Genome-wide DNA methylation profiling of human dorsolateral prefrontal cortex
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ABSTRACT: Reduced representation bisulfite sequencing (RRBS) was conducted on dorsolateral prefrontal cortex tissue samples taken from the brains of control individuals not affected by neurological disorder DNA methylation profiling was conducted using RRBS and the Illumina Genome Analyzer IIx
Project description:Reduced representation bisulfite sequencing (RRBS) was conducted on dorsolateral prefrontal cortex tissue samples taken from the brains of control individuals not affected by neurological disorder
Project description:Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder with a rising prevalence and genetic and environmental etiologies. Symptoms include deficits in social communication, repetitive patterns of behavior, and cognitive impairment. Neuroanatomic and biochemical investigations involve many brain areas with imbalance between glutamatergic and inhibitory neurotransmitters. We hypothesized that investigation of the synaptic compartment of the dorsolateral prefrontal cortex may provide proteomics signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractionation of the synaptoneurosomes from Brodmann area 9 of a well- characterized age- and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. healthy controls, were subjected to HPLC–tandem mass spectrometry and proteomic analysis.
Project description:The methylation status of colon epithelial cells was profiled in wild type mice and mice expressing a Dnmt3b transgene. Genome-scale methylation profiles were generated using reduced representation bisulfite sequencing (RRBS), with CpG methylation scored by promoter and also summarized by gene. Dnmt3b expression is associated with a strong increase in de novo methylation of a discrete subset of "methylation sensitive" genes which show a strong concordance with genes methylated in human colon cancer. These results, together with further analysis, indicate that colon epithelial cell methylation in the Dnmt3b mouse model predicts DNA methylation of human colon cancer with high confidence. Three each of Dnmt3b-induced and control mice, each split into two fractions.
Project description:Schizophrenia-associated anomalies in gene expression in postmortem brain are caused by a combination of genetic and environmental influences. Given the small effect size of common variants it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. However, at the gene level we will see more impact from common environmental risk factors mediated by influential epigenomic modifiers. In this study we examine changes in cortical gene expression to identify regulatory interactions and networks associated with the disorder. Gene expression analysis in post-mortem prefrontal dorsolateral cortex (BA 46) (n=74 matched pairs of schizophrenia, schizoaffective and control samples) was performed using Illumina HT12 gene expression microarrays. Significant gene interaction networks were identified for differentially expressed genes in pathways of neurodevelopmental and oligodendrocyte function.
Project description:The dorsolateral prefrontal cortex (DLPFC) is the association area in the anterior part of the frontal lobe and has a crucial role in cognitive functioning and negative symptoms in SZschizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n=20) and healthy individuals (n=20) followed by bioinformatic analysis to identify altered protein networks in SZ.
Project description:Alcohol use disorder (AUD) has a profound public health impact and understanding of the molecular mechanisms underlying the development and progression of AUD remain limited. Many genetic risk loci have been identified for AUD or alcohol consumption, though the neurobiological mechanisms underlying these loci remain largely unknown. DNA methylation (DNAm) differences between individuals with and without AUD can provide insight into the mechanisms that predispose to AUD and consequences of AUD itself. Here, we provide Illumina HumanMethylation EPIC array data generated in nucleus accumbens and dorsolateral prefrontal cortex, both addiction relevant brain tissues, from 119 decedents of European ancestry: 61 controls and 58 cases. From these data we have conducted an epigenome-wide association study (EWAS) and identified several CpG associations with AUD. A subset of the identified CpGs map to genes that were previoulsy identified as associated with substance use behaviors in genetic studies, but the other CpGs map to genes previoulsy unassociated with substance use behaviors and are novel.
Project description:Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC
Project description:We performed single-nucleus RNA sequencing of the dorsolateral prefrontal cortex from 15 normal, pathological aging, and Alzheimer’s disease human brains that varied by APOE and TREM2 genotype to analyze cell-type specific transcriptomic changes across the range of Alzheimer’s disease pathology and genetic risk factors.