ArticleBMC systems biology2007
Nonlinear regulation enhances the phenotypic expression of trans-acting genetic polymorphisms.
Article in BMC systems biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- The integrative biology of genetic dominance.Biological reviews of the Cambridge Philosophical Society · 2021Review
- Genetic variation in the Yolk protein expression network of Drosophila melanogaster: sex-biased negative correlations with longevity.Heredity · 2012Article
- Genotype-Phenotype Map Characteristics of an In silico Heart Cell.Frontiers in physiology · 2011Article
- Phenomics: the next challenge.Nature reviews. Genetics · 2010Review
- Article
- A framework for evolutionary systems biology.BMC systems biology · 2009Article
- Complex genetics control natural variation in Arabidopsis thaliana resistance to Botrytis cinerea.Genetics · 2008Article
- Using genetic markers to orient the edges in quantitative trait networks: the NEO software.BMC systems biology · 2008Article
- Borges dilemma, fundamental laws, and systems biology.Bioinformatics and biology insights · 2008Article
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5 authors.
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Abstract
backgroundGenetic variation explains a considerable part of observed phenotypic variation in gene expression networks. This variation has been shown to be located both locally (cis) and distally (trans) to the genes being measured. Here we explore to which degree the phenotypic manifestation of local and distant polymorphisms is a dynamic feature of regulatory design.
resultsBy combining mathematical models of gene expression networks with genetic maps and linkage analysis we find that very different network structures and regulatory motifs give similar cis/trans linkage patterns. However, when the shape of the cis-regulatory input functions is more nonlinear or threshold-like, we observe for all networks a dramatic increase in the phenotypic expression of distant compared to local polymorphisms under otherwise equal conditions.
conclusionOur findings indicate that genetic variation affecting the form of cis-regulatory input functions may reshape the genotype-phenotype map by changing the relative importance of cis and trans variation. Our approach combining nonlinear dynamic models with statistical genetics opens up for a systematic investigation of how functional genetic variation is translated into phenotypic variation under various systemic conditions.
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