Genomics

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BrainCloud: Data from human postmortem brain procurement for the neuropathology section


ABSTRACT:

This study explores the temporal dynamics and genetic control of transcription and DNA methylation in the human dorsolateral prefrontal cortex in postmortem tissue. This study examines 269 subjects for gene expression (version 1) and 108 subjects for DNA methylation (version 2). The subjects are normal controls without neuropathological and neuropsychiatric diagnosis and range in age from fetal weeks 14-20 through old age (>80). We discover fast changes in gene expression occurring during early brain development. Later in life, the changes are considerably slower. Many genes reverse pattern of expression between fetal and early postnatal development. We identify thousands of strong associations of SNPs with gene expression. We examine DNA methylation in ~14,500 genes at ~27,000 CpG loci focused on 5' promoter regions. The fastest changes in DNA methylation also occur during the prenatal period, slow down markedly after birth and continue to slow further with aging. DNA methylation is strongly associated with genotypic variants and correlates with expression of a subset of genes. DNA for genotyping was obtained from the cerebella and applied to either Illumina 650K or 1 million BeadArrays - only genotypes common to both platforms are analyzed here. Genotypes were called using BeadExpress software. Doi: 10.1038/nature10524 Nature, 478:519-524, 2011; doi:10.1016/j.ajhg.2011.12.020, AJHG 90, 1-13, Feb 10, 2012. The methylation data can be downloaded at: BrainCloud.

OTHER RELATED OMICS DATASETS IN: PRJNA143735

PROVIDER: phs000417.v2.p1 | EGA |

REPOSITORIES: EGA

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Publications


Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression change  ...[more]

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