Project description:This SuperSeries is composed of the following subset Series: GSE34457: Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines (congenital heart disease) GSE34458: Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines (trisomy 21) Refer to individual Series
Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21.
Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines. In this study, we want to identify genes and pathways specifically dysregulated in atrioventricular septal defect and /or atrial septal defect + ventricular septal defect in case of trisomy 21. Total RNA obtained from DS lymphoblastoid cell lines without congenital heart disease compared to cell lines from DS with congenital heart disease.
Project description:Molecular consequences of trisomy in lymphoblastoid cell lines from patients with Down syndrome. This project analyses differentially expressed genes between humans with trisomy 21 and humans without trisomy 21.
2012-08-15 | GSE34458 | GEO
Project description:Molecular Signatures of cardiac defects in Down syndrome lymphoblastoid cell lines
Project description:Molecular consequences of trisomy in lymphoblastoid cell lines from patients with Down syndrome. This project analyses differentially expressed genes between humans with trisomy 21 and humans without trisomy 21. Total RNA obtained from human lymphoblastoid cell lines without trisomy 21 compared to cell lines from human with trisomy 21.
Project description:Background: Down syndrome is the most common genetic cause of mental retardation in humans, occurring in ~1 in 800 newborns. It is caused by chromosome 21 trisomy. Disruption of the phenotype is thought to be the result of gene dosage imbalance. The aim of the study was to classify chromosome 21 genes according to their level of expression in Down syndrome. Results: Variations in chromosome 21 gene expression were analyzed in lymphoblastoid cell lines derived from 10 Down syndrome patients and 11 control individuals. Of the 359 genes and predictions displayed on a specifically designed high content chromosome 21 oligoarray, 132 genes were expressed in lymphoblastoid cell lines. By using a powerful statistical analysis, 58 genes were found overexpressed and 42 unchanged in cell lines from Down syndrome patients. Microarray data were validated by quantitative PCR on 10 genes. Conclusions: The 132 chromosome 21 genes expressed by derived lymphoblastoid cell lines were classified into four categories: Class I: 24 genes controlled by the gene dosage effect with an increase in expression in Down syndrome between 1.4 and 1.6; Class II: 14 amplified genes with expression ratio above 1.6; Class III: 32 compensated genes with expression ratio between 0.82 to 1.4 and Class IV: 30 genes with high variability between individuals. Class I and II genes are likely to be involved in the Down syndrome phenotype, in contrast to the compensated Class III genes; Class IV genes could account for the variable phenotypes observed in patients. Keywords: HSA21 gene expression in Down syndrome
Project description:Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contribute to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. mRNA-seq profiling of iPS cells (4 euploid and 3 trisomy 21) derived from fibroblasts of monozygotic twins discordant for trisomy 21
Project description:Gene expression was measured in trisomy 21 and trisomy 13 human fetal samples. For TS21, regions assayed were cerebrum, cerebellum, heart, and cerebrum-derived astrocyte cell lines. Keywords = trisomy 21 Keywords = Down syndrome Keywords = aneuploidy Keywords = brain Keywords = heart Keywords = trisomy 13 Keywords: other
