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Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA.
Gene expression QTL (eQTL) mapping can suggest candidate regulatory relationships between genes. Recent advances in mammalian phenotype annotation such as mammalian phenotype ontology (MPO) enable systematic analysis of the phenotypic spectrum subserved by many genes. In this study we combined eQTL mapping and phenotypic spectrum analysis to predict gene regulatory relationships. Five pairs of genes with similar phenotypic effects and potential regulatory relationships suggested by eQTL mapping were identified. Lines of evidence supporting some of the predicted regulatory relationships were obtained from biological literature. A particularly notable example is that promoter sequence analysis and real-time PCR assays support the predicted regulation of protein kinase C epsilon (Prkce) by cAMP responsive element binding protein 1 (Creb1). Our results show that the combination of gene eQTL mapping and phenotypic spectrum analysis may provide a valuable approach to uncovering gene regulatory relations underlying mammalian phenotypes.
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