Mapping and dissecting capacitating epistasis in a population subjected to long-term, directional selection

• Dissection of the genetic mechanisms that constitute quantitative traits is challenging, especially when the underlying biology is complex, and dependent on the interaction of multiple genes and environmental factors. Unexplained phenotypic variance or missing heritability in studies of quantitative traits has often been explained by a high polygenicity of the trait, i.e. many small effect loci, as well as epistasis. The ability to detect both phenomenons has so far been limited by the significantly increased power and resolution required, with studies often failing to explain a majority of the heritability or phenotypic variance of the trait investigated.  Here, we use low-coverage, whole-genome sequencing data of a large (n>3300), 18-generation advanced intercross line formed from generation 41 of the Virginia body weight lines, which originated from an outbred common stock of chickens and are bi-directionally selected for 8-week body weight. this study attempts to use this large and powerful population to explore the role of capacitating epistasis in the long-term selection responses in the Virginia chicken lines. Using a mix of stratification and vQTL analysis, we Identify 6 potential capacitor hubs of varying strength, which together capacitate an effect of 259g. Furthermore, the higher resolution enabled a dissection of a previously identified epistatic interaction between QTL on chromosome 4 and 7 into a network where two capacitors on Chromosome 4 and 7 release an effect for two capacitated loci on chromosome 4, explaining more than twice the effect of the purely additive model when accounting for the interaction ( 136.9g vs 331.5g). This provides not only a better estimate for how genetic components correspond to the selection response observed,  but also a mechanistic example of how higher resolution and power enabled the dissection of previously large, additive QTL into a complex network of multiple smaller, interacting QTL, coherent with previous assumptions about the polygenicity and complexity of a highly polygenic trait.

Ämnesord

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

Nyckelord

Quantitative Genetics

Avian genetics

QTL mapping

Epistasis

Chicken genetics

Biologi med inriktning mot populationsbiologi

Biology with specialization in Population Biology

Bioinformatik

Bioinformatics

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