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A tissue-specific gene expression template portrays heart development and pathology.

Rodemoyer A, Kibiryeva N, Bair A, Marshall J, O'Brien JE, Bittel DC - Hum. Genomics (2014)

Bottom Line: Tetralogy of Fallot (TOF) is a severe CHD that results from developmental defects in the conotruncal outflow tract.The GET, as previously defined, generally identified temporal and spatial differences in the cardiac tissue.Our analysis suggests that the homoeostatic equilibrium assessed by the GET at the inter-organ level is generally maintained at the intra-organ level as well.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Ward Family Heart Center, Children's Mercy Hospitals and Clinics, Kansas City, MO 64108, USA. dbittel@cmh.edu.

ABSTRACT
Congenital heart defects (CHD) are the most common cause of death in children under the age of 1. Tetralogy of Fallot (TOF) is a severe CHD that results from developmental defects in the conotruncal outflow tract. Recently, a tissue-specific gene expression template (GET) was derived from microarray data that accurately characterized multiple normal human tissues. We used the GET to examine spatial, temporal, and a pathological condition (TOF) within a single organ, the heart. The GET, as previously defined, generally identified temporal and spatial differences in the cardiac tissue. Differences in the stoichiometry of the GET reflected the severe developmental disturbance associated with TOF. Our analysis suggests that the homoeostatic equilibrium assessed by the GET at the inter-organ level is generally maintained at the intra-organ level as well.

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Interactive network of GET genes with shared expression patterns between TOF RV and adult LV. Interactive network of genes associated with the GET with shared expression patterns in TOF and adult LV compared to normally developing infant RV. Genes in gray are from the GET.
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Figure 3: Interactive network of GET genes with shared expression patterns between TOF RV and adult LV. Interactive network of genes associated with the GET with shared expression patterns in TOF and adult LV compared to normally developing infant RV. Genes in gray are from the GET.

Mentions: There were 19 GET genes with statistically significant changes in expression between TOF RV and normally developing infant RV but were unchanged between TOF RV and adult LV (marked with an ‘x’ in Additional file 2: Table S2). We reasoned that these genes might represent networks functioning in common between TOF and adult LV which might suggest a physiological explanation for the clustering pattern. The most statistically significant functional network identified using IPA (see ‘Methods’ for explanation of bioinformatic assessment) contained 10 of the 19 GET genes and formed an interactive network involved broadly in gene expression, cell signaling, and cell growth. More specifically, several members of this network are known to be involved in cardiac development, myogenesis, and cardiac hypertrophy (Figure 3). These comparisons specifically substantiate the hypothesis that pathological conditions are associated with the significant deviation from normal biochemical stoichiometry which can be represented by the expression patterns of a small number of key genes.


A tissue-specific gene expression template portrays heart development and pathology.

Rodemoyer A, Kibiryeva N, Bair A, Marshall J, O'Brien JE, Bittel DC - Hum. Genomics (2014)

Interactive network of GET genes with shared expression patterns between TOF RV and adult LV. Interactive network of genes associated with the GET with shared expression patterns in TOF and adult LV compared to normally developing infant RV. Genes in gray are from the GET.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4007492&req=5

Figure 3: Interactive network of GET genes with shared expression patterns between TOF RV and adult LV. Interactive network of genes associated with the GET with shared expression patterns in TOF and adult LV compared to normally developing infant RV. Genes in gray are from the GET.
Mentions: There were 19 GET genes with statistically significant changes in expression between TOF RV and normally developing infant RV but were unchanged between TOF RV and adult LV (marked with an ‘x’ in Additional file 2: Table S2). We reasoned that these genes might represent networks functioning in common between TOF and adult LV which might suggest a physiological explanation for the clustering pattern. The most statistically significant functional network identified using IPA (see ‘Methods’ for explanation of bioinformatic assessment) contained 10 of the 19 GET genes and formed an interactive network involved broadly in gene expression, cell signaling, and cell growth. More specifically, several members of this network are known to be involved in cardiac development, myogenesis, and cardiac hypertrophy (Figure 3). These comparisons specifically substantiate the hypothesis that pathological conditions are associated with the significant deviation from normal biochemical stoichiometry which can be represented by the expression patterns of a small number of key genes.

Bottom Line: Tetralogy of Fallot (TOF) is a severe CHD that results from developmental defects in the conotruncal outflow tract.The GET, as previously defined, generally identified temporal and spatial differences in the cardiac tissue.Our analysis suggests that the homoeostatic equilibrium assessed by the GET at the inter-organ level is generally maintained at the intra-organ level as well.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Ward Family Heart Center, Children's Mercy Hospitals and Clinics, Kansas City, MO 64108, USA. dbittel@cmh.edu.

ABSTRACT
Congenital heart defects (CHD) are the most common cause of death in children under the age of 1. Tetralogy of Fallot (TOF) is a severe CHD that results from developmental defects in the conotruncal outflow tract. Recently, a tissue-specific gene expression template (GET) was derived from microarray data that accurately characterized multiple normal human tissues. We used the GET to examine spatial, temporal, and a pathological condition (TOF) within a single organ, the heart. The GET, as previously defined, generally identified temporal and spatial differences in the cardiac tissue. Differences in the stoichiometry of the GET reflected the severe developmental disturbance associated with TOF. Our analysis suggests that the homoeostatic equilibrium assessed by the GET at the inter-organ level is generally maintained at the intra-organ level as well.

Show MeSH
Related in: MedlinePlus