Systematic analysis of gene expression in human brains before and after death.
Author(s): Franz H, Ullmann C, Becker A, Ryan M, Bahn S, Arendt T, Simon M, Pääbo S, Khaitovich P
Publication: Genome Biol, 2005, Vol. 6, Page R112
PubMed ID: 16420671 PubMed Review Paper? No
Purpose of Paper
The purpose of this paper was to compare gene expression between surgically resected and autopsy specimens and between brain regions using specimens from the hippocampus and frontal cortex.
Conclusion of Paper
Of the 42,427 detected transcripts, 13.4% were differentially expressed between surgical resection and autopsy specimens, and 15.5% were differentially expressed between frontal cortex and hippocampus specimens. Of the differentially expressed transcripts, the majority were differentially expressed between autopsy and surgical resection specimens in both hippocampus and frontal cortex, although 2.6% were differentially expressed between autopsy and surgical specimens in a brain region-dependent manner. Importantly, while 11 of the 12 surgical specimens came from patients with epilepsy, none of the identified genes were differentially expressed between surgical and autopsy specimens were found to be affected by epilepsy. Genes with higher expression in autopsy specimens were those involved in the ubiquitin cycle and protein ubiquitination and genes with lower expression in autopsy specimens than surgical resection specimens included those involved in protein biosynthesis, rRNA processing, organelle organization and biogenesis and induction of apoptosis. Using published data from an additional 40 postmortem brains, the authors report that the transcripts differentially expressed between surgical and autopsy specimens did not show more variation in expression than other transcripts, nor were they more correlated with post-mortem interval (PMI).
Studies
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Study Purpose
The purpose of this study was to compare gene expression in surgical resection and autopsy hippocampus and frontal cortex specimens. Non-tumorous hippocampus specimens were collected from 5 patients undergoing surgery for epilepsy due to anaplastisches Oligo WHO III (1 patient), glioblastoma (2 patients), Ammon's horn sclerosis (1 patient), or ganglioglioma (1 patient), one patient undergoing surgery for Atpisches Meningeom Grad II, and upon autopsy from 4 individuals with no known neurological conditions (PMI unspecified). Additionally, frontal cortex specimens were obtained from 6 epileptic patients with focal cortical dysplasia, and 6 autopsy specimens with no neurological conditions (PMI unspecified). Specimens were stored at -80˚C until RNA extraction using Trizol, followed by purification using RNEasy. Expression was determined by hybridization to Affymetrix HG-U133plus2 arrays. Gene expression data from 40 postmortem brains (details of handling were not specified) was used to investigate expression variability and effects of PMI.
Summary of Findings:
Of the 42,427 detected transcripts, 5,703 (13.4%) were differentially expressed between surgical resection and autopsy specimens, with afalse discovery rate <0.01. Of these 5,703 differentially expressed transcripts, 4,508 were differentially expressed between autopsy and surgical resection specimens in both hippocampus and frontal cortex specimens, 981 were differentially expressed between brain regions and between autopsy and surgical specimens, and 214 were differentially expressed between autopsy and surgical specimens in a brain region-dependent manner. Although, 11 of 12 surgical specimens were obtained from patients with epilepsy, none of the genes identified to be differentially expressed between surgical and autopsy specimens were found to be associated with epilepsy. Further, genes previously found to be associated with epilepsy were not over-represented on the list of differentially expressed transcripts. Additionally, results obtained when the surgical specimen from the patient without epilepsy was included in the sample set were very strongly correlated with those obtained when specimens from that patient were excluded (r=0.948, p<10-15). The 4508 transcripts differentially expressed between surgical and autopsy specimens represented all three gene ontology classifications: biological process, molecular function and cellular component. Among the transcripts with higher expression in autopsy specimens were those involved in the ubiquitin cycle and protein ubiquitination, while transcripts with lower expression in autopsy specimens than surgical resection specimens included those involved in protein biosynthesis, rRNA processing, organelle organization and biogenesis and induction of apoptosis. Using published data from an additional 40 postmortem brains, the authors report that the transcripts differentially expressed between surgical and autopsy specimens did not display any more variation in expression levels than other transcripts, nor were they more strongly correlated with PMI.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Epilepsy
- Not specified
- Autopsy
- Neoplastic - Other
Platform:
Analyte Technology Platform RNA DNA microarray Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Biospecimen location Hippocampus
Frontal cortex
Preaquisition Postmortem interval Unspecified range of PMI
Preaquisition Surgical procedure type Autopsy
Surgical resection
Preaquisition Diagnosis/ patient condition Post-mortem
Epilepsy
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Study Purpose
The purpose of this study was to compare gene expression profiles between specimens from the hippocampus and frontal cortex. Non-tumorous hippocampus specimens were collected from 5 patients undergoing surgery for epilepsy due to anaplastisches oligo WHO III (1 patient), glioblastoma (2 patients), Ammon's horn sclerosis (1 patient), or ganglioglioma (1 patient), and one patient undergoing surgery for Atpisches Meningeom Grad II, and upon autopsy from 4 individuals with no known neurological conditions (PMI unspecified). Specimens from the frontal cortex were obtained from 6 epileptic patients with focal cortical dysplasia, and from 6 individuals with no known neurological conditions after a sudden death (PMI unspecified). Specimens were stored at -80˚C until RNA using Trizol followed by purification using RNEasy.
Summary of Findings:
Of the 42,427 detected transcripts, 6,568 (15.5%) were differentially expressed between hippocampus and frontal cortex specimens. Statistical significance of differences in transcript levels between brain regions was dependent on whether the specimen was procured during surgery or autopsy for only 234 of the 6,568 transcripts, indicating expression differences among brain regions are not profoundly affected by death. Although, 874 genes were found to be differentially expressed between frontal cortex and hippocampus specimens procured during autopsy, 6,699 transcripts were differentially expressed between frontal cortex and hippocampus specimens procured during surgery. Despite the large disparity in the number of differentially expressed transcripts, differences in transcript levels between specimens from the hippocampus and frontal cortex were strongly correlated among surgical and autopsy specimens (R=0.763 , p<10-15).
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Autopsy
- Neoplastic - Benign
- Epilepsy
Platform:
Analyte Technology Platform RNA Real-time qRT-PCR Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Biospecimen location Hippocampus
Frontal cortex
Preaquisition Surgical procedure type Autopsy
Surgical resection
Preaquisition Diagnosis/ patient condition Post-mortem
Epilepsy