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Mol Biol Evol. 2019 Aug 10. pii: msz183. doi: 10.1093/molbev/msz183. [Epub ahead of print]

Optimizing the power to identify the genetic basis of complex traits with Evolve and Resequence studies.

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Institute für Populationsgenetik, Vetmeduni Vienna, Veterinärplatz 1, 1210 Wien, Austria.
Vienna Graduate School of Population Genetics.


Evolve and Resequence (E&R) studies are frequently used to dissect the genetic basis of quantitative traits. By subjecting a population to truncating selection for several generations and estimating the allele frequency differences between selected and non-selected populations using Next Generation Sequencing, the loci contributing to the selected trait may be identified. The role of different parameters, such as, the population size or the number of replicate populations have been examined in previous works. However, the influence of the selection regime, i.e. the strength of truncating selection during the experiment, remains little explored. Using whole genome, individual based forward simulations of E&R studies, we found that the power to identify the causative alleles may be maximized by gradually increasing the strength of truncating selection during the experiment. Notably, such an optimal selection regime comes at no or little additional cost in terms of sequencing effort and experimental time. Interestingly, we also found that a selection regime which optimizes the power to identify the causative loci is not necessarily identical to a regime that maximizes the phenotypic response. Finally, our simulations suggest that an E&R study with an optimized selection regime may have a higher power to identify the genetic basis of quantitative traits than a GWAS, highlighting that E&R is a powerful approach for finding the loci underlying complex traits. E&R studies are however more risky than GWAS as suboptimal selection regimes lead to a weak performance.


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