Diversity, Differentiation, and Linkage Disequilibrium: Prospects for Association Mapping in the Malaria VectorAnopheles arabiensis

Abstract

Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples can result in spurious associations if not accounted for. As such, it is useful to have a detailed understanding of these factors before conducting association mapping experiments. Here we conducted whole-genome sequencing on 24 specimens of the malaria mosquito vector, Anopheles arabiensis, to further understanding of patterns of genetic diversity, population subdivision and linkage disequilibrium in this species. We found high levels of genetic diversity within the An. arabiensis genome, with ~800,000 high-confidence, single- nucleotide polymorphisms detected. However, levels of nucleotide diversity varied significantly both within and between chromosomes. We observed lower diversity on the X chromosome, within some inversions, and near centromeres. Population structure was absent at the local scale (Kilombero Valley, Tanzania) but detected between distant populations (Cameroon vs. Tanzania) where differentiation was largely restricted to certain autosomal chromosomal inversions such as 2Rb. Overall, linkage disequilibrium within An. arabiensis decayed very rapidly (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium was observed within some inversions, suggesting that recombination is reduced in those regions. The overall low levels of linkage disequilibrium suggests that association studies in this taxon will be very challenging for all but variants of large effect, and will require large sample sizes.

Whole‐genome resequencing of extreme phenotypes in collared flycatchers highlights the difficulty of detecting quantitative trait loci in natural populations

“…) and the mosquito Anopheles arabiensis (Marsden et al . ). Rapid decay of LD with increasing chromosomal distance means that QTL are more difficult to detect via association analyses of linked SNPs.…”

“…However, LD decays much more rapidly in the collared flycatcher (Kawakami et al 2014a) (Fig. 1), and invertebrates such as the nematode Caenorhabditis remanei (Cutter et al 2006), the fruit fly Drosophila melanogaster (Mackay et al 2012) and the mosquito Anopheles arabiensis (Marsden et al 2014). Rapid decay of LD with increasing chromosomal distance means that QTL are more difficult to detect via association analyses of linked SNPs.…”

Impact of ENSO 2016–17 on regional climate and malaria vector dynamics in Tanzania

“…gambiae s.l. tested here and in other concurrent studies in the area (Govella et al 2009, Marsden et al 2014, Maliti et al 2015, Kaindoa et al 2017a, all An. gambiae s.l.…”

The genetic basis of host choice and resting behavior in the major African malaria vector,Anopheles arabiensis

“…100-1000) are needed to get a quantitative estimate of the SNP heritability of host preference and potentially uncover important candidate genes. However, low LD across the genome of this species may limit the outcome of this approach to large-effect mutations (Marsden et al 2014). Larger sample sizes may also uncover a genetic component to resting behavior, which we did not detect here but cannot rule out.…”

“…Previous tests for population structure only revealed differentiation between distant villages (Marsden et al 2014). Thus, by comparing individual genomes representing host preference phenotypes (and resting behavior) from within the same village (Lupiro), we limited the identification of demographic SNPs in our data set.…”