Aberrant expression of lncRNAs in autistic brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36315 | GEO | 2012/09/10
SECONDARY ACCESSION(S): PRJNA153355
REPOSITORIES: GEO
Similar Datasets
Project description:To assess for the potential contribution of dysregulated long non-coding RNA expression in autism pathogenesis, we profiled lncRNAs and mRNAs from post mortem brain tissue from autism patients and age/sex matched controls 4 brain tissue samples from autism patients (2 patients, 1 prefrontal cortex and cerebellum sample from each) were compared to 4 brain tissue samples from non-affected controls (2 patients, 1 prefrontal cortex and cerebellum sample from each)
2012-09-10 | E-GEOD-36315 | biostudies-arrayexpress
Project description:In this study, we investigated PPA-induced changes in gene expression profiles of lymphoblastoid cell lines (LCLs) from unaffected individuals, compared with gene expression profiles of LCLs from sex-matched siblings with ASD. Global gene expression profiling analysis revealed that 96 genes in LCLs from the unaffected individuals were significantly altered after PPA exposure, exhibiting expression levels similar to those of their respective siblings with autism. Biological pathway analyses of these PPA-responsive genes suggested significant association with many neurological functions associated with autism, including synaptic transmission, neuronal cell differentiation and apoptosis. Moreover, we demonstrated that PPA also deregulated several of the responsive genes, including APOE, LIFR, NR3C1, and PTK2, in the neuroblastoma cell line SH-SY5Y. Functional analyses further showed that PPA exposure negatively impacted neurite outgrowth and promoted neurodegeneration in the human neuronal cell model. This study indicates that PPA exposure induces global changes in gene expression profiles of LCLs from non-autistic individuals that reflect expression patterns of LCLs from affected individuals.
2011-09-16 | GSE32136 | GEO
Project description:In this study, we investigated PPA-induced changes in gene expression profiles of lymphoblastoid cell lines (LCLs) from unaffected individuals, compared with gene expression profiles of LCLs from sex-matched siblings with ASD. Global gene expression profiling analysis revealed that 96 genes in LCLs from the unaffected individuals were significantly altered after PPA exposure, exhibiting expression levels similar to those of their respective siblings with autism. Biological pathway analyses of these PPA-responsive genes suggested significant association with many neurological functions associated with autism, including synaptic transmission, neuronal cell differentiation and apoptosis. Moreover, we demonstrated that PPA also deregulated several of the responsive genes, including APOE, LIFR, NR3C1, and PTK2, in the neuroblastoma cell line SH-SY5Y. Functional analyses further showed that PPA exposure negatively impacted neurite outgrowth and promoted neurodegeneration in the human neuronal cell model. This study indicates that PPA exposure induces global changes in gene expression profiles of LCLs from non-autistic individuals that reflect expression patterns of LCLs from affected individuals. We conducted experiments using LCLs derived from individuals with ASD (n = 5) and their sex-matched unaffected siblings (n = 5). LCLs from non-ASD individuals were treated with 10 mM PPA, 10 mM propanol, or PBS. LCLs from individuals with ASD were treated with 10 mM propanol or PBS. At 24h after treatment, all LCLs were harvested. Gene expression profiling was conducted using TIGR 40K human cDNA microarrays. For each sample, total RNA was isolated and cDNA was synthesized, labeled with Cy-3 dye, and co-hybridized with Cy-5 labeled reference cDNA prepared from Universal human RNA (Stratagene, USA) on a TIGR 40K human cDNA microarray.
2011-09-15 | E-GEOD-32136 | biostudies-arrayexpress
Project description:Background: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. We want to study the lncRNAs profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent demonstrating that the placenta is sufficient to cause the condition. So we analyze the lncRNAs profiles in preeclampsia placentas. In this study, we described the lncRNAs profiles in 6 preeclampsia placentas (T) and 5 matched normal pregnancy placentas (N) tissues by microarray. Methodology/Principal Findings: With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 28,443. From the data we found there were 738 lncRNAs that differentially expressed (M-bM-^IM-%1.5 fold-change) among preeclampsia placentas compared with matched controls. Up to 18,063 coding transcripts could be detected in placenta samples through 30,215 coding transcripts probes. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differential expressed lncRNAs and mRNAs. According to the GO-Pathway analysis of differential expressed lncRNAs/mRNAs, we choose three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, CEACAMP8 were evaluated by qPCR in 40 of preeclampsia placentas and 40 of controls. The results showed three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. Conclusions/Significance: Our study is the first one to determine genome-wide lncRNAs expression patterns in preeclampsia placenta by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which revealed that lncRNAs differentially expressed in preeclampsia placenta may exert a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, CEACAMP8 might be associated with preeclampsia. Taken together, this study may provide potential targets for future treatment of preeclampsia and novel insights into preeclampsia biology. LncRNAs/mRNAs profiles in 6 preeclampsia placentas and 5 matched normal pregnancy placentas tissues by microarray using Arraystar v2.0.
2013-09-12 | E-GEOD-50783 | biostudies-arrayexpress
Project description:Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. To identify potential A2BP1-dependent differential splicing events in ASD brain, we performed high-throughput RNA sequencing (RNA-Seq) on three autism samples with significant downregulation of A2BP1 (average fold change by quantitative RT-PCR = 5.9) and three control samples with average A2BP1 levels. The list of potential A2BP1-depending differential splicing events in ASD is given in the Supplementary file linked at the foot of this record.
2011-07-12 | E-GEOD-30573 | biostudies-arrayexpress
Project description:Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
2011-07-12 | GSE30573 | GEO
Project description:Context: Long non-coding RNAs (lncRNAs) regulate pathological processes, yet their potential roles in papillary thyroid carcinoma (PTC) are poorly understood. Objective: To profile transcriptionally dysregulated lncRNAs in PTC and identify lncRNAs associated with clinicopathological characteristics. We performed RNA sequencing of 12 paired PTC tumors and matched noncancerous tissues and correlated the expression of lncRNAs with clinical parameters.
2016-08-03 | E-GEOD-83520 | biostudies-arrayexpress
Project description:CoCl2 induced cytotoxicity is associated with dysregulated lncRNAs expression
| PRJNA473761 | ENA
Project description:To identify lncRNA expression in placentas from patients with late-onset preeclampsia (LOPE), we have employed whole genome microarray expression profiling as a discovery platform to identify differential expression of lncRNAs in placental samples from LOPE patients and normal controls. For microarray analysis, 8 randomly and blindly selected placental samples from LOPE patients and matched controls (4 samples per group) were used to extract total RNA. The expression profiles of the placental lncRNAs were detected using the Agilent Human lncRNA Microarray V4.0(OE Biotech, Shanghai, China). The threshold for a dysregulated lncRNA was set as a fold-change (FC) value of 2.0 or greater. A totle of 163 differentially expressed lncRNAs were identified. Expression of nine lncRNAs (NONHSAT145880, ENST00000587240, NONHSAT116812, NONHSAT104536, FR339600, NONHSAG018907, TCONS_l2_00014782, NONHSAT134432 and NONHSAG024318) from this microarray was quantified n placental tissues from the LOPE patients (n = 40) and controls (n = 35) delivered by caesarean section by real-time PCR, confirming low variability between the qRT-PCR results and the microarray data.
2017-04-18 | GSE97898 | GEO
Project description:A vast portion of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs) acting in the cytoplasm with largely unknown functions. Surprisingly, lncRNAs have been shown to interact with ribosomes, encode uncharacterized proteins, or act as ribosome sponges. These functions still remain mostly undetected and understudied owing to the lack of efficient tools for genome-wide simultaneous identification of ribosome-associated lncRNAs and peptide-producing lncRNAs. Here we present AHARIBO, a method for the detection of lncRNAs either untranslated, but associated with ribosomes, or encoding small peptides. Using AHARIBO in mouse embryonic stem cells during neuronal differentiation, we isolated ribosome-protected RNA fragments, translated RNAs and corresponding de novo synthesized polypeptides. Besides identifying mRNAs under active translation and associated ribosomes, we found and distinguished lncRNAs acting as ribosome sponges or encoding micropeptides, laying the ground for a better functional understanding of hundreds lncRNAs.
2021-09-09 | PXD022679 | Pride