Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. Prefrontal cortex (PFC) and cerebellum samples were obtained from 46 brains archived in the London Brain Bank for Neurodegenerative Disorders (LBBND). Of these 22 were schizophrenia cases, ands of the cases 12 were male.
Project description:To understand the roles of molecules in functional differentiation among adult human tissues, we performed a systematic survey of mRNA, protein, and protein phosphorylation as well as miRNA expression, in three tissues: cerebellum, prefrontal cortex and liver. We found that tissues were clearly distinct from one another at all levels. Furthermore, our results showed that miRNA differently expressed between tissues have significant, but modest effect on expression of mRNA and somewhat stronger effect on expression of proteins among the tissues. Notably, miRNA preferentially targeted gene regulators, transcription factors and kinases, in all three tissues studied. Following this path, we found that miRNA effect was further amplified through expression changes of target transcription factors and kinases, leading to further changes in their targets’ expression and phosphorylation levels. Importantly, miRNA regulation leads to reduced, rather than increased gene expression variation among individuals between two brain regions. These observations uncover the complexity of miRNA regulatory interactions and are compatible with suggested role of miRNA in gene expression canalization. Adult human post-mortem tissue samples: cerebellum, prefrontal cortex and liver, were collected. Each tissue contains three individuals totalling 9 samples in this datasets. RNA extracted from these dissected tissue was hybridized to Agilent Human miRNA Microarray.
Project description:To understand the roles of molecules in functional differentiation among adult human tissues, we performed a systematic survey of mRNA, protein, and protein phosphorylation as well as miRNA expression, in three tissues: cerebellum, prefrontal cortex and liver. We found that tissues were clearly distinct from one another at all levels. Furthermore, our results showed that miRNA differently expressed between tissues have significant, but modest effect on expression of mRNA and somewhat stronger effect on expression of proteins among the tissues. Notably, miRNA preferentially targeted gene regulators, transcription factors and kinases, in all three tissues studied. Following this path, we found that miRNA effect was further amplified through expression changes of target transcription factors and kinases, leading to further changes in their targetsM-bM-^@M-^Y expression and phosphorylation levels. Importantly, miRNA regulation leads to reduced, rather than increased gene expression variation among individuals between two brain regions. These observations uncover the complexity of miRNA regulatory interactions and are compatible with suggested role of miRNA in gene expression canalization. Adult human post-mortem tissue samples: cerebellum, prefrontal cortex and liver, were collected. Each tissue contains three individuals totalling 9 samples in this datasets. RNA extracted from these dissected tissue was hybridized to Affymetrix Human Exon 1.0 ST arrays.
Project description:This SuperSeries is composed of the following subset Series: GSE17757: Gene expression data from primate postnatal brain in prefrontal cortex: time course GSE18012: miRNA expression data from human postnatal brain in prefrontal cortex: time course GSE18013: miRNA expression data from rhesus macaque postnatal brain in prefrontal cortex: time course Refer to individual Series
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.
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)
Project description:Genome-wide prefrontal cortex and cerebellum DNA methylation profiles of younger and older adult humans, captive chimpanzees, and captive rhesus macaques
Project description:DNA methylation data from Papio hamadryas (baboons) profiled on the mammalian methylation array (HorvathMammalMethylChip40) which focuses on highly conserved CpGs across mammalian species. Seven tissue types (fetal cerebral cortex, adult cerebral cortex, cerebellum, adipose, heart, liver, and skeletal muscle) with ages ranging from late fetal life to 22.8 years of age.
Project description:This laboratory studies the role of carbohydrates in the development of the central nervous system. Comparison of glycosyltransferase gene expression in developing rodent cerebellum with the aim of understanding the regulation of tissue-specific glycans RNA from adult and postnatal day 7 BALB/c mouse cerebellum was extracted and analyzed for differences in glycosyltransferase expression. Three replicate samples were processed for each age group and hybridized to the GLYCOv2 array.