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Integrated gene expression profiling and linkage analysis in the rat

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Abstract

The combined application of genome-wide expression profiling from microarray experiments with genetic linkage analysis enables the mapping of expression quantitative trait loci (eQTLs) which are primary control points for gene expression across the genome. This approach allows for the dissection of primary and secondary genetic determinants of gene expression. The cis-acting eQTLs in practice are easier to investigate than the trans-regulated eQTLs because they are under simpler genetic control and are likely to be due to sequence variants within the gene itself or its neighboring regulatory elements. These genes are therefore candidates both for variation in gene expression and for contributions to whole-body phenotypes, particularly when these are located within known and relevant physiologic QTLs. Multiple trans-acting eQTLs tend to cluster to the same genetic location, implying shared regulatory control mechanisms that may be amenable to network analysis to identify gene clusters within the same metabolic pathway. Such clusters may ultimately underlie development of individual complex, whole-body phenotypes. The combined expression and linkage approach has been applied successfully in several mammalian species, including the rat which has specific features that demonstrate its value as a model for studying complex traits.

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Acknowledgments

The authors acknowledge funding to TJA from the MRC Clinical Sciences Centre, from the British Heart Foundation, and from a Wellcome Trust Cardiovascular Functional Genomics initiative; to MP and TJA from the Wellcome Trust Collaborative Research Initiative Grant; and founding from a European Union FP6 Integrated Project for rat functional genomics. MP is an international research scholar of the Howard Hughes Medical Institute and was supported by grant 1M6837805002 from the Ministry of Education of the Czech Republic.

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Authors and Affiliations

  1. MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, W12 0NN, United Kingdom

    Enrico Petretto, Jonathan Mangion & Timothy J. Aitman

  2. Institute of Physiology, Czech Academy of Sciences and Centre for Applied Genomics, 142 20, Prague 4, Czech Republic

    Michal Pravanec

  3. Institute of Biology and Medical Genetics, Charles University, 120 00, Prague 2, Czech Republic

    Michal Pravanec

  4. Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, 13125, Germany

    Norbert Hubner

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  1. Enrico Petretto
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  2. Jonathan Mangion
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  3. Michal Pravanec
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  5. Timothy J. Aitman
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Correspondence to Timothy J. Aitman.

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Petretto, E., Mangion, J., Pravanec, M. et al. Integrated gene expression profiling and linkage analysis in the rat. Mamm Genome 17, 480–489 (2006). https://doi.org/10.1007/s00335-005-0181-1

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