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Combining gene expression QTL mapping and phenotypic spectrum analysis to uncover gene regulatory relationships

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Abstract

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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Notes

  1. The relation between log of odds (LOD) and the likelihood ratio statistic (LRS) is: LOD = LRS/4.61.2.

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Acknowledgments

The authors thank the reviewers for helpful suggestions. This work was supported by a PhRMA Foundation grant (YC); NIH grants HD52472 (DG), AA14425 (LL), AA13499 (RWW), and CA73753 (LMP); and by funds from the Muirhead Chair Endowment at the University of Tennessee Health Science Center (LMP).

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Authors and Affiliations

  1. Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Lei Bao, Hongqiang Li, Mi Zhou & Yan Cui

  2. Center of Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Lei Bao, Jeremy L. Peirce, Ramin Homayouni, Hongqiang Li, Mi Zhou, Lu Lu, Robert W. Williams, Dan Goldowitz & Yan Cui

  3. Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Lai Wei & Lawrence M. Pfeffer

  4. Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Lai Wei, Jeremy L. Peirce, Ramin Homayouni, Lu Lu, Robert W. Williams & Dan Goldowitz

  5. Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Hao Chen

  6. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, 38163, USA

    Robert W. Williams

  7. Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN, 38163, USA

    Yan Cui

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  1. Lei Bao
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Correspondence to Yan Cui.

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Bao, L., Wei, L., Peirce, J.L. et al. Combining gene expression QTL mapping and phenotypic spectrum analysis to uncover gene regulatory relationships. Mamm Genome 17, 575–583 (2006). https://doi.org/10.1007/s00335-005-0172-2

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