Genetic architecture of a mutation's expressivity and penetrance

BioRxiv : the Preprint Server for Biology
Rachel SchellIan M Ehrenreich


Mutations often have different effects in genetically distinct individuals. Epistasis between mutations and segregating loci is known to be a major contributor to these background effects, but the architecture of these genetic interactions remains largely unknown. Here, we characterize how segregating loci in a cross of two Saccharomyces cerevisiae strains impact growth following the deletion of the histone deacetylase HOS3. The functions of HOS3 are not well understood and historically its deletion has shown little effect on reference strains. However, we map two loci that genetically interact with HOS3 and each other to produce a broad range of responses to the deletion, including near inviability. Although these interactions explain nearly all of the deletion's expressivity, their penetrance depends on a liability threshold involving at least 11 additional nuclear and mitochondrial loci. Multiple lines of evidence imply the deletion uncovers genetically complex changes in translation and genome stability in the mitochondria, suggesting a novel connection between Hos3-mediated deacetylation and the mitochondria. These results provide a valuable example of the complicated and unexpected mechanisms that can cause background eff...Continue Reading

Related Concepts

Chromosomes, Human
DNA Resequencing
Standing Position
Anemia, Sickle Cell
Genome Sequencing
Whole Genome Sequencing

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