April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
A System Genetics Approach to Define a Genetic Network Regulating Gap43 and Pten
Author Affiliations & Notes
  • Natalie E. Freeman-Anderson
    Ophthalmology, UTHSC: Hamilton Eye Institute, Memphis, Tennessee
  • Clint W. Abner
    Ophthalmology, UTHSC: Hamilton Eye Institute, Memphis, Tennessee
  • Lu Lu
    Department of Anatomy and Neurobiology and Center for Integrative and Translational Genomics, UTHSC, Memphis, Tennessee
  • Robert W. Williams
    Department of Anatomy and Neurobiology and Center for Integrative and Translational Genomics, UTHSC, Memphis, Tennessee
  • William E. Orr
    Ophthalmology, UTHSC: Hamilton Eye Institute, Memphis, Tennessee
  • Justin P. Templeton
    Ophthalmology, UTHSC: Hamilton Eye Institute, Memphis, Tennessee
  • Eldon E. Geisert
    Ophthalmology, UTHSC: Hamilton Eye Institute, Memphis, Tennessee
  • Footnotes
    Commercial Relationships  Natalie E. Freeman-Anderson, None; Clint W. Abner, None; Lu Lu, None; Robert W. Williams, None; William E. Orr, None; Justin P. Templeton, None; Eldon E. Geisert, None
  • Footnotes
    Support  NIH Grant EY017841, NEI Core Grant P30EY013080, Unrestricted Grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3311. doi:
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      Natalie E. Freeman-Anderson, Clint W. Abner, Lu Lu, Robert W. Williams, William E. Orr, Justin P. Templeton, Eldon E. Geisert; A System Genetics Approach to Define a Genetic Network Regulating Gap43 and Pten. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3311.

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Abstract

Purpose: : To define the genetic network modulating the expression of Gap43 and Pten in the retina using the Hamilton Eye Institute Retinal Database and the bioinformatic tools available on GeneNetwork.

Methods: : The Hamilton Eye Institute Retinal Database contains the data analysis of 346 Illumina Sentrix BeadChip Arrays (Mouse WG-6v2). Eighty strains of mice are presented including 75 BXD RI strains, the parental strains (C57Bl/6J and DBA/2J), the reciprocal crosses, and the BALB/c mice. Independent biological samples for at least two animals from each sex were obtained. Animals were sacrificed by cervical dislocation, the retinas were immediately removed, and preserved. Total RNA was prepared followed by the production of biotinylated cRNAs, which were pipetted into the Mouse WG-6V2 arrays. All samples were inspected for internal quality and the raw image data was assessed via Illumina BeadStudio software and MIAME standards. The data was globally normalized with rank invariant 2z + 8 stabilization.

Results: : The Hamilton Eye Institute Retinal Database complements and extends our previous whole eye transcriptome resource that is located on the GeneNetwork website (www.genenetwork.org, Hamilton Eye Institute Mouse Eye Database). The Hamilton Eye Institute Retinal Database resource was used to extract unique transcriptome signatures for specific cell types in the retina. The bioinformatic tools located within GeneNetwork in conjunction with the Hamilton Eye Institute Retinal Database were used to provide an example of a retinal network that is believed to be associated with axonal growth. The network involves high correlations of beta loop helix beta transcription factors (Sox2 and Pax6), a neuron specific transcription factor for neuronal development (NeuroD1), genes involved in axonal growth (Gap43 and Pten), genes involved in DNA binding (Pcna and Zbed4), and an inhibitor of DNA binding (ID2).

Conclusions: : The Hamilton Eye Institute Retinal Database provides a wealth of research possibilities including; defining the molecular signatures within the retina, ascertaining the unique cell signatures for a specific cell type, identifying candidate genes for human disease, ability to understand genetic networks regulating tissue specific gene expression, and identifying the complex interactions of the genomic loci that underlie the complex structures of the retina.

Keywords: retina • gene microarray • gene/expression 
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