Similar Datasets
Project description:Knockdown of ASD risk genes leads to a shared transcriptional signature
| PRJNA797092 | ENA
Project description:Austism spectrum disorder (ASD) is a heterogeneous behavioral disease most commonly characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a common clinical outcome. Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA/lentivirus constructs. Whole genome expression analysis was conducted for each of the knock-down cultures as well as a mock-transduced culture and a culture exposed to a lentivirus expressing luciferase. Gene set enrichment and a causal reasoning engine were employed to indentify pathway level perturbations generated by the transcript knock-down. Quantitation of the shRNA targets confirmed the successful knock-down at the transcript and protein levels of at least 75% for each of the genes. After subtracting out potential artifacts caused by transfection and viral infection, gene set enrichment and causal reasoning engine analysis showed that a significant number of gene expression changes mapped to pathways associated with neurogenesis, long-term potentiation, and synaptic activity. This work demonstrates that despite the complex genetic nature of ASD, there are common molecular mechanisms that connect many of the best established autism candidate genes. By identifying the key regulatory checkpoints in the interlinking transcriptional networks underlying autism, we are better able to discover the ideal points of intervention that provide the broadest efficacy across the diverse population of autism patients. n=4 per group. Luciferase shRNA used as control group for shRNA to various gene targets.
2013-05-23 | E-GEOD-47150 | biostudies-arrayexpress
Project description:DNA from ectodermal cells of individuals with an Autism Spectrum Disorder born to mothers aged 35 and older was analzyed for discovery of differentially methylated regions and comethylation modules associated with ASD DNA from 48 individuals with ASD and DNA from 48 typically developing controls (all born to mothers older than 35) was isolated, bisulphite converte, and hybridized to the Illumina 450K array.
2014-05-05 | E-GEOD-50759 | biostudies-arrayexpress
Project description:DNA from ectodermal cells of individuals with an Autism Spectrum Disorder born to mothers aged 35 and older was analzyed for discovery of differentially methylated regions and comethylation modules associated with ASD
2014-05-05 | GSE50759 | GEO
Project description:Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
| PRJEB31117 | ENA
Project description:Austism spectrum disorder (ASD) is a heterogeneous behavioral disease most commonly characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a common clinical outcome. Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA/lentivirus constructs. Whole genome expression analysis was conducted for each of the knock-down cultures as well as a mock-transduced culture and a culture exposed to a lentivirus expressing luciferase. Gene set enrichment and a causal reasoning engine were employed to indentify pathway level perturbations generated by the transcript knock-down. Quantitation of the shRNA targets confirmed the successful knock-down at the transcript and protein levels of at least 75% for each of the genes. After subtracting out potential artifacts caused by transfection and viral infection, gene set enrichment and causal reasoning engine analysis showed that a significant number of gene expression changes mapped to pathways associated with neurogenesis, long-term potentiation, and synaptic activity. This work demonstrates that despite the complex genetic nature of ASD, there are common molecular mechanisms that connect many of the best established autism candidate genes. By identifying the key regulatory checkpoints in the interlinking transcriptional networks underlying autism, we are better able to discover the ideal points of intervention that provide the broadest efficacy across the diverse population of autism patients.
2013-05-23 | GSE47150 | GEO
Project description:Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are highly heterogeneous conditions with strong genetic underpinnings. Among the numerous risk genes implicated in NDDs, DEAF1 has emerged as a key candidate, with pathogenic variants linked to ASD and DEAF1-associated neurodevelopmental disorder (DAND). However, its precise role in human neurodevelopment remains poorly understood. Human cortical organoids (hCOs) provide a physiologically relevant model that retains the authentic human genetic background, faithfully recapitulating fetal brain development while minimizing extrapolation errors associated with genetic variability. In this study, we investigate the role of DEAF1 in neurodevelopment and its implications for NDDs using hCOs. We demonstrate that DEAF1 mutations disrupt chromatin accessibility at neuronal gene loci in human embryonic stem cells (hESCs), leading to significant transcriptional alterations.
2026-03-17 | GSE304228 | GEO
Project description:Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with = 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. Keywords: Autism spectrum disorder, Affymetrix SNP genotyping, linkage analysis, copy number analysis, chromosomal rearrangements.
2007-02-20 | GSE6754 | GEO
Project description:Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by abnormalities in reciprocal social interactions and language development and/or usage, and by restricted interests and repetitive behaviors. Differential gene expression of neurologically relevant genes in lymphoblastoid cell lines from monozygotic twins discordant in diagnosis or severity of autism suggested that epigenetic factors such as DNA methylation or microRNAs (miRNAs) may be involved in ASD. The goal of this study was to reveal dysregulation in miRNA levels that are inversely correlated with altered levels of target genes that, in turn, may be associated with the underlying pathophysiology of ASD, and to provide a better understanding of the role of miRNAs as a post-transcriptional gene regulatory mechanism associated with ASD. Lymphoblastoid cell lines (LCLs) derived from peripheral lymphocytes of 14 male subjects were obtained from the Autism Genetic Resource Exchange (AGRE, Los Angeles, CA). The subjects included three pairs of monozygotic twins discordant for diagnosis of autism, a normal sibling for 2 of the twin pairs, two pairs of autistic and unaffected siblings, and a pair of normal monozygotic twins. Global miRNA expression profiling of these LCLs was performed using high-throughput miRNA microarray analysis. A reference design was used for microarray hybridization in this study. The sample miRNAs were coupled with Cy3, whereas the common reference miRNA was coupled with Cy5, and two-colored miRNA microarray analyses were carried out by cohybridizing an equal amount of both miRNA samples onto one slide. Selected differentially expressed miRNAs were confirmed by quantitative RT-PCR, and the putative target genes of two of the confirmed miRNAs were validated by knockdown and overexpression of the respective miRNAs.
2010-04-09 | E-GEOD-21086 | biostudies-arrayexpress
Project description:This study identifies conserved protein biomarkers for Autism Spectrum Disorder (ASD) using a cross-species proteomic approach. Proteomic analyses were conducted on serum and brain samples from CNTNAP2 knockout (KO) mice and human ASD patient serum. A total of 132 conserved proteins were identified, with functional enrichment in lipid metabolism, synaptic signaling, and immune response. Machine learning refined these to ten key proteins demonstrating high classification performance. This dataset supports the discovery of ASD biomarkers with potential clinical applications.
2026-02-23 | PXD060810 | Pride