Microglial RNA sequencing from humanized mouse model expressing schizophrenia susceptibility factor C4A
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ABSTRACT:
PROVIDER: PRJNA678711 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13067800_1.fastq.gz | Fastqsanger.gz | |||
| SRR13067800_2.fastq.gz | Fastqsanger.gz | |||
| SRR13067801_1.fastq.gz | Fastqsanger.gz | |||
| SRR13067801_2.fastq.gz | Fastqsanger.gz | |||
| SRR13067802_1.fastq.gz | Fastqsanger.gz |
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Project description:Human C4A gene locus is associated with increased schizophrenia risk. In order to investigate this genetic link, we constructed two mouse models that express human C4A or C4B, and one that overexpresses C4A. To investigate whether the isotypic effects of human-C4 gene is observed in the microglial transcriptional profile during adolescence in mice (postnatal day 40) in the medial prefrontal cortex, we conducted a bulk RNA sequencing of microglia. Our analyses showed no significant differentially expressed genes between any two groups.
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Project description:In the largest published genome-wide association study (GWAS) of schizophrenia to date (PGC1), the most significant association (P = 1.6 X 10-11) was observed at an intronic variant (rs1625579) within the MIR137 host gene (MIR137HG). In this study we have performed genome-wide RNA profiling of a human foetal neural progenitor cell line following miR-137 manipulation, in order to identify gene expression changes through which genetic variation at the MIR137HG locus could confer susceptibility to schizophrenia. Total RNA extracted from human neural progenitor cells manipulated with either mir137 inhibitor or mimic. 4 replicates per group. Genome wide transcript levels were then measured using gene expression microarrays.
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Project description:In the largest published genome-wide association study (GWAS) of schizophrenia to date (PGC1), the most significant association (P = 1.6 X 10-11) was observed at an intronic variant (rs1625579) within the MIR137 host gene (MIR137HG). In this study we have performed genome-wide RNA profiling of a human foetal neural progenitor cell line following miR-137 manipulation, in order to identify gene expression changes through which genetic variation at the MIR137HG locus could confer susceptibility to schizophrenia.
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Project description:Genome-wide association studies (GWAS) have accelerated the discovery of numerous genetic variants associated with schizophrenia. However, most risk variants show a small effect size (odds ratio (OR)<1.2), suggesting that more functional risk variants remain to be identified. Here, we employed region-based multi-marker analysis of genomic annotation (MAGMA) to identify additional risk loci containing variants with large OR value from Psychiatry Genomics Consortium (PGC2) schizophrenia GWAS data and then employed summary-data-based mendelian randomization (SMR) to prioritize schizophrenia susceptibility genes. The top-ranked susceptibility gene ATP5MD, encoding an ATP synthase membrane subunit, is observed to be downregulated in schizophrenia by the risk allele of CNNM2-rs1926032 in the schizophrenia-associated 10q24.32 locus.
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Project description:The molecular basis of complex neuropsychiatric disorders most likely involves many genes. In recent years, specific genetic variations influencing risk for schizophrenia and other neuropsychiatric disorders have been reported. We have used custom DNA microarrays and qPCR to investigate the expression of putative schizophrenia susceptibility genes and related genes of interest in the normal human brain. Expression of 31 genes was measured in Brodmann's area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18-67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse. Examination of expression across age allowed the identification of genes whose expression patterns correlate with age, as well as genes that share common expression patterns and that possibly participate in common cellular mechanisms related to the emergence of schizophrenia in early adult life. The expression of GRM3 and RGS4 decreased across the entire age range surveyed, while that of PRODH and DARPP-32 was shown to increase with age. NRG1, ERBB3, and NGFR show expression changes during the years of greatest risk for the development of schizophrenia. Expression of FEZ1, GAD1, and RGS4 showed especially high correlation with one another, in addition to the strongest mean levels of absolute correlation with all other genes studied here. Keywords: postmortem human brain collection Supplementary files: Gene expression measures in Matrix1379Normalized.txt include all data from the 1379 probes on the arrays, and are NOT adjusted for PMI, brain pH, and RIN, and are NOT averaged over multiple probes within genes. Raw data are located in Raw_1241842_gene_probe_profile.txt. We have used custom DNA microarrays to investigate gene expression in the normal human brain. Expression was measured in Brodmann's area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18-67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse.
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Project description:The molecular basis of complex neuropsychiatric disorders most likely involves many genes. In recent years, specific genetic variations influencing risk for schizophrenia and other neuropsychiatric disorders have been reported. We have used custom DNA microarrays and qPCR to investigate the expression of putative schizophrenia susceptibility genes and related genes of interest in the normal human brain. Expression of 31 genes was measured in Brodmann's area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18-67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse. Examination of expression across age allowed the identification of genes whose expression patterns correlate with age, as well as genes that share common expression patterns and that possibly participate in common cellular mechanisms related to the emergence of schizophrenia in early adult life. The expression of GRM3 and RGS4 decreased across the entire age range surveyed, while that of PRODH and DARPP-32 was shown to increase with age. NRG1, ERBB3, and NGFR show expression changes during the years of greatest risk for the development of schizophrenia. Expression of FEZ1, GAD1, and RGS4 showed especially high correlation with one another, in addition to the strongest mean levels of absolute correlation with all other genes studied here. Keywords: postmortem human brain collection Supplementary files: Gene expression measures in Matrix1379Normalized.txt include all data from the 1379 probes on the arrays, and are NOT adjusted for PMI, brain pH, and RIN, and are NOT averaged over multiple probes within genes. Raw data are located in Raw_1241842_gene_probe_profile.txt.
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Project description:The humanized mice's frontal cortical tissues were used for transcriptomic analysis, as this brain area shows early involvement in pathophysiology of schizophrenia. We transplanted hiPSC-astrocyte progenitors from one monozygotic twin pair discordant for schizophrenia and one healthy control into neonatal mouse forebrains and analyzed mouse behavior at five and ten months, followed by gene expression profiling of the frontal cortices seven days later.
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2014-10-11 | E-GEOD-62191 | biostudies-arrayexpress