RNA-seq of male and female control cortex
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76852 | GEO | 2016/02/23
SECONDARY ACCESSION(S): PRJNA308823
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: The goal of this study was to compare gene expression patterns in the male and female human cortex Methods: We performed RiboZero Gold (rRNA depleted) 50bp PE RNA-seq in a set of control samples of both sexes to identify sexually dimorphic gene expression patterns. Results: Within these samples, we corroborated findings from a discovery set of RNA-seq data from adult human cortex tissue from the BrainSpan consortium which demonstrated male-biased expression of astrocyte marker genes and a gene co-expression module found to be up-regulated in the adult autistic cortex. Conclusions: These findings suggest that sex-differential risk for autism spectrum disorder is not the result of sex-differential regulation of ASD risk genes, but of naturally occurring sexually dimorphic processes that modulate the impact of risk variants for autism spectrum disorder. 13 cerebral cortex samples from 10 individuals (7 samples from 5 males, 6 samples from 5 females). Three Samples are included in this study from Series GSE64018. **PLEASE NOTE: Raw data has been submitted to dbGAP**
2016-02-23 | E-GEOD-76852 | biostudies-arrayexpress
Project description:Sex estimation of human remains from demineralized blocks of tooth enamel by liquid chromatography tandem mass spectrometry (LC- MS/MS) and proteomic analysis of sexually dimorphic amelogenin peptides. The detection of the Y-isoform of amelogenin is used to estimate male sex. The combined signal intensity of the sexually dimorphic peptides from each samples of known sex is used to establish a statistical framework for the estimation of the female sex probability.
2018-11-29 | PXD009781 | Pride
Project description:Autism spectrum disorder (ASD) is a common, highly heritable neuro-developmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an etiologically 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/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 ASD brain. Moreover, using a published autism GWAS dataset, 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 etiology 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. Total RNA was extracted from approximately 100mg of postmortem brain tissue representing Cerebellum (C), Frontal cortex (F), and Temporal cortex (T), from autistic and control individuals.
2011-05-01 | E-GEOD-28521 | biostudies-arrayexpress
Project description:H3K27ac ChIP-seq were performed on postmortem samples from autism spectrum disorder and matched control brains. Tissues were chosen from three brain regions: prefrontal cortex, temporal cortex and cerebellum.
| EGAS00001001943 | EGA
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:In this study, we investigated the effects of prenatal bisphenol-A (BPA) exposure on transcriptome profiles in the frontal cortex of the rat offspring. Transcriptome profiling by RNA-seq analysis of frontal cortex tissues isolated from neonatal pups prenatally exposed to BPA revealed that a list of differentially expressed genes (DEGs) associated with autism spectrum disorder (ASD), including Ntng1, Auts2, and Ankrd11 was dysregulated in a sex-specific pattern. The gene ontology analysis revealed that the BPA-responsive genes in the offspring’s frontal cortex were significantly associated with ASD-related neurological functions. These results indicated that prenatal BPA exposure may increase the risk of ASD by impacting ASD-related genes in the offspring’s frontal cortex. We conducted experiments using the frontal cortex from neonatal pups prenatally exposed to BPA or vehicle control (BPA treament; pooled 3 pups frontal cortex, vehicle control; pooled 3 pups frontal cortex). 10-week-old female rats were daily treated with BPA at the concentration of 5,000 microgram/kilogram of maternal body weight or vehicle control from gestation day 1 (GD1) until parturition. Total RNAs were isolated and cDNAs were synthesized. The transcriptome profiles were performed using a high-throughtput RNA-seq.
2023-04-06 | GSE229073 | GEO
Project description:To investigate the effect of Grin2a (a schizophrenia risk gene) and Grin2b (an autism spectrum disorder risk gene) loss of function on brain transcriptome. We performed unbiased transcriptomic profiling (bulk RNAseq analysis) in 5 brain regions and at four postnatal ages in Grin2a and Grin2b mutant mice.
2023-08-31 | GSE218551 | GEO
Project description:Background: Autism spectrum disorder (ASD) is a severe early onset neurodevelopmental disorder with high heritability but significant heterogeneity. Traditional genome-wide approaches to test for association of common variants with autism susceptibility risk has met with limited success. However, novel methods to identify moderate risk alleles in attainable sample sizes are now gaining momentum. Methods:M-BM- In this study, we utilized publically available GWAS data from the Autism Genome Project (AGP) and annotated the results (p < 0.001) for eQTLs present in the parietal lobe, cerebellum, and lymphoblastoid cell lines. We then performed a test of enrichment by comparing these results to simulated data conditioned on minor allele frequency in order to generate an empirical p-value indicating statistically significant enrichment of eQTLs in top results from the autism GWAS. Results:M-BM- Our findings show a global enrichment of brain eQTLs, but not LCL eQTLs, among top SNPs from an autism GWAS. Additionally, the data implicates individual genesM-BM- SLC25A12,M-BM- PANX1M-BM- andM-BM- PANX2, as well as pathways previously implicated in autism. Conclusions:M-BM- These findings provide supportive rationale for the use of annotation-based approaches to GWAS. We use microarray technology to understand the etiology and pathology of psychiatric diseases at the transcriptomic level. Postmortem human brain samples came from the Stanley Medical Research InstituteM-bM-^@M-^Ys Neuropathology Consortium and Array collections, including schizophrenia, bipolar disorder and control samples.
2012-12-31 | E-GEOD-35974 | biostudies-arrayexpress
Project description:Background: Autism spectrum disorder (ASD) is a severe early onset neurodevelopmental disorder with high heritability but significant heterogeneity. Traditional genome-wide approaches to test for association of common variants with autism susceptibility risk has met with limited success. However, novel methods to identify moderate risk alleles in attainable sample sizes are now gaining momentum. Methods:M-BM- In this study, we utilized publically available GWAS data from the Autism Genome Project (AGP) and annotated the results (p < 0.001) for eQTLs present in the parietal lobe, cerebellum, and lymphoblastoid cell lines. We then performed a test of enrichment by comparing these results to simulated data conditioned on minor allele frequency in order to generate an empirical p-value indicating statistically significant enrichment of eQTLs in top results from the autism GWAS. Results:M-BM- Our findings show a global enrichment of brain eQTLs, but not LCL eQTLs, among top SNPs from an autism GWAS. Additionally, the data implicates individual genesM-BM- SLC25A12,M-BM- PANX1M-BM- andM-BM- PANX2, as well as pathways previously implicated in autism. Conclusions:M-BM- These findings provide supportive rationale for the use of annotation-based approaches to GWAS. We use microarray technology to understand the etiology and pathology of psychiatric diseases at the transcriptomic level. Postmortem human brain samples came from the Stanley Medical Research InstituteM-bM-^@M-^Ys Neuropathology Consortium and Array collections, including schizophrenia, bipolar disorder and control samples.
2012-12-31 | E-GEOD-35977 | biostudies-arrayexpress
Project description:Whole-exome sequencing studies have implicated chromatin modifiers and transcriptional regulators in autism spectrum disorder (ASD) through the identification of de novo loss of function mutations in affected individuals. Many of these genes are co-expressed in mid-fetal human cortex, suggesting ASD risk genes converge in regulatory networks that are perturbed in ASD during neurodevelopment. To elucidate such networks we mapped promoters and enhancers bound by the chromodomain helicase CHD8, which is strongly enriched in ASD-associated de novo loss of function mutations, using ChIP-seq in mid-fetal human brain, human neural stem cells (hNSCs), and embryonic mouse cortex. We find that CHD8 targets are strongly enriched for ASD risk genes that converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in significant dysregulation of ASD risk genes targeted by CHD8, as well as additional genes important for neurodevelopment, including members of the Wnt/M-NM-2-catenin signaling pathway. Integration of CHD8 binding data with genetic and gene co-expression data in ASD risk models provides support for additional ASD risk genes. Together, our results suggest that loss of CHD8 function contributes to ASD through regulatory perturbation of other ASD risk genes during human cortical development. Two biological replicates for each ChIP with appropriate Input control Four biological replicates for each condition in knockdown experiments (Ctrl construct, Chd8 target C, and Chd8 target G)
2015-01-21 | E-GEOD-57369 | biostudies-arrayexpress