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Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene

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Systems Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1488))

Abstract

Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas. We found that chromosome 1 harbors an eQTL that modulates the expression of Sncg in the mouse retina and identified Pfdn2 as the candidate upstream modulator of Sncg expression. Downregulation of Pfdn2 in enriched RGCs causes a concomitant reduction in Sncg. In this chapter, we describe our strategy and methods for identifying and confirming a genetic modulation of a glaucoma-associated gene. A similar method can be applied to other genes expressed in other tissues.

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Acknowledgments

We would like to thank Dr. Robert Williams (UTHSC) and Dr. Vanessa Morales-Tirado (UTHSC) for contributing to the research design and execution of our original study that is published in The FEBS Journal. We would like to thank Dr. Dan Rosson (UTHSC) for technical assistance with the cell sorting. We thank Dr. Michael Whitt (UTHSC), Dr. Tony Reiner (UTHSC), and Dr. R.K. Rao (UTHSC) for providing C57BL/6J mice eyes. We also thank Dr. Lu Lu (UTHSC) for his assistance in generating the BXD microarray datasets that were used in these analyses. We also thank Dr. Eldon Geisert (Emory University) and Mr. Bill Orr (UTHSC) for formatting the dataset of Howell et al. (NCBI accession number GSE26299) so that it could be mined within GeneNetwork. Funding provided by Juvenile Diabetes Research Foundation Grant (VMT), Research to Prevent Blindness Award (PI: James C. Fleming), National Eye Institute Vision Core Grant (PI: Dianna Johnson), National Eye Institute EY021200 (MMJ).

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Authors and Affiliations

  1. Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health Science Center, 930 Madison Ave., Suite 710, Memphis, TN, 38163, USA

    Monica M. Jablonski

  2. Department of Anatomy and Neurobiology, Hamilton Eye Institute, The University of Tennessee Health Science Center, 930 Madison Ave., Suite 710, Memphis, TN, 38163, USA

    Sumana R. Chintalapudi & Monica M. Jablonski

  3. Department of Pharmaceutical Sciences, Hamilton Eye Institute, The University of Tennessee Health Science Center, 930 Madison Ave., Suite 710, Memphis, TN, 38163, USA

    Monica M. Jablonski

Authors
  1. Sumana R. Chintalapudi
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  2. Monica M. Jablonski
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Corresponding author

Correspondence to Monica M. Jablonski .

Editor information

Editors and Affiliations

  1. Department of Infection Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig, Niedersachsen, Germany

    Klaus Schughart

  2. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA

    Robert W. Williams

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Chintalapudi, S.R., Jablonski, M.M. (2017). Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene. In: Schughart, K., Williams, R. (eds) Systems Genetics. Methods in Molecular Biology, vol 1488. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6427-7_18

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  • DOI: https://doi.org/10.1007/978-1-4939-6427-7_18

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6425-3

  • Online ISBN: 978-1-4939-6427-7

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