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

Weetman, David ORCID: https://orcid.org/0000-0002-5820-1388, Wilding, Craig, Steen, Keith ORCID: https://orcid.org/0000-0002-8933-8643, Morgan, John, Simard, Frederic and Donnelly, Martin ORCID: https://orcid.org/0000-0001-5218-1497 (2010) 'Association Mapping of Insecticide Resistance in Wild Anopheles gambiae Populations: Major Variants Identified in a Low-Linkage Disequilbrium Genome'. PLoS ONE, Vol 5, Issue 10, e13140.

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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
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance. QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0013140
Depositing User:	Users 183 not found.
Date Deposited:	18 Oct 2010 10:16
Last Modified:	16 Sep 2019 09:16
URI:	https://archive.lstmed.ac.uk/id/eprint/1668

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