ArticlePLoS genetics2015
Transcriptional Derepression Uncovers Cryptic Higher-Order Genetic Interactions.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.Nature biotechnology · 2025Article
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Genome-scale analysis of interactions between genetic perturbations and natural variation.Nature communications · 2024Article
- Genome-scale analysis of interactions between genetic perturbations and natural variation.bioRxiv : the preprint server for biology · 2024Article
- Genetic basis of a spontaneous mutation's expressivity.Genetics · 2022Article
- The complex role of genetic background in shaping the effects of spontaneous and induced mutations.Yeast (Chichester, England) · 2021Review
- Decanalizing thinking on genetic canalization.Seminars in cell & developmental biology · 2019Review
- Article
- The complex underpinnings of genetic background effects.Nature communications · 2018Article
- Prevalence and patterns of higher-order drug interactions inNPJ systems biology and applications · 2018Article
- Mapping a diversity of genetic interactions in yeast.Current opinion in systems biology · 2017Article
- Genetic suppression: Extending our knowledge from lab experiments to natural populations.BioEssays : news and reviews in molecular, cellular and developmental biology · 2017Review
- Epistasis: Searching for Interacting Genetic Variants Using Crosses.G3 (Bethesda, Md.) · 2017Article
- Review
- Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.Genome biology and evolution · 2016Article
- Powerful decomposition of complex traits in a diploid model.Nature communications · 2016Article
- Modifiers of the Genotype-Phenotype Map: Hsp90 and Beyond.PLoS biology · 2016Review
- Article
- Gene-Environment Interactions in Stress Response Contribute Additively to a Genotype-Environment Interaction.PLoS genetics · 2016Article
- Diverse genetic architectures lead to the same cryptic phenotype in a yeast cross.Nature communications · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Disruption of certain genes can reveal cryptic genetic variants that do not typically show phenotypic effects. Because this phenomenon, which is referred to as 'phenotypic capacitance', is a potential source of trait variation and disease risk, it is important to understand how it arises at the genetic and molecular levels. Here, we use a cryptic colony morphology trait that segregates in a yeast cross to explore the mechanisms underlying phenotypic capacitance. We find that the colony trait is expressed when a mutation in IRA2, a negative regulator of the Ras pathway, co-occurs with specific combinations of cryptic variants in six genes. Four of these genes encode transcription factors that act downstream of the Ras pathway, indicating that the phenotype involves genetically complex changes in the transcriptional regulation of Ras targets. We provide evidence that the IRA2 mutation reveals the phenotypic effects of the cryptic variants by disrupting the transcriptional silencing of one or more genes that contribute to the trait. Supporting this role for the IRA2 mutation, deletion of SFL1, a repressor that acts downstream of the Ras pathway, also reveals the phenotype, largely due to the same cryptic variants that were detected in the IRA2 mutant cross. Our results illustrate how higher-order genetic interactions among mutations and cryptic variants can result in phenotypic capacitance in specific genetic backgrounds, and suggests these interactions might reflect genetically complex changes in gene expression that are usually suppressed by negative regulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.