Gene expression in pediatric heart disease with emphasis on conotruncal defects

Abstract

Developmental abnormalities of the heart are the underlying cause of many congenital heart malformations. The embryological development of the integrated cardiovascular tissue is the result of multiple tissue and cell-to-cell interactions involving temporal and spatial events under genetic control. Recent technological advances, like microarray analysis of gene expression, are providing new tools to aid in deciphering the complex networks of gene expression that regulate cardiac development. Here, we review our current understanding of the genetics of congenital heart disorders with emphasis on gene expression studies and report preliminary data from infants with conotruncal defects. We report our microarray analysis showing over-and underexpression of individual genes and gene network interactions from dysplastic pulmonic tissue from two infants with tetralogy of Fallot compared with normal pulmonic tissue from an unaffected control infant.

Whole genome microarray analysis of gene expression in subjects with fragile X syndrome

“…Four males with FXS (ages 16,20,28, and 38 years) and full mutations were similarly aged matched with four comparison males having normal intelligence (ages 15, 25, 28, and 30 years) and a pairwise analysis was performed based on age. In addition, frontal cortex brain samples were obtained from the Na- …”

“…20 The microarray data were initially filtered by setting all values at Ͻ0.01 to 0.01 to prevent spurious values Ͻ0. All samples were normalized to the median value of the control samples such that each measurement for each gene in each microarray was divided by the median of that gene's measurement in the corresponding control sample.…”

“…Differences between normalized mean gene expression levels were evaluated using a Welch t test with Bonferroni correction without assuming equal variances and a false discovery rate (fdr) of Յ20%, as undertaken in other studies. 22 We used the Ingenuity Pathways Analysis software (Ingenuity Systems, Mountain View, CA, http://www.ingenuity.com/ index.html) as previously described in similar studies 19,20 to examine the gene network interactions of the FMR1 gene and derived a list of 121 genes known to directly interact with FMR1 or FMRP for small group analysis (Fig. 1).…”

Rare Copy Number Variation Analysis in Chinese Children of Complete Atrioventricular Canal and Single Ventricle 

“…It has been well-known that RA is important for the development of the heart. INHBA (Inhibin Subunit Beta A) encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins, and it has been shown as a candidate gene for cardiac development [32].…”

Application of Pharmacogenomic Strategies to the Study of Drug-induced Birth Defects

“…The functional consequences of these perturbations should be more pronounced under conditions of high folate demand, especially in regions responsible for septation of the heart and formation of appropriate connections between atria and ventricles, and ventricles and great vessels—the atrioventricular and conotruncal cushions 21 . Although considerable information concerning the genetic basis of cardiac defects 22 and the gene‐regulatory networks involved in heart development is accumulating, 23 few data have been presented linking the theoretical consequences of folate dysregulation with specific changes in promoter methylation status or other events, leading to altered expression of these networks. Nevertheless, there is future promise in the assimilation of data derived from existing (microarrays 24 ) and new (whole‐genome methylation arrays 25 ) genomic tools, proteomic techniques, 26 and the availability of relevant human tissues through National Institutes of Health‐funded tissue repositories (the Central Laboratory for Human Embryology at the University of Washington, Seattle, WA, and the Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, MD).…”