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Genetic divergence and the genetic architecture of complex traits in chromosome substitution strains of mice

Genetic divergence and the genetic architecture of complex traits in chromosome substitution strains of mice

Bmc Genetics 13(): 38-38

The genetic architecture of complex traits strongly influences the consequences of inheritedmutations, genetic engineering, environmental and genetic perturbations, and natural andartificial selection. But because most studies are under-powered, the picture of complex traitsis often incomplete. Chromosome substitution strains (CSSs) are a unique paradigm for thesegenome surveys because they enable statistically independent, powerful tests for thephenotypic effects of each chromosome on a uniform inbred genetic background. A previousCSS survey in mice and rats revealed many complex trait genes (QTLs), large phenotypiceffects, extensive epistasis, as well as systems properties such as strongly directionalphenotypic changes and genetically-determined limits on the range of phenotypic variation.However, the unusually close genetic relation between the CSS progenitor strains in thatstudy raised questions about the impact of genetic divergence: would greater divergencebetween progenitor strains, with the corresponding changes in gene regulation and proteinfunction, lead to significantly more distinctive phenotypic features, or alternatively wouldepistasis and systems constraints, which are pervasive in CSSs, limit the range of phenotypicvariation regardless of the extent of DNA sequence variation? We analyzed results for an extensive survey of traits in two new panels of CSSs where thedonor strains were derived from inbred strains with more distant origins and discovered astrong similarity in genetic and systems properties among the three CSS panels, regardless ofdivergence time.Our results argue that DNA sequence differences between host and donor strains did notsubstantially affect the architecture of complex traits, and suggest instead that strong epistasisbuffered the phenotypic effects of genetic divergence, thereby constraining the range ofphenotypic variation.

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Accession: 053381661

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PMID: 22606935

DOI: 10.1186/1471-2156-13-38

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