Epistasis Blog

From the Computational Genetics Laboratory at Dartmouth Medical School (www.epistasis.org)

Tuesday, June 19, 2012

From the Reaktionsnorm to the Adaptive Norm: The Norm of Reaction, 1909–1960

A great paper from 1999 on the history of reaction norms. A must read for anyone interested in gene-environment interaction.

Sarkar, S. From the Reaktionsnorm to the Adaptive Norm: The Norm of Reaction, 1909–1960. Biology and Philosophy 14: 235-252 (1999) [PDF]

Thursday, June 14, 2012

Dynamic epistasis for different alleles of the same gene

An interesting new paper documenting how epistasis may change depending on the alleles of a given gene.

Xu L, Barker B, Gu Z. Dynamic epistasis for different alleles of the same
gene. Proc Natl Acad Sci U S A. 2012 Jun 11. [PubMed]

Abstract

Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including pathway organization, evolution of sexual reproduction, mutational load, ploidy, genomic complexity, speciation, and the origin of life. Nevertheless, current understandings for the genome-wide distribution of epistasis are mostly inferred from interactions among one mutant type per gene, whereas how epistatic interaction partners change dynamically for different mutant alleles of the same gene is largely unknown. Here we address this issue by combining predictions from flux balance analysis and data from a recently published high-throughput experiment. Our results show that different alleles can epistatically interact with very different gene sets. Furthermore, between two random mutant alleles of the same gene, the chance for the allele with more severe mutational consequence to develop a higher percentage of negative epistasis than the other allele is 50∼70% in eukaryotic organisms, but only 20∼30% in bacteria and archaea. We developed a population genetics model that predicts that the observed distribution for the sign of epistasis can speed up the process of purging deleterious mutations in eukaryotic organisms. Our results indicate that epistasis among genes can be dynamically rewired at the genome level, and call on future efforts to revisit theories that can integrate epistatic dynamics among genes in biological systems.

Friday, June 01, 2012

The Challenges of Personalized Medicine and Genomics

This new piece in Science magazine summarizes nicely some of my concerns about the integration of whole genome sequencing into the clinic. I have tweeted about a number of these issues. A must read.

Liam R. Brunham, Michael R. Hayden. Whole-Genome Sequencing: The New Standard of Care? Science 336;1112-1113. [Science]

Rapid advances in DNA sequencing technology have made whole-genome sequencing (WGS) both technically and economically feasible. WGS has been used with great effect in specific settings to clarify molecular diagnosis and even to guide therapy. But are we ready for the routine use of WGS in the care of healthy individuals?