Systems genetics analysis to identify the genetic modulation of a glaucoma-associated gene

Sumana R. Chintalapudi, Monica Jablonski

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages391-417
Number of pages27
DOIs
StatePublished - Jan 1 2017

Publication series

NameMethods in Molecular Biology
Volume1488
ISSN (Print)1064-3745

Fingerprint

Retinal Ganglion Cells
Glaucoma
Genes
Retina
Down-Regulation
Synucleins
Gene Expression
Retinal Diseases
Chromosomes, Human, Pair 1
Carisoprodol
Neurodegenerative Diseases
Axons

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

Cite this

Chintalapudi, S. R., & Jablonski, M. (2017). Systems genetics analysis to identify the genetic modulation of a glaucoma-associated gene. In Methods in Molecular Biology (pp. 391-417). (Methods in Molecular Biology; Vol. 1488). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-6427-7_18

Systems genetics analysis to identify the genetic modulation of a glaucoma-associated gene. / Chintalapudi, Sumana R.; Jablonski, Monica.

Methods in Molecular Biology. Humana Press Inc., 2017. p. 391-417 (Methods in Molecular Biology; Vol. 1488).

Research output: Chapter in Book/Report/Conference proceedingChapter

Chintalapudi, SR & Jablonski, M 2017, Systems genetics analysis to identify the genetic modulation of a glaucoma-associated gene. in Methods in Molecular Biology. Methods in Molecular Biology, vol. 1488, Humana Press Inc., pp. 391-417. https://doi.org/10.1007/978-1-4939-6427-7_18
Chintalapudi SR, Jablonski M. Systems genetics analysis to identify the genetic modulation of a glaucoma-associated gene. In Methods in Molecular Biology. Humana Press Inc. 2017. p. 391-417. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-6427-7_18
Chintalapudi, Sumana R. ; Jablonski, Monica. / Systems genetics analysis to identify the genetic modulation of a glaucoma-associated gene. Methods in Molecular Biology. Humana Press Inc., 2017. pp. 391-417 (Methods in Molecular Biology).
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