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Epistasis--the essential role of gene interactions in the structure and evolution of genetic systems.

Patrick C. Phillips
- 01 Nov 2008 - 
- Vol. 9, Iss: 11, pp 855-867
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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.

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Journal ArticleDOI

Screen and Clean: a tool for identifying interactions in genome-wide association studies

TL;DR: A procedure called screen and clean (SC) for identifying liability loci, including interactions, by using the lasso procedure, which is a model selection tool for high‐dimensional regression, is proposed and explored.
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microRNAs in the Same Clusters Evolve to Coordinately Regulate Functionally Related Genes

TL;DR: It is suggested that positive Darwinian selection might be the driving force underlying the formation and evolution of miRNA clustering and the functional co-adaptation between new and old miRNAs in the miR-17–92 cluster.
Journal ArticleDOI

The Causes and Consequences of Genetic Interactions (Epistasis)

TL;DR: An overview of the current understanding of the mechanisms causing epistasis at the molecular level, the consequences of genetic interactions for evolution and genetic prediction, and the applications of epistasis for understanding biology and determining macromolecular structures is provided.

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Automated Design of Efficient and Functionally Diverse Enzyme Repertoires

TL;DR: FuncLib, an automated method for designing multipoint mutations at enzyme active sites using phylogenetic analysis and Rosetta design calculations, is described and opened the way to designing highly efficient and diverse catalytic repertoires.
References
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Journal ArticleDOI

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Paul Burton, +195 more
- 07 Jun 2007 - 
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

Ewan Birney, +320 more
- 14 Jun 2007 - 
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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