Gene Expression Profiling in 45X Turner Syndrome patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE46687 | GEO | 2014/03/01
SECONDARY ACCESSION(S): PRJNA203117
REPOSITORIES: GEO
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Project description:Turner Syndrome (TS) is the most common X chromosome aneuploidy disorder in female, and the predominant karyotype is 45X, a complete loss of the second sex chromosome. Depending on the parental origin of the single X chromosome, 45X patients can be further divided into two groups: 45Xm and 45Xp with maternal and paternal inherited X chromosome, respectively. TS patients of 45Xm and 45Xp are found to associate with different severity in phenotype, including prevalence for cardiovascular disease. To study parental X chromosome impact to TS phenotype, differential gene expression in PBMC of 45Xm and 45Xp was analyzed by microarray. Gene expression for normal female 46XX was also analyzed in parallel to investigate the whole genome-wide gene expression changes between monosomy X TS patients and normal females.
2014-03-01 | E-GEOD-46687 | biostudies-arrayexpress
Project description:Turner Syndrome (TS) is a rare cytogenetic disorder caused by the complete loss or structural variation of the second sex chromosome. The most common cause of early mortality in TS results from a high incidence of left-sided congenital heart defects, including bicuspid aortic valve (BAV), which occurs in about 30% of individuals with TS. BAV is also the most common congenital heart defect in the general population with a prevalence of 0.5-2%, with males being three-times more likely to have a BAV than females. TS is associated with genome wide hypomethylation when compared to karyotypically normal males and females. Alterations in DNA methylation in primary aortic tissue are associated with BAV in euploid individuals. Here we show significant differences in DNA methylation patterns associated with BAV in TS found in peripheral blood. When comparing TS with BAV to TS with no heart defects we identified a differentially methylated region encompassing the BAV-associated gene MYRF, and enrichment for binding sites of two known transcription factor contributors to BAV. When comparing TS with BAV to euploid women with BAV, we found significant overlapping enrichment for ChIP-seq transcription factor targets including genes in the NOTCH1 pathway, known for involvement in the etiology of non-syndromic BAV, and other genes that are essential regulators of heart valve development. Overall, these findings suggest that altered DNA methylation affecting key aortic valve development genes contributes to the greatly increased risk for BAV in TS.
2022-03-12 | GSE198262 | GEO
Project description:Heart deformity is the leading cause of mortality in Turner syndrome (TS) patients. To investigate the dysregulated ceRNA network in cardiomyocytes (CMs) of TS patients, we employed a ceRNA microarray to profile the mRNA-lncRNA-circRNA network in induced pluripotent stem cells (iPSCs) and their derived CMs from healthy donors (WT) and TS patients.
2023-08-06 | GSE239758 | GEO
Project description:We have generated iPSCs from monosomy X (Turner Syndrome), trisomy 8 (Warkany Syndrome 2), trisomy 13 (Patau Syndrome) and partial trisomy 11;22 (Emanuel Syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells (ESCs) in all tested assays. Turner Syndrome iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body (EB) formation. These data support that abnormal organogenesis and early lethality in Turner Syndrome are not caused by a tissue-specific differentiation blockade but rather involves other abnormalities including impaired placentation. Global gene expression profiling with DNA microarrays showed that 3 TS iPSC clones corresponding to the same patient showed a global gene expression pattern similar to ESCs and euploid iPSCs, and very different from donor cells .We detected transcriptomic changes between TS iPSCs and the other ESCs/iPSCs but these variations did not follow a pattern and in fact all pluripotent cell lines clustered together. For DNA microarray analysis, all cells were treated with Trizol, followed by RNA extraction and hybridization.
2011-10-03 | E-GEOD-32527 | biostudies-arrayexpress
Project description:The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly occurs in females who have either a partial or complete loss of one of their X chromosomes. Our understanding of the role granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited. Here, we elevated GC differentiation efficiency up to the level of 80% differentiated cells from iPSCs. In our attempt to replicate the differentiation process of embryonic granulosa cells, we observed that specific genes—GATA4, FOXL2, AMHR2, CYP19A1, and FSH—were downregulated in Turner syndrome-derived granulosa cells (TS-GCs). Additionally, dysregulation of the cell cycle was observed in TS-GCs. To reveal the endogenous defects in the TS-GCs, we conducted a comparison of the global transcriptome patterns between differentiated granulosa cells derived from iPSCs in both healthy and Turner syndrome groups. The apelin/APJ pathway displayed a differential between the healthy and TS groups. Supplementation of apelin ligands and activation of apelin/APJ downstream signals via Akt/PKB restored the cell cycle progression and marker gene expression. We hypothesize that during early embryonic development failures in apelin/APJ signaling in GCs in Turner syndrome patients leads to abnormalities in ovarian development and consequently to early loss of oocytes and infertility.
2024-11-20 | GSE271780 | GEO
Project description:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChip® Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a “Turner syndrome core transcriptome”), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study.
2014-06-13 | GSE58435 | GEO
Project description:Background: In both Turner syndrome (TS) and Klinefelter syndrome (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. To date there has not been a comprehensive and directly comparative analysis of TS vs. KS regarding the changes on the molecular level Methods: We analyzed gene expression patterns with RNA-Seq and DNA methylation patterns with the CpGiant assay in lymphocytes, and chromatin conformation with in situ Hi-C in lymphoblastoid cell lines, from TS and KS patients together with their same gender controls. Results: In TS, differentially expressed escape genes were downregulated but differentially expressed inactive genes were upregulated. In KS, differentially expressed escape genes were upregulated while inactive genes appeared unchanged. Interestingly, 81 differentially expressed genes (DEGs) were associated with both TS and KS, and uniformly displayed expression changes into opposite directions. DEGs on the X chromosome and the autosomes were coexpressed in both TS and KS, indicating that there are molecular ripple effects of the changes in X chromosome dosage that extend to autosomes. Four potentially candidate genes (RPS4X, SEPT6, NKRF and CX0rf57) for KS were identified on Xq. Broad hypomethylation of the X chromosome is observed in TS whereas hypermethylation of chromosome X is present in KS. Only promoters of inactive genes were differentially methylated in both TS and KS while escape genes remained unchanged. The intrachromosomal contact map of the X chromosome in TS was partitioned into two superdomains and exhibited the structure of an active X chromosome. Conclusions: Components of the molecular basis of TS and KS were identified on the levels of the transcriptome and the epigenome, with candidate central genes on Xp for TS and on Xq for KS. The discovery of shared DEGs indicates the existence of common molecular mechanisms for gene regulation in TS and KS that are transmitting the gene dosage changes to the transcriptome.
2020-02-28 | GSE126712 | GEO
Project description:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChipM-BM-. Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a M-bM-^@M-^\Turner syndrome core transcriptomeM-bM-^@M-^]), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study. 2nd trimester amniotic fluid mRNA expression was compared between 5 Turners and 5 euploid fetuses.
2014-06-13 | E-GEOD-58435 | biostudies-arrayexpress
Project description:We have generated iPSCs from monosomy X (Turner Syndrome), trisomy 8 (Warkany Syndrome 2), trisomy 13 (Patau Syndrome) and partial trisomy 11;22 (Emanuel Syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells (ESCs) in all tested assays. Turner Syndrome iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body (EB) formation. These data support that abnormal organogenesis and early lethality in Turner Syndrome are not caused by a tissue-specific differentiation blockade but rather involves other abnormalities including impaired placentation.
2011-10-04 | GSE32527 | GEO
Project description:X chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell. In order to characterize epigenetic changes that accompany this process, we measured DNA methylation levels in both 45,X Turner syndrome patients, who carry a single active X chromosome (Xa) and normal 46,XX females, who carry one Xa and one inactive X (Xi). Methylated DNA was immunoprecipitated and hybridized to tiling oligonucleotide arrays, generating epigenetic profiles of active and inactive X chromosomes. We observed that XCI is accompanied by changes in DNA methylation specifically at CpG islands. While the majority of CpG islands show increased methylation levels on the Xi, XCI results in reduced methylation at ~20% of CpG islands. Both intra- and inter-genic CpG islands are epigenetically modified, with the biggest increase in methylation occuring at the promoters of genes silenced by XCI. In contrast, genes escaping XCI have low levels of promoter methylation, while genes that undergo polymorphic silencing show intermediate increases in methylation proportionate to their frequency of inactivation. Thus promoter methylation and susceptibility to XCI are correlated. We observed a global correlation between CpG island methylation and the evolutionary age of different X chromosome strata, and that genes escaping XCI show increased methylation within gene bodies. We utilized our epigenetic map to predict both novel genes escaping XCI, and to identify sequence features that may contribute to the XCI process. Finally, as our study included Turner syndrome patients with single X chromosomes of both maternal and paternal origin we searched for parent-of-origin specific methylation differences, but found no evidence to support imprinting on the human X chromosome. Our study provides the first epigenetic profile of active and inactive X chromosomes, giving novel insights into the phenomenon of dosage compensation. Methylated DNA was enriched by immunoprecipitation using antibodies against 5-methylcytosine. meDIP and input DNA was labeled with cy5 and cy3 respectively and hybridized to Nimblegen arrays comprising 2.1 million 50-85mers covering human chromosomes 20, 21, 22, X and Y at a mean density of ~1 probe per 100bp. Resulting log2 fluorescence ratios correspond to methylation levels. Seven patients with Turner syndrome (45,X karyotype), and three normal females (46,XX karyotype) were analyzed. Of the Turner syndrome cases, four had a maternally-derived X, and three had a paternally-derived X chromosome.
2010-07-20 | E-GEOD-22551 | biostudies-arrayexpress