Epistasis--the essential role of gene interactions in the structure and evolution of genetic systems.
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TLDR
There is a renewed appreciation both for the importance of studying gene interactions and for addressing these questions in a unified, quantitative manner with the advent of high-throughput functional genomics.Abstract:
Epistasis, or interactions between genes, has long been recognized as fundamentally important to understanding the structure and function of genetic pathways and the evolutionary dynamics of complex genetic systems. With the advent of high-throughput functional genomics and the emergence of systems approaches to biology, as well as a new-found ability to pursue the genetic basis of evolution down to specific molecular changes, there is a renewed appreciation both for the importance of studying gene interactions and for addressing these questions in a unified, quantitative manner.read more
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Posted ContentDOI
Coordinated Interaction: A model and test for globally signed epistasis in complex traits
Brooke Sheppard,Nadav Rappoport,Nadav Rappoport,Po-Ru Loh,Po-Ru Loh,Stephen Sanders,Dahl A,Dahl A,Noah Zaitlen,Noah Zaitlen +9 more
TL;DR: A model for structured polygenic epistasis, called Coordinated Interaction (CI), is developed and it is proved that several recent theories of genetic architecture fall under the formal umbrella of CI, a new dimension of Genetic architecture that can capture structured, systemic interactions in complex human traits.
Journal ArticleDOI
Learning Epistasis and Residue Coevolution Patterns: Current Trends and Future Perspectives for Advancing Enzyme Engineering
TL;DR: In this paper , the authors outline a complete theoretical journey through the processes of protein engineering methods such as directed evolution and rational design and reflect on these strategies and data-driven hybrid strategies in the context of sequence space.
Posted Content
Critical properties of complex fitness landscapes
TL;DR: The authors studied the global and local structure of complex fitness landscapes of interacting loci that describe protein folds or sets of interacting genes forming pathways or modules, and found that high peaks are more likely to be found near other high peaks, corroborating Kauffman's "Massif Central" hypothesis.
Posted ContentDOI
Back to the future: Implications of genetic complexity for hybrid breeding strategies
TL;DR: Simulations based on the NK model of genetic architecture found that constraining genetic space and reducing effective population size, through program decentralization and disproportionate inbred use, is required to expose additive genetic variation and thus facilitate heritable genetic gains.
Book ChapterDOI
Getting to Know Viral Evolutionary Strategies: Towards the Next Generation of Quasispecies Models.
Susanna C. Manrubia,Ester Lázaro +1 more
TL;DR: This work aims to be witnesses of an integration of still decoupled approaches, leading into more accurate and realistic quasispecies models able to capture robust generalities and endowed with a satisfactory predictive power.
References
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TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Book
The Origins of Order: Self-Organization and Selection in Evolution
TL;DR: The structure of rugged fitness landscapes and the structure of adaptive landscapes underlying protein evolution, and the architecture of genetic regulatory circuits and its evolution.
Journal ArticleDOI
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
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TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
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