Expression data from euploid and trisomic 13, 18 and 21 human fetal cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65055 | GEO | 2015/10/09
SECONDARY ACCESSION(S): PRJNA272805
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome, DS), 18 (Edward syndrome, ES) and 13 (Patau syndrome, PS) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effects due to the trisomic chromosome, a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to define whether (1) overexpression of genes of the trisomic chromosome contributes solely to the phenotype, if (2) all genes of the trisomic chromosome are upregulated similarly and whether the ratio of gene expression is in agreement with the gene dosis, (3) whether the different trisomies behave similarly in the characteristics of transcriptional dysregulation, and (4) whether transcriptional pattern can be potentially used in prenatal diagnosis. Methods: Using oligonucleotide microarrays (Affymetrix, U133 Plus 2.0), we analyzed whole genome expression profiles representing 54.000 probe sets in cultured amniocytes (AC) and chorion villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 21, 18 and 13. Findings: We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional level of approximately 12-13 % of the supernumerary chromosome appeared similar to the respective chromosome pair in normal karyotypes. Expression values as well as the expression patterns of genes from the trisomic chromosome can distinguish the respective trisomic samples from euploid controls. A subset of chromosome 21-genes including the DSCR1-gene involved in fetal heart development was consistently up-regulated in different tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 13 and trisomy 18 vigorous downstream transcriptional changes were found. Interpretation: Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. As several transcriptional pathways are altered, complex regulatory mechanisms are involved in the pathogenesis of autosomal trisomies. A genome-wide transcriptional dysregulation was predominantly observed in trisomies 13 and 18, whereas a more to chromosome 21 restricted expression alteration was found in trisomy 21. Experiment Overall Design: The study included the following samples: Three samples with normal chromosomes in Amniocytes (AC) and chorion villus cells (CV) each, three samples with trisomy 13 in AC, three samples with trisomy 18 in CV, and three samples with trisomy 21 in AC and CV each.
2008-06-14 | E-GEOD-6283 | biostudies-arrayexpress
Project description:Several studies have investigated the gene expression profiles in trisomies 21 and 18 to identify the expression signatures that are characteristic of each of these specific aneuploidy conditions. We hypothesized that the viability of cells with gross genomic imbalances might be associated with the activation of resilience mechanisms that are common to different trisomies and that are reflected by specific shared gene expression patterns. Microarray gene expression analysis of amniocytes from fetuses with trisomy 21 or trisomy 18 was conducted to detect such common expression signatures. Comparative analysis of significantly differentially expressed genes in trisomies 18 and 21 identified 6 dysregulated genes common to both trisomies: OTUD5, ADAMTSL1, TADA2A, PPID, PIAS2, and MAPRE2. These genes are involved in apoptosis, ubiquitination, protein folding, and cell division. Functional analysis demonstrated that both trisomies showed dysregulation of the PI3K/AKT pathway, cell cycle G2/M DNA damage checkpoint regulation, and cell death and survival, as well as inhibition of the upstream regulator TP53. Our data demonstrated that trisomies 18 and 21 share common gene expression signatures, implying that common mechanisms of resilience might be activated in aneuploid cells to resist large genomic imbalances. Studies of other trisomies might further clarify mechanisms activated in trisomy syndromes.
2016-11-13 | GSE89782 | GEO
Project description:Background: Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome, DS), 18 (Edward syndrome, ES) and 13 (Patau syndrome, PS) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effects due to the trisomic chromosome, a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to define whether (1) overexpression of genes of the trisomic chromosome contributes solely to the phenotype, if (2) all genes of the trisomic chromosome are upregulated similarly and whether the ratio of gene expression is in agreement with the gene dosis, (3) whether the different trisomies behave similarly in the characteristics of transcriptional dysregulation, and (4) whether transcriptional pattern can be potentially used in prenatal diagnosis. Methods: Using oligonucleotide microarrays (Affymetrix, U133 Plus 2.0), we analyzed whole genome expression profiles representing 54.000 probe sets in cultured amniocytes (AC) and chorion villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 21, 18 and 13. Findings: We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional level of approximately 12-13 % of the supernumerary chromosome appeared similar to the respective chromosome pair in normal karyotypes. Expression values as well as the expression patterns of genes from the trisomic chromosome can distinguish the respective trisomic samples from euploid controls. A subset of chromosome 21-genes including the DSCR1-gene involved in fetal heart development was consistently up-regulated in different tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 13 and trisomy 18 vigorous downstream transcriptional changes were found. Interpretation: Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. As several transcriptional pathways are altered, complex regulatory mechanisms are involved in the pathogenesis of autosomal trisomies. A genome-wide transcriptional dysregulation was predominantly observed in trisomies 13 and 18, whereas a more to chromosome 21 restricted expression alteration was found in trisomy 21. Keywords: Trisomy, Down syndrome, Patau syndrome, Edward syndrome, microarray, gene expression, amniocytes, chorion villus cells, gene dosage effect, DSCR1
2006-12-01 | GSE6283 | GEO
Project description:Phenotypes in chromosome abnormalities do not arise as a mere summation of the specific effects of dosage-sensitive genes, but as a result of the synergistic actions of whole chromosomes. Recent studies on yeast and mammalian cells have demonstrated that aneuploidy exerts detrimental effects on organismal growth and development, regardless of the karyotype, suggesting that aneuploidy-associated stress plays an important role in disease pathogenesis. However, whether and how this effect alters cellular homeostasis and long-term features of human disease are not fully understood. Here, we aimed to investigate cellular stress responses in human trisomy syndromes, using fibroblasts and induced pluripotent stem cells (iPSCs). Dermal fibroblasts derived from patients with trisomy 21, 18 and 13 showed a severe impairment of cell proliferation and enhanced premature senescence. These phenomena were accompanied by perturbation of protein homeostasis, leading to the accumulation of protein aggregates. We found that treatment with sodium 4-phenylbutyrate (4-PBA), a chemical chaperone, decreased the protein aggregates in trisomy fibroblasts. Notably, 4-PBA treatment successfully prevented the progression of premature senescence in secondary fibroblasts derived from trisomy 21 iPSCs. Our study reveals aneuploidy-associated stress as a potential therapeutic target for human trisomies, including Down syndrome.
2019-07-18 | GSE120291 | GEO
Project description:Congenital development disorders with variable severity occur in trisomy 21. However, how these phenotypic abnormalities develop with variations remains elusive. We hypothesize that the difference in euploidy gene expression variation among trisomy 21 tissues are perturbed by the presence of an extra copy of chromosome 21 and this may contribute to the phenotypic variations in Down syndrome. Experiment Overall Design: We used DNA microarray to measure the differences in gene expression variance (representing variation) between four human trisomy 21 amniocytes and six human euploid amniocytes.
2008-04-03 | E-GEOD-10758 | biostudies-arrayexpress
Project description:Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied high-throughput chromo-some conformation capture technique (Hi-C) to study chromatin 3D structure in human donor chorion cells carrying additional chromosome 13 (Patau syndrome), chromosome 16 (the most common trisomy), and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes 13 and 16, but not 18, results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chro-mosomes, we determined that a limited number of chromosomes change their contact patterns stochastically in trisomic cells, and that it could be linked to LAD and gene content. We also found that genome regions which are more compacted in trisomic cells are significantly enriched in housekeeping genes that potentially suggest the decrease of chromatin accessibility and tran-scription level. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organi-zation.
2023-12-08 | GSE237372 | GEO
Project description:To characterize aneuploidy driven phenotypes in human trisomies, we performed global transcriptome, proteome, and phenotypic analysis of primary human fibroblasts from individuals with Patau (trisomy 13), Edwards (trisomy 18), or Down syndromes.
2020-07-09 | MSV000085706 | MassIVE
Project description:Transcriptome profiling uncovers potential common mechanisms in fetal trisomies 18 and 21
| PRJNA353275 | ENA
Project description:To understand the molecular mechanisms underlying the congenital anomalies observed in patients with Trisomy 18, we compared gene expression in uncultured amniotic fluid supernatant samples from second trimester fetuses with Trisomy 18 and from euploid controls. Analysis of differential expression using both individual-gene and gene-set or pathway methods indicated disrupted function in ion transport, MHCII/T-cell mediated immunity, DNA repair, G-protein mediated signaling, kinases, and glycosylation. Significant down-regulation of genes involved in adrenal development was also identified in the trisomic fetuses, possibly explaining both the abnormal maternal serum estriols and the pre- and postnatal growth restriction found in this condition.
2010-12-03 | GSE25634 | GEO
Project description:Down syndrome (DS), caused by an extra copy of chromosome 21, affects 1 in 750 live births and is characterised by cognitive impairment and a constellation of congenital defects. Currently, little is known about the molecular pathogenesis and no direct genotype-phenotype relationship has yet been confirmed. Since DS amniocytes are expected to have a distinct biological behaviour compared to normal amniocytes, we hypothesise that relative quantification of proteins produced from trisomy and euploid (chromosomally normal) amniocytes will reveal dysregulated molecular pathways. Chromosomally normal- and Trisomy 21-amniocytes were quantitatively analyzed by using Stable Isotope Labeling of Amino acids in Cell culture and tandem mass spectrometry. The most extensive proteome of amniocytes and amniotic fluid has been generated and differentially expressed proteins from amniocytes with Trisomy 21 revealed molecular pathways that seem to be most significantly affected by the presence of an extra copy of chromosome 21. Mass spectra were analyzed using Mascot (version 2.2, Matrix Science), executing a spectral search against a concatenated International Protein Index (IPI) human protein database (version 3.54 containing 39,925 entries) and a decoy database. Parameters included: trypsin enzyme specificity, SILAC double measurements of Lys6 and Arg8, 1 missed cleavage, minimum peptide length of 7 amino acids, minimum of 1 unique peptide, top 6 MS/MS peaks per 100 Da, peptide mass tolerance of 20 ppm for precursor ion and MS/MS tolerance of 0.5 Da. Oxidation of methionine and N-terminal protein acetylation for variable modifications and cysteine caramidomethylation for fixed modification. All entries were filtered using a false positive rate of 1% both at the peptide and protein levels, and false positives were removed. Quantification via normalised H/L ratios was based on minimum of 3 peptide ratio counts. Protein group entries with a normalised ratio significance B score of =< 0.05 or significance A score of =< 0.05 were retained for further analysis.
2013-09-27 | PXD000385 | Pride