How to perform meaningful estimates of genetic effects

Although the genotype-phenotype map plays a central role both in Quantitative and Evolutionary Genetics, the formalization of a completely general and satisfactory model of genetic effects, particularly accounting for epistasis, remains a theoretical challenge. Here, we use a two-locus genetic system in simulated populations with epistasis to show the convenience of using a recently developed model, NOIA, to perform estimates of genetic effects and the decomposition of the genetic variance that are orthogonal even under deviations from the Hardy-Weinberg proportions. We develop the theory for how to use this model in interval mapping of quantitative trait loci using Halley-Knott regressions, and we analyze a real data set to illustrate the advantage of using this approach in practice. In this example, we show that departures from the Hardy-Weinberg proportions that are expected by sampling alone substantially alter the orthogonal estimates of genetic effects when other statistical models, like F-2 or G2A, are used instead of NOIA. Finally, for the first time from real data, we provide estimates of functional genetic effects as sets of effects of natural allele substitutions in a particular genotype, which enriches the debate on the interpretation of genetic effects as implemented both in functional and in statistical models. We also discuss further implementations leading to a completely general genotype-phenotype map.

Le Rouzic, ArnaudUppsala universitet,Centrum för bioinformatik (author)
Carlborg, ÖrjanUppsala universitet,Centrum för bioinformatik(Swepub:uu)orcar991 (author)
Uppsala universitetCentrum för bioinformatik (creator_code:org_t)

In:PLoS Genetics: Public Library of Science (PLoS)4:5, s. e1000062-1553-73901553-7404

By the author/editor: Alvarez-Castro, ...; Le Rouzic, Arnau ...; Carlborg, Örjan

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