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Gene expression changes between patent and fused cranial sutures in a nonsyndromic craniosynostosis population.

Potter AB, Rhodes JL, Vega RA, Ridder T, Shiang R - Eplasty (2015)

Bottom Line: SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures.SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

View Article: PubMed Central - PubMed

Affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland.

ABSTRACT

Objective: Craniosynostosis is a premature fusion of 1 or more cranial sutures. It may occur with additional morphological abnormalities (syndromic) or in isolation. Studies suggest that dysregulation of normal cell proliferation, differentiation, and migration has a role in isolated or nonsyndromic craniosynostosis but the molecular mechanisms remain unknown. The aim of this research is to identify genes differentially expressed in prematurely fused human suture compared to patent suture in nonsyndromic craniosynostosis.

Methods: Bone fragments from synostosed and patent sutures of 7 infants with nonsyndromic craniosynostosis were collected during surgical release of fused sutures. RNA was isolated from the fragments (7 patent and 7 fused) and global gene expression profiled using the Illumina WGE-DASL assay and HumanRef 8.0 Beadchip.

Results: Comparison of mRNA expression in fused and patent suture identified 68 genes significantly differentially expressed and having fold changes ≤ -2.0 and ≥ 2.0 with a false discovery rate adjusted P value at .10 and 136 with adjusted P value of 0.15. SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures. Analysis including only sagittal fused sutures revealed a set of 35 overlapping genes that may be involved in suture patency over all suture types. SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.

Conclusion: Differentially expressed genes were identified in fused suture relative to patent in a nonsyndromic craniosynostosis population. SFRP2 is likely important in suture patency. Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

No MeSH data available.


Related in: MedlinePlus

Pathway analysis. De novo pathway analysis using the false discovery rate (FDR) 0.15 gene list. Pathways were built with Ingenuity Pathway Analysis taking the genes with significant gene expressions changes from this experiment and identifying known relationships between the genes. Green indicates genes downregulated and red indicates upregulated genes from this study. The white genes did not have significant gene expression changes but link the genes in the network that are significantly changed. The intensity of the color indicates the degree of the expression change. Solid lines indicate direct interaction, while dashed lines indicate indirect interaction. Lines indicate binding between molecules, while arrows indicate molecule that can act on another which may or may not also bind.
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Figure 2: Pathway analysis. De novo pathway analysis using the false discovery rate (FDR) 0.15 gene list. Pathways were built with Ingenuity Pathway Analysis taking the genes with significant gene expressions changes from this experiment and identifying known relationships between the genes. Green indicates genes downregulated and red indicates upregulated genes from this study. The white genes did not have significant gene expression changes but link the genes in the network that are significantly changed. The intensity of the color indicates the degree of the expression change. Solid lines indicate direct interaction, while dashed lines indicate indirect interaction. Lines indicate binding between molecules, while arrows indicate molecule that can act on another which may or may not also bind.

Mentions: FDR 0.10 and 0.15 gene lists and fold changes were evaluated through the Ingenuity Pathway Analysis (IPA) (Ingenuity® Systems, www.ingenuity.com) specifically de novo network analyses and predictions of upstream activators and inhibiters were most useful in analysis of the gene sets. The de novo network analysis used the gene lists derived from the microarray data from these experiments and found known relationships between the genes that created the pathways (Figs 1 and 2). Genes not on the list may be inserted into the pathways to make connections between the genes. Venny was used to create Venn diagrams to identify overlap of genes between studies.7-9,12 Chi-square analysis with Yates correction was used to determine the significance of overlapping genes (GraphPad).


Gene expression changes between patent and fused cranial sutures in a nonsyndromic craniosynostosis population.

Potter AB, Rhodes JL, Vega RA, Ridder T, Shiang R - Eplasty (2015)

Pathway analysis. De novo pathway analysis using the false discovery rate (FDR) 0.15 gene list. Pathways were built with Ingenuity Pathway Analysis taking the genes with significant gene expressions changes from this experiment and identifying known relationships between the genes. Green indicates genes downregulated and red indicates upregulated genes from this study. The white genes did not have significant gene expression changes but link the genes in the network that are significantly changed. The intensity of the color indicates the degree of the expression change. Solid lines indicate direct interaction, while dashed lines indicate indirect interaction. Lines indicate binding between molecules, while arrows indicate molecule that can act on another which may or may not also bind.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401998&req=5

Figure 2: Pathway analysis. De novo pathway analysis using the false discovery rate (FDR) 0.15 gene list. Pathways were built with Ingenuity Pathway Analysis taking the genes with significant gene expressions changes from this experiment and identifying known relationships between the genes. Green indicates genes downregulated and red indicates upregulated genes from this study. The white genes did not have significant gene expression changes but link the genes in the network that are significantly changed. The intensity of the color indicates the degree of the expression change. Solid lines indicate direct interaction, while dashed lines indicate indirect interaction. Lines indicate binding between molecules, while arrows indicate molecule that can act on another which may or may not also bind.
Mentions: FDR 0.10 and 0.15 gene lists and fold changes were evaluated through the Ingenuity Pathway Analysis (IPA) (Ingenuity® Systems, www.ingenuity.com) specifically de novo network analyses and predictions of upstream activators and inhibiters were most useful in analysis of the gene sets. The de novo network analysis used the gene lists derived from the microarray data from these experiments and found known relationships between the genes that created the pathways (Figs 1 and 2). Genes not on the list may be inserted into the pathways to make connections between the genes. Venny was used to create Venn diagrams to identify overlap of genes between studies.7-9,12 Chi-square analysis with Yates correction was used to determine the significance of overlapping genes (GraphPad).

Bottom Line: SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures.SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

View Article: PubMed Central - PubMed

Affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland.

ABSTRACT

Objective: Craniosynostosis is a premature fusion of 1 or more cranial sutures. It may occur with additional morphological abnormalities (syndromic) or in isolation. Studies suggest that dysregulation of normal cell proliferation, differentiation, and migration has a role in isolated or nonsyndromic craniosynostosis but the molecular mechanisms remain unknown. The aim of this research is to identify genes differentially expressed in prematurely fused human suture compared to patent suture in nonsyndromic craniosynostosis.

Methods: Bone fragments from synostosed and patent sutures of 7 infants with nonsyndromic craniosynostosis were collected during surgical release of fused sutures. RNA was isolated from the fragments (7 patent and 7 fused) and global gene expression profiled using the Illumina WGE-DASL assay and HumanRef 8.0 Beadchip.

Results: Comparison of mRNA expression in fused and patent suture identified 68 genes significantly differentially expressed and having fold changes ≤ -2.0 and ≥ 2.0 with a false discovery rate adjusted P value at .10 and 136 with adjusted P value of 0.15. SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures. Analysis including only sagittal fused sutures revealed a set of 35 overlapping genes that may be involved in suture patency over all suture types. SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.

Conclusion: Differentially expressed genes were identified in fused suture relative to patent in a nonsyndromic craniosynostosis population. SFRP2 is likely important in suture patency. Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

No MeSH data available.


Related in: MedlinePlus