Prefrontal cortex gene expression signature in autistic BTBR mice
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE87601 | GEO | 2016/10/05
SECONDARY ACCESSION(S): PRJNA345353
REPOSITORIES: GEO
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Project description:Autism spectrum disorders (ASD) are characterized by a high degree of genetic heterogeneity. Genomic studies identified common pathological processes underlying the heterogeneous clinical manifestations of ASD, and transcriptome analyses revealed that gene networks involved in synapse development, neuronal activity and immune function are deregulated in ASD. Mouse models provide unique tools to investigate the neurobiological basis of ASD. Here we used the BTBR (BTBR T+ Itpr3tf/J) ASD mouse model to identify conserved ASD-related molecular signatures. Gene expression in the BTBR mouse prefrontal cortex was measured by microarrays and compared to the gene expression profile of C57Bl6/J controls (5 months old, n= 3 mice per group).
2016-05-18 | E-GEOD-81502 | biostudies-arrayexpress
Project description:Autism spectrum disorders (ASD) are characterized by a high degree of genetic heterogeneity. Genomic studies identified common pathological processes underlying the heterogeneous clinical manifestations of ASD, and transcriptome analyses revealed that gene networks involved in synapse development, neuronal activity and immune function are deregulated in ASD. Mouse models provide unique tools to investigate the neurobiological basis of ASD. Here we used the BTBR (BTBR T+ Itpr3tf/J) ASD mouse model to identify conserved ASD-related molecular signatures.
2016-05-18 | GSE81502 | GEO
Project description:Autism spectrum disorders (ASD) are characterized by a high degree of genetic heterogeneity. Genomic studies identified common pathological processes underlying the heterogeneous clinical manifestations of ASD, and transcriptome analyses revealed that gene networks involved in synapse development, neuronal activity and immune function are deregulated in ASD. Mouse models provide unique tools to investigate the neurobiological basis of ASD. Here we used the BTBR (BTBR T+ Itpr3tf/J) ASD mouse model to identify conserved ASD-related molecular signatures. Gene expression in the BTBR mouse hippocampus was measured by microarrays and compared to the gene expression profile of C57Bl6/J controls (5 months old, n= 4 mice per group).
2016-05-18 | E-GEOD-81501 | biostudies-arrayexpress
Project description:Autism spectrum disorders (ASD) are characterized by a high degree of genetic heterogeneity. Genomic studies identified common pathological processes underlying the heterogeneous clinical manifestations of ASD, and transcriptome analyses revealed that gene networks involved in synapse development, neuronal activity and immune function are deregulated in ASD. Mouse models provide unique tools to investigate the neurobiological basis of ASD. Here we used the BTBR (BTBR T+ Itpr3tf/J) ASD mouse model to identify conserved ASD-related molecular signatures.
2016-05-18 | GSE81501 | GEO
Project description:Purpose: The goal of this study was to assess the status of splicing changes in microexons in the cortex of individuals with autism. Methods: We performed RiboZero Gold (rRNA depleted) 50bp PE RNA-seq in a larger set of case and control samples to define 12 autism and 12 control samples showing the greatest global differential gene expression change. These samples, which show differential expression of the splicing regulator SRRM4, were used to evaluate global splicing changes. Results: Within these samples, 126 of 504 (30%) detected alternative microexons display a mean ?PSI > 10 between ASD and control subjects of which 113 (90%) also display neural-differential regulation. By contrast, only 825 of 15,405 (5.4%) longer (i.e. >27 nt) exons show such misregulation, of which 285 (35%) correspond to neural-regulated exons. Notably, we also observe significantly higher correlations between microexon inclusion and nSR100 mRNA expression levels across the stratified ASD samples and controls, for those microexons regulated by nSR100 relative to those microexons that are not regulated by this factor (p=1.4×10-7, Wilcoxon Sum Rank test). Conclusions: These data suggest microexon regulation is a potentially important mechanism underlying ASD and likely other neurodevelopmental disorders 12 case samples representing a more extreme autism gene expression signature and 12 representative controls; raw data have been submitted to dbGaP
2014-12-09 | E-GEOD-64018 | biostudies-arrayexpress
Project description:Mouse line BTBR T+ Iptr3tf/J (hereafter referred as to BTBR/J) is a congenic mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (hereafter referred to as B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (RIKEN BioResource Research Center; RBRC, Tsukuba, Japan; RBRC ID: 01206, hereafter referred to as BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. Our results identified the transcriptome profiling in BTBR/R mice compared to B6 mice, which could contribute to the understanding of ASD molecular pathology as well as the differences in sociality observed between BTBR/J mice and B6 mice.
2020-11-19 | GSE156646 | GEO
Project description:Purpose: The goal of this study was to assess the status of splicing changes in microexons in the cortex of individuals with autism. Methods: We performed RiboZero Gold (rRNA depleted) 50bp PE RNA-seq in a larger set of case and control samples to define 12 autism and 12 control samples showing the greatest global differential gene expression change. These samples, which show differential expression of the splicing regulator SRRM4, were used to evaluate global splicing changes. Results: Within these samples, 126 of 504 (30%) detected alternative microexons display a mean ΔPSI > 10 between ASD and control subjects of which 113 (90%) also display neural-differential regulation. By contrast, only 825 of 15,405 (5.4%) longer (i.e. >27 nt) exons show such misregulation, of which 285 (35%) correspond to neural-regulated exons. Notably, we also observe significantly higher correlations between microexon inclusion and nSR100 mRNA expression levels across the stratified ASD samples and controls, for those microexons regulated by nSR100 relative to those microexons that are not regulated by this factor (p=1.4×10-7, Wilcoxon Sum Rank test). Conclusions: These data suggest microexon regulation is a potentially important mechanism underlying ASD and likely other neurodevelopmental disorders
2014-12-09 | GSE64018 | GEO
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:The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC). The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1) and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b). Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1) and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of genetic alterations in OGG1 in pathogenesis of autism. Gene expression profiles in the cerebellum of 8 weeks old BTBR T+tf/J mice that exhibit an autism-like behavioral phenotype and control C57BL/6J mice were examined using high-throughput Agilent whole genome 8x60K mouse microarrays.
2014-10-23 | E-GEOD-62594 | biostudies-arrayexpress
Project description:Autism spectrum disorder (ASD) affects these core domains: ritualistic-repetitive behaviors, impaired social interaction, and deficits in non-verbal communication/language development. Although ASD is heritable, its extreme heterogeneity defies genetic analyses. A number of ASD susceptibility genes have been identified. The Lebanese population is ideal for uncovering recessive genes because of a high rate of shared ancestry, consanguineous marriages, and high number of offspring per family. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33). Cytogenetics 2.7M Microarrays/CytoScan⢠HD arrays allowed mapping of homozygous regions of the genome.
2017-07-24 | E-MTAB-4963 | biostudies-arrayexpress