How to perform meaningful estimates of genetic effects
2008 (English)In: PLoS Genetics, ISSN 1553-7390, Vol. 4, no 5, e1000062- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 4, no 5, e1000062- p.
IdentifiersURN: urn:nbn:se:uu:diva-149357DOI: 10.1371/journal.pgen.1000062ISI: 000256869100021PubMedID: 18451979OAI: oai:DiVA.org:uu-149357DiVA: diva2:404690