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Association Mapping of Insecticide Resistance in Wild Anopheles gambiae Populations: Major Variants Identified in a Low-Linkage Disequilbrium Genome

Weetman, D and Wilding, CS and Steen, K and Morgan, JC and Simard, F and Donnelly, MJ (2010) Association Mapping of Insecticide Resistance in Wild Anopheles gambiae Populations: Major Variants Identified in a Low-Linkage Disequilbrium Genome. PLOS ONE, 5 (10). e13140-e13140. ISSN 1932-6203

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Abstract

Background: Association studies are a promising way to uncover the genetic basis of complex traits in wild populations. Data on population stratification, linkage disequilibrium and distribution of variant effect-sizes for different trait-types are required to predict study success but are lacking for most taxa. We quantified and investigated the impacts of these key variables in a large-scale association study of a strongly selected trait of medical importance: pyrethroid resistance in the African malaria vector Anopheles gambiae.
Methodology/Principal Findings: We genotyped <1500 resistance-phenotyped wild mosquitoes from Ghana and
Cameroon using a 1536-SNP array enriched for candidate insecticide resistance gene SNPs. Three factors greatly impacted study power. (1) Population stratification, which was attributable to co-occurrence of molecular forms (M and S), and cryptic within-form stratification necessitating both a partitioned analysis and genomic control. (2) All SNPs of substantial effect (odds ratio, OR.2) were rare (minor allele frequency, MAF,0.05). (3) Linkage disequilibrium (LD) was very low throughout most of the genome. Nevertheless, locally high LD, consistent with a recent selective sweep, and uniformly high ORs in each subsample facilitated significant direct and indirect detection of the known insecticide target site mutation kdr L1014F (OR<6; P,1026), but with resistance level modified by local haplotypic background.
Conclusion: Primarily as a result of very low LD in wild A. Gambiae, LD-based association mapping is challenging, but is feasible at least for major effect variants, especially where LD is enhanced by selective sweeps. Such variants will be of greatest importance for predictive diagnostic screening.

Item Type: Article
Uncontrolled Keywords: MD Multidisciplinary
Subjects: Q Science > QL Zoology
Divisions: Natural Sciences and Psychology
Publisher: PUBLIC LIBRARY SCIENCE
Related URLs:
Date Deposited: 18 Jan 2016 11:17
Last Modified: 11 Sep 2017 08:48
DOI or Identification number: 10.1371/journal.pone.0013140
URI: http://researchonline.ljmu.ac.uk/id/eprint/2643

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