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Author (up) Gjuvsland, AB; Hayes, BJ; Meuwissen, TH; Plahte, E; Omholt, SW doi  openurl
  Title Nonlinear regulation enhances the phenotypic expression of trans-acting genetic polymorphisms Type Journal Article
  Year 2007 Publication BMC Systems Biology Abbrev Journal BMC Syst Biol  
  Volume 1 Issue 1 Pages 32  
  Corporate Author Thesis  
  Address  
  Keywords  
  Abstract ABSTRACT: BACKGROUND: Genetic 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. RESULTS: By 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. CONCLUSIONS: Our 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.  
  Publisher Place Editor  
  Language ENG Summary Language Orig Title  
  Series Editor Series Title Abbrev Series Title  
  Series Volume Series Issue Edition  
  Issn 1752-0509 Isbn Medium  
  Area Expedition Conference  
  Notes PUBMED: 17651484 Approved no  
  Location Arne Gjuvsland (arne.gjuvsland@umb.no)  
  Call Number Cigene @ arne.gjuvsland @ Serial 983  
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