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Genetic networks in the mouse retina: growth associated protein 43 and phosphatase tensin homolog network.

Freeman NE, Templeton JP, Orr WE, Lu L, Williams RW, Geisert EE - Mol. Vis. (2011)

Bottom Line: For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten).Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database.The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Center for Vision Research, Memphis, TN, USA.

ABSTRACT

Purpose: The present study examines the structure and covariance of endogenous variation in gene expression across the recently expanded family of C57BL/6J (B) X DBA/2J (D) Recombinant Inbred (BXD RI) strains of mice. This work is accompanied by a highly interactive database that can be used to generate and test specific hypotheses. For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten).

Methods: The Hamilton Eye Institute (HEI) Retina Database within GeneNetwork features the data analysis of 346 Illumina Sentrix BeadChip Arrays (mouse whole genome-6 version 2). 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/cByJ mice. Independent biologic samples for at least two animals from each gender were obtained with a narrow age range (48 to 118 days). Total RNA was prepared followed by the production of biotinylated cRNAs, which were pipetted into the Mouse WG-6V2 arrays. The data was globally normalized with rank invariant and stabilization (2z+8).

Results: The HEI Retina Database is located on the GeneNetwork website. The database was used to extract unique transcriptome signatures for specific cell types in the retina (retinal pigment epithelial, amacrine, and retinal ganglion cells). Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database. Bioinformatic tools located within GeneNetwork in conjunction with the HEI Retina Database were used to identify the unique signature Quantitative Trait Loci (QTLs) for Gap43 and Pten on chromosomes 1, 2, 12, 15, 16, and 19. Gap43 and Pten possess networks that are similar to ganglion cell networks that may be associated with axonal growth in the mouse retina. This network involves high correlations of transcription factors (SRY sex determining region Y-box 2 [Sox2], paired box gene 6 [Pax6], and neurogenic differentiation 1 [Neurod1]), and genes involved in DNA binding (proliferating cell nuclear antigen [Pcna] and zinc finger, BED-type containing 4 [Zbed4]), as well as an inhibitor of DNA binding (inhibitor of DNA binding 2, dominant negative helix-loop-helix protein [Id2]). Furthermore, we identified the potential upstream modifiers on chromosome 2 (teashirt zinc finger homeobox 2 [Tshz2], RNA export 1 homolog [Rae1] and basic helix-loop-helix domain contatining, class B4 [Bhlhb4]) on chromosome 15 (RAB, member of RAS oncogene family-like 2a [Rabl2a], phosphomannomutase 1 [Pmm1], copine VIII [Cpne8], and fibulin 1 [Fbln1]).

Conclusions: The endogenous variation in mRNA levels among BXD RI strains can be used to explore and test expression networks underlying variation in retina structure, function, and disease susceptibility. The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.

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Related in: MedlinePlus

A network graph representing the growth associated protein43/ phosphatase tensin homolog (Gap43/Pten) network and the potential components for upstream modulation of the Gap43/Pten network. This network graph produces a relational Gap43/Pten network shown in blue. The colored lines represent the direct correlative relationship and the strength of the correlation is −1.0 to 1.0. The genes denoted in red: Basic helix loop helix beta4 (Bhlhb4), teashirt zinc finger homeobox 2 (Tshz2), and RNA export protein1 homolog (Rae1) are candidates from chromosome 2, cis-acting QTLs between 169 Mb and 182 Mb. The genes illustrated in green are the candidate genes located on chromosome 15 between 82 Mb and 92 Mb; phosphomannomutase1 (Pmm1), copine VIII (Cpne8), RAB, member of RAS oncogene family-like 2A (Rabl2a), and fibulin 1 (Fbln1).
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f5: A network graph representing the growth associated protein43/ phosphatase tensin homolog (Gap43/Pten) network and the potential components for upstream modulation of the Gap43/Pten network. This network graph produces a relational Gap43/Pten network shown in blue. The colored lines represent the direct correlative relationship and the strength of the correlation is −1.0 to 1.0. The genes denoted in red: Basic helix loop helix beta4 (Bhlhb4), teashirt zinc finger homeobox 2 (Tshz2), and RNA export protein1 homolog (Rae1) are candidates from chromosome 2, cis-acting QTLs between 169 Mb and 182 Mb. The genes illustrated in green are the candidate genes located on chromosome 15 between 82 Mb and 92 Mb; phosphomannomutase1 (Pmm1), copine VIII (Cpne8), RAB, member of RAS oncogene family-like 2A (Rabl2a), and fibulin 1 (Fbln1).

Mentions: A correlative network graph and correlation matrices are additional ways to view this group of genes that form the core of the Gap43/Pten network. Using the tools available within GeneNetwork, a network graph was computed for the Gap43/Pten network. The eight genes form the core of the Gap43/Pten network (light blue) are shown in Figure 5. All of these genes possess expression levels that highly correlate across the BXD RI strains (r=0.5–1.0). The correlations between each of these genes are color coded in the network graph illustrated in Figure 5 and presented in Table 2. We find that the average range of correlation is between 0.54 and 0.95. The lowest correlation is between Id2 and Zbed4, with a value of 0.54, while the highest correlation (0.95) exists between Sox2 and Pax6.


Genetic networks in the mouse retina: growth associated protein 43 and phosphatase tensin homolog network.

Freeman NE, Templeton JP, Orr WE, Lu L, Williams RW, Geisert EE - Mol. Vis. (2011)

A network graph representing the growth associated protein43/ phosphatase tensin homolog (Gap43/Pten) network and the potential components for upstream modulation of the Gap43/Pten network. This network graph produces a relational Gap43/Pten network shown in blue. The colored lines represent the direct correlative relationship and the strength of the correlation is −1.0 to 1.0. The genes denoted in red: Basic helix loop helix beta4 (Bhlhb4), teashirt zinc finger homeobox 2 (Tshz2), and RNA export protein1 homolog (Rae1) are candidates from chromosome 2, cis-acting QTLs between 169 Mb and 182 Mb. The genes illustrated in green are the candidate genes located on chromosome 15 between 82 Mb and 92 Mb; phosphomannomutase1 (Pmm1), copine VIII (Cpne8), RAB, member of RAS oncogene family-like 2A (Rabl2a), and fibulin 1 (Fbln1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108897&req=5

f5: A network graph representing the growth associated protein43/ phosphatase tensin homolog (Gap43/Pten) network and the potential components for upstream modulation of the Gap43/Pten network. This network graph produces a relational Gap43/Pten network shown in blue. The colored lines represent the direct correlative relationship and the strength of the correlation is −1.0 to 1.0. The genes denoted in red: Basic helix loop helix beta4 (Bhlhb4), teashirt zinc finger homeobox 2 (Tshz2), and RNA export protein1 homolog (Rae1) are candidates from chromosome 2, cis-acting QTLs between 169 Mb and 182 Mb. The genes illustrated in green are the candidate genes located on chromosome 15 between 82 Mb and 92 Mb; phosphomannomutase1 (Pmm1), copine VIII (Cpne8), RAB, member of RAS oncogene family-like 2A (Rabl2a), and fibulin 1 (Fbln1).
Mentions: A correlative network graph and correlation matrices are additional ways to view this group of genes that form the core of the Gap43/Pten network. Using the tools available within GeneNetwork, a network graph was computed for the Gap43/Pten network. The eight genes form the core of the Gap43/Pten network (light blue) are shown in Figure 5. All of these genes possess expression levels that highly correlate across the BXD RI strains (r=0.5–1.0). The correlations between each of these genes are color coded in the network graph illustrated in Figure 5 and presented in Table 2. We find that the average range of correlation is between 0.54 and 0.95. The lowest correlation is between Id2 and Zbed4, with a value of 0.54, while the highest correlation (0.95) exists between Sox2 and Pax6.

Bottom Line: For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten).Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database.The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Center for Vision Research, Memphis, TN, USA.

ABSTRACT

Purpose: The present study examines the structure and covariance of endogenous variation in gene expression across the recently expanded family of C57BL/6J (B) X DBA/2J (D) Recombinant Inbred (BXD RI) strains of mice. This work is accompanied by a highly interactive database that can be used to generate and test specific hypotheses. For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten).

Methods: The Hamilton Eye Institute (HEI) Retina Database within GeneNetwork features the data analysis of 346 Illumina Sentrix BeadChip Arrays (mouse whole genome-6 version 2). 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/cByJ mice. Independent biologic samples for at least two animals from each gender were obtained with a narrow age range (48 to 118 days). Total RNA was prepared followed by the production of biotinylated cRNAs, which were pipetted into the Mouse WG-6V2 arrays. The data was globally normalized with rank invariant and stabilization (2z+8).

Results: The HEI Retina Database is located on the GeneNetwork website. The database was used to extract unique transcriptome signatures for specific cell types in the retina (retinal pigment epithelial, amacrine, and retinal ganglion cells). Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database. Bioinformatic tools located within GeneNetwork in conjunction with the HEI Retina Database were used to identify the unique signature Quantitative Trait Loci (QTLs) for Gap43 and Pten on chromosomes 1, 2, 12, 15, 16, and 19. Gap43 and Pten possess networks that are similar to ganglion cell networks that may be associated with axonal growth in the mouse retina. This network involves high correlations of transcription factors (SRY sex determining region Y-box 2 [Sox2], paired box gene 6 [Pax6], and neurogenic differentiation 1 [Neurod1]), and genes involved in DNA binding (proliferating cell nuclear antigen [Pcna] and zinc finger, BED-type containing 4 [Zbed4]), as well as an inhibitor of DNA binding (inhibitor of DNA binding 2, dominant negative helix-loop-helix protein [Id2]). Furthermore, we identified the potential upstream modifiers on chromosome 2 (teashirt zinc finger homeobox 2 [Tshz2], RNA export 1 homolog [Rae1] and basic helix-loop-helix domain contatining, class B4 [Bhlhb4]) on chromosome 15 (RAB, member of RAS oncogene family-like 2a [Rabl2a], phosphomannomutase 1 [Pmm1], copine VIII [Cpne8], and fibulin 1 [Fbln1]).

Conclusions: The endogenous variation in mRNA levels among BXD RI strains can be used to explore and test expression networks underlying variation in retina structure, function, and disease susceptibility. The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.

Show MeSH
Related in: MedlinePlus