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E-PROT-52

ABSTRACT: Protein expression in the dorsolateral prefrontal cortex of normal brain samples from the Johns Hopkins and Baltimore Coroner Aging Arm of Consensus Brain Proteomics Study

PROVIDER: E-PROT-52 | ExpressionAtlas | 2021-05-20

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-PROT-52-analysis-methods.tsv	Tabular
	E-PROT-52-configuration.xml	Xml
	E-PROT-52-factors.xml	Xml
	E-PROT-52-raw-counts-MappedToGeneID.tsv	Tabular
	E-PROT-52-raw-counts-MappedToGeneID.txt	Txt

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Project description:Protein expression in the dorsolateral prefrontal cortex brain samples from the Baltimore Longitudinal Study of Aging (BLSA)

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Project description:Differences in transcript splicing are well documented among tissues and between sexes in humans and other organisms. Further, splicing changes in selected genes have been reported in human and mouse brain development. Using high-throughput RNA sequencing we characterized the transcriptome-wide splicing changes occurring over the lifespan in the human brain. We found that in two brain regions, prefrontal cortex and cerebellum, as many as 37% of all expressed protein-coding multi-exon genes undergo significant splicing changes between birth and 98 years of age. Approximately 40% of these changes take place in aging. We confirmed our findings using exon arrays and PCRs and detected identified splicing changes at the protein level. We further associated distinct patterns of age-related splicing changes with expression of the corresponding splicing factors. Thus, splicing plays an important role in shaping the human brain transcriptome in both development and aging. Human post-mortem brain samples from prefrontal cortex and cerebellum from 30 individuals with ages from birth to 100 years were collected. For each five individuals of similar age RNA, extracted from dissected tissue, was pooled resulting in 5 pooled samples. Obtained RNA was hybridized with Affymetrix Human Exon 1.0 ST arrays.

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Project description:Protein expression in the dorsolateral prefrontal cortex of normal, Alzheimer's and Asymptomatic Alzheimer's disease brain samples from the Banner Sun Health Research Institute collection

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Temporal Dynamics and Genetic Control of Transcription in the Human Prefrontal Cortex

Project description:In order to gain a global molecular perspective on how the human genome gives rise to the brain, we explore the temporal dynamics and genetic control of transcription in human dorsolateral prefrontal cortex in an extensive series of brain tissue from fetal development through aging. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half century later in life, this phenomenon is mirrored in aging as well as neurodegeneration. While we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire dataset is freely available (GEO). RNA from 269 human prefrontal cortex samples ranging from fetal development (negative ages) through aging (80 years) were analyzed on custom 2-color microarrays from the National Human Genome Research Institute (NHGRI) microarray core facility using a reference RNA comprised of a pool of all samples. SNP genotype data for these subjects can be found in dbGAP under Study ID *phs000417.v1.p1* http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000417.v1.p1 Both the gene expression and SNP data from this study can be interrogated gene-by-gene with a biologist-friendly stand-alone application available at http://www.libd.org/braincloud . The original publication of this data appeared in the Oct. 27th 2011 volume of Nature: http://www.nature.com/nature/journal/v478/n7370/full/nature10524.html .

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