees of resistance intensity. Although both methods are not directly comparable, the indication of the resistance intensity showed the alarming insecticide resistance intensity in Opeibea and its surroundings, which could have an operational impact on the efficacy of vector control tools and particularly on pyrethroid LLINs.

Project description:BackgroundUnderstanding the age-structure of mosquito populations, especially malaria vectors such as Anopheles gambiae, is important for assessing the risk of infectious mosquitoes, and how vector control interventions may impact this risk. The use of near-infrared spectroscopy (NIRS) for age-grading has been demonstrated previously on laboratory and semi-field mosquitoes, but to date has not been utilized on wild-caught mosquitoes whose age is externally validated via parity status or parasite infection stage. In this study, we developed regression and classification models using NIRS on datasets of wild An. gambiae (s.l.) reared from larvae collected from the field in Burkina Faso, and two laboratory strains. We compared the accuracy of these models for predicting the ages of wild-caught mosquitoes that had been scored for their parity status as well as for positivity for Plasmodium sporozoites.ResultsRegression models utilizing variable selection increased predictive accuracy over the more common full-spectrum partial least squares (PLS) approach for cross-validation of the datasets, validation, and independent test sets. Models produced from datasets that included the greatest range of mosquito samples (i.e. different sampling locations and times) had the highest predictive accuracy on independent testing sets, though overall accuracy on these samples was low. For classification, we found that intramodel accuracy ranged between 73.5-97.0% for grouping of mosquitoes into "early" and "late" age classes, with the highest prediction accuracy found in laboratory colonized mosquitoes. However, this accuracy was decreased on test sets, with the highest classification of an independent set of wild-caught larvae reared to set ages being 69.6%.ConclusionsVariation in NIRS data, likely from dietary, genetic, and other factors limits the accuracy of this technique with wild-caught mosquitoes. Alternative algorithms may help improve prediction accuracy, but care should be taken to either maximize variety in models or minimize confounders.

Project description:BACKGROUND: The operational impact of insecticide resistance on the effectiveness of long-lasting insecticide nets (LLINs) and indoor residual spraying (IRS) is poorly understood. One factor which may prolong the effectiveness of these tools in the field is the increase in insecticide susceptibility with mosquito age. In this study, LLINs and IRS were tested against young (three to five days) and old (17-19 days) pyrethroid resistant Anopheles gambiae s.l. from Burkina Faso. METHODS: Blood-fed adult Anopheles gambiae s.l. were collected from south-west Burkina Faso and identified to species/form level. Cohorts of the F1 progeny of An. gambiae s.s. S-forms were exposed to deltamethrin (0.05%) at three to five or 17-19 days post-emergence and tested for the frequency of the resistance allele 1014F. Isofemale lines of the M, S- form of An. gambiae s.s. and Anopheles arabiensis were exposed in WHO cone tests to either a) LLINs deployed in households for two years or (b) bendiocarb sprayed walls. RESULTS: Mortality rates in response to deltamethrin (0.05%) increased from levels indicative of strong resistance in three to five day old F1 mosquitoes, to near full susceptibility in the 17-19 day old cohort. On exposure to LLINs sampled from the field, the mortality rate in isofemale lines was higher in older mosquitoes than young (OR = 5.28, CI 95% = 2.81-9.92), although the mortality estimates were affected by the LLIN tested. In general, the LLINs sampled from the field performed poorly in WHO cone bioassays using either laboratory susceptible or field caught mosquito populations. Finally, there was a clear relationship between mortality and age on exposure to bendiocarb-sprayed walls, with older mosquitoes again proving more susceptible (OR = 3.39, CI 95% = 2.35-4.90). CONCLUSIONS: Age is a key factor determining the susceptibility of mosquitoes to insecticides, not only in laboratory studies, but in response to field-based vector control interventions. This has important implications for understanding the epidemiological impact of resistance. If mosquitoes old enough to transmit malaria are still being suppressed with available insecticides, is resistance potentially having less of an impact than often assumed? However, the poor performance of LLINs used in this study in Burkina Faso, is a cause for concern and requires urgent investigation.

Dataset Information

Low linkage disequilibrium in wild Anopheles gambiae s.l. populations.

Publications

Low linkage disequilibrium in wild Anopheles gambiae s.l. populations.

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