Homo sapiens
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: phs000249.v1.p1
PROVIDER: PRJNA116889 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on DNA methylation, mRNA expression and microRNA (miRNA) expression in four distinct human brain regions. We show that brain tissues may be readily distinguished based on methylation status or expression profile. We find an abundance of genetic cis regulation mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249.v1.p1 Because of our interest in genomic regulation of expression and neurological disorders we embarked upon a series of experiments to provide a brain region-specific contextual framework for genetic and epigenetic regulation of gene expression. We obtained frozen brain tissue from the cerebellum, frontal cortex, pons and temporal cortex from 150 subjects (total 600 tissue samples). We undertook four separate assays across this series; first, genome-wide SNP genotyping; second, assay of >27,000 CpG methylation sites in each of the four brain regions; third, mRNA expression profiling of >22,000 transcripts in all four brain regions; and, fourth, miRNA expression profiling of 735 miRNA transcripts. Here we discuss the results of these experiments, particularly in the context of integrated datasets to define expression and CpG methylation quantitative trait loci (eQTL and methQTL) and detailing differences and similarities across brain regions.
2010-04-20 | E-GEOD-15745 | biostudies-arrayexpress
Project description:A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on DNA methylation and mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on methylation status or expression profile. We find an abundance of genetic cis regulation mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249 Because of our interest in genomic regulation of expression and neurological disorders we embarked upon a series of experiments to provide a brain region-specific contextual framework for genetic and epigenetic regulation of gene expression. We obtained frozen brain tissue from the cerebellum and frontal cortex from 318 subjects (total 724 tissue samples).
2012-05-08 | E-GEOD-36194 | biostudies-arrayexpress
Project description:A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on DNA methylation and mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on methylation status or expression profile. We find an abundance of genetic cis regulation mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249
2012-05-09 | GSE36194 | GEO
Project description:A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on DNA methylation, mRNA expression and microRNA (miRNA) expression in four distinct human brain regions. We show that brain tissues may be readily distinguished based on methylation status or expression profile. We find an abundance of genetic cis regulation mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249.v1.p1
2010-04-20 | GSE15745 | GEO
Project description:In this study, we investigated the interaction between CpG methylation and genetic polymorphisms by taking the advantage of the family structure in 22 nuclear pedigrees. We have identified CpG sites that exhibit heritable methylation patterns, among which the majority are SNPs ditrectly disrupting CpG dinucleotides. We also identified 27.2% of the heritable non-SNP CpGs were associated with cis-regulatory SNPs. Additionally, we have identified hundreds of CpG clusters whose the degree of DNA methylation variation is associated with genetic polymorphism. Investigate the influence of genetic variances on blood DNA methylation patterns in the human genome of 96 subjects from 22 pedigrees by using different approaches, including mid-parent offspring analysis (MPO), methylation quantitative trait loci (mQTL) analysis and allele-specific DNA methylation (ASM) Raw data not provided since the files contain genetic information of the human subject that should be protected.
2013-06-20 | E-GEOD-47614 | biostudies-arrayexpress
Project description:A large portion of common variant loci associated with genetic risk for schizophrenia reside within non-coding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci, based on co-localization of a risk SNP, eQTL and regulatory element sequence. These include physical interactions of non-contiguous gene-proximal and distal elements bypassing the linear genome, which was verified in prefrontal cortex and human induced pluripotent stem cell derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated non-coding SNPs and 3-dimensional genome architecture associated with chromosomal loopings and transcriptional regulation in the brain. Examination of H3K4me3 histone modifications in 3 samples.
2014-10-17 | E-GEOD-62391 | biostudies-arrayexpress
Project description:Previous studies in bulk tissue suggest that there are abundant expression quantitative trait loci (eQTLs) in human brain. This sample series is of cerebellar Purkinje cells isolated using laser capture microdissection from human cases without neurological disease but of known genotypes. These data may be helpful in confirming eQTLs in bulk tissue or in mapping other gene expression traits in an enriched neuronal population. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249
2013-01-01 | GSE37205 | GEO
Project description:Astrocytomas are common and lethal human brain tumors. Here, we have analyzed the methylation status of over 28,000 CpG islands and 18,000 promoters in normal human brain and in astrocytomas of various grades using the methylated-CpG island recovery assay (MIRA). We identified six to seven thousand methylated CpG islands in normal human brain. ~5% of the promoter-associated CpG islands in normal brain are methylated. Promoter CpG island methylation is inversely and intragenic methylation is directly correlated with gene expression levels in brain tissue. In astrocytomas, several hundred CpG islands undergo specific hypermethylation relative to normal brain with 428 methylation peaks common to more than 25% of the tumors. Genes involved in brain development and neuronal differentiation, such as POU4F3, GDNF, OTX2, NEFM, CNTN4, OTP, SIM1, FYN, EN1, CHAT, GSX2, NKX6-1, RAX, PAX6, DLX2, were strongly enriched among genes frequently methylated in tumors. There was an overrepresentation of homeobox genes and 31% of the most commonly methylated genes represent targets of the Polycomb complex. We identified several chromosomal loci in which many (sometimes more than 20) consecutive CpG islands were hypermethylated in tumors. Seven of such loci were near homeobox genes, including the HOXC and HOXD clusters, and the BARHL2, DLX1, and PITX2 genes. Two other clusters of hypermethylated islands were at sequences of recent gene duplication events. Our analysis offers mechanistic insights into brain neoplasia suggesting that methylation of genes involved in neuronal differentiation, perhaps in cooperation with other oncogenic events, may shift the balance from regulated differentiation towards gliomagenesis. Comparison of methylation patterns of 30 astrocytomas and 6 controls
2010-05-16 | E-GEOD-19391 | biostudies-arrayexpress
Project description:A large portion of common variant loci associated with genetic risk for schizophrenia reside within non-coding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci, based on co-localization of a risk SNP, eQTL and regulatory element sequence. These include physical interactions of non-contiguous gene-proximal and distal elements bypassing the linear genome, which was verified in prefrontal cortex and human induced pluripotent stem cell derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated non-coding SNPs and 3-dimensional genome architecture associated with chromosomal loopings and transcriptional regulation in the brain.
2014-10-17 | GSE62391 | GEO
Project description:Previous studies in bulk tissue suggest that there are abundant expression quantitative trait loci (eQTLs) in human brain. This sample series is of cerebellar Purkinje cells isolated using laser capture microdissection from human cases without neurological disease but of known genotypes. These data may be helpful in confirming eQTLs in bulk tissue or in mapping other gene expression traits in an enriched neuronal population. Authorized Access data: Mapping of GEO sample accessions to dbGaP subject/sample IDs is available through dbGaP Authorized Access, see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000249 The aim of this study was to examine gene expression in isolated purkinje cells from the human cerebellum. We obtained frozen brain tissue from the cerebellum. We stained sections with cresyl violet and separated Purkinje cells based on morphology and location within the cerebellum using laser capture microdissection. Expression analyses were then performed.
2013-01-01 | E-GEOD-37205 | biostudies-arrayexpress