| 1. |
- Álvarez-Castro, José M., et al.
(författare)
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A unified model for functional and statistical epistasis and its application in quantitative trait loci analysis
- 2007
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 176:2, s. 1151-1167
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Tidskriftsartikel (refereegranskat)abstract
- Interaction between genes, or epistasis, is found to be common and it is a key, concept for understanding adaptation and evolution of natural populations, response to selection in breeding programs, and determination of complex disease. Current]),, two independent classes of models are used to study epistasis. Statistical models focus on maintaining desired statistical properties for detection and estimation of genetic effects and for the decomposition of genetic variance using average effects of allele Substitutions in populations as parameters. Functional models focus on the evolutionary consequences of the attributes of the genotype-phenotype map using natural effects of allele substitutions as parameters. Here we provide a new, general and unified model framework: the natural and orthogonal interactions (NOIA) model. NOIA implements tools for transforming genetic effects measured in One Population to the ones of other populations (e.g., between two experimental designs for QTL) and parameters of statistical and functional epistasis into each other (thus enabling us to obtain functional estimates of QTL), as demonstrated numerically. We develop graphical interpretations of functional and statistical models as regressions of the genotypic values on the gene content, which illustrates the difference between the models-the constraint on the slope of the functional regression-and when the models are equivalent. Furthermore, we use our theoretical foundations to conceptually clarify functional and statistical epistasis, discuss the advantages of NOIA over previous theory, and stress the importance of linking functional and statistical models.
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| 2. |
- Alvarez-Castro, Jose M., et al.
(författare)
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How to perform meaningful estimates of genetic effects
- 2008
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 4:5, s. e1000062-
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Le Rouzic, Arnaud, et al.
(författare)
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Dissection of the genetic architecture of body weight in chicken reveals the impact of epistasis on domestication traits
- 2008
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 179:3, s. 1591-1599
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Tidskriftsartikel (refereegranskat)abstract
- In this contribution, we study the genetic mechanisms leading to differences in the observed growth patterns of domesticated White Leghorn chickens and their wild ancestor the red jungle fowl. An epistatic QTL analysis for several body-weight measures from hatch to adulthood confirms earlier findings that polymorphisms at > , 15 loci contribute to body-weight determination in an F-2 intercross between these populations and that many loci are involved in complex genetic interactions. Here, we use a new genetic model to decompose the genetic effects of this multilocus epistatic genetic network. The results show how the functional modeling of genetic effects provides new insights into how genetic interactions in a large set of loci jointly contribute to phenotypic expression. By exploring the functional effects of QTL allels, we show that some alleles can display temporal shifts in the expression of genetic effects due to their dependencies on the genetic background. Our results demonstrate that the effects of many genes are dependent on genetic interactions with other loci and how their involvement in the domestication process relies on these interactions.
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