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Here we explore to which degree the phenotypic manifestation of local and distant polymorphisms is a dynamic feature of regulatory design.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 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<\/jats:italic>\/trans<\/jats:italic> linkage patterns. However, when the shape of the cis-<\/jats:italic> 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.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our findings indicate that genetic variation affecting the form of cis<\/jats:italic>-regulatory input functions may reshape the genotype-phenotype map by changing the relative importance of cis<\/jats:italic> and trans<\/jats:italic> 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/1752-0509-1-32","type":"journal-article","created":{"date-parts":[[2007,7,25]],"date-time":"2007-07-25T18:13:43Z","timestamp":1185387223000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nonlinear regulation enhances the phenotypic expression of trans- acting genetic polymorphisms"],"prefix":"10.1186","volume":"1","author":[{"given":"Arne B","family":"Gjuvsland","sequence":"first","affiliation":[]},{"given":"Ben J","family":"Hayes","sequence":"additional","affiliation":[]},{"given":"Theo HE","family":"Meuwissen","sequence":"additional","affiliation":[]},{"given":"Erik","family":"Plahte","sequence":"additional","affiliation":[]},{"given":"Stig W","family":"Omholt","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2007,7,25]]},"reference":[{"key":"32_CR1","first-page":"3","volume":"Band IV","author":"G Mendel","year":"1865","unstructured":"Mendel G: Versuche \u00fcber Phlanzen-Hybriden. 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