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Functional annotation of genes differentially expressed between primary motor and prefrontal association cortices of macaque brain

ABSTRACT: DNA microarray-based genome-wide transcriptional profiling and gene network analyses were used to characterize the molecular underpinnings of the frontal neocortical organization in rhesus macaque, with particular focus on the differences in the functional annotation of genes in the primary motor cortex and the prefrontal association cortex. Biofunctional analysis of the differentially expressed genes showed that the list of genes selectively expressed in the primary motor cortex were enriched with genes involved in development, oligodendrocyte function, and increased energy consumption, whereas the list of genes selectively expressed in the prefrontal association cortex were enriched with genes involved in cell morphology and calcium dynamics. These functional differences in selectively expressed genes may reflect the fundamental molecular structure of each cortex.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE37997 | GEO | 2012/10/01

SECONDARY ACCESSION(S): PRJNA167032

REPOSITORIES: GEO

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Project description:DNA microarray-based genome-wide transcriptional profiling and gene network analyses were used to characterize the molecular underpinnings of the frontal neocortical organization in rhesus macaque, with particular focus on the differences in the functional annotation of genes in the primary motor cortex and the prefrontal association cortex. Biofunctional analysis of the differentially expressed genes showed that the list of genes selectively expressed in the primary motor cortex were enriched with genes involved in development, oligodendrocyte function, and increased energy consumption, whereas the list of genes selectively expressed in the prefrontal association cortex were enriched with genes involved in cell morphology and calcium dynamics. These functional differences in selectively expressed genes may reflect the fundamental molecular structure of each cortex. Brain tissue was obtained from 4 adolescent rhesus monkeys (Macaca mulatta) aged between 2.6 and 2.7 years that had been bred in group cages without being subjected to any experimental treatment. Adequate measures were taken to minimize pain and discomfort, in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 80M-bM-^@M-^S23). The monkeys were perfused with 500M-bM-^@M-^S1000 ml of ice-cold saline containing heparin sodium (1000 U/ml, Novo Heparin; Leo Pharmaceutical Products, Ballerup, Denmark) through the ascending aorta within 15 min of an overdose injection of pentobarbital sodium (50 mg/kg, i.p., Somnopentyl; Kyoritsu Shoji, Tokyo, Japan). The 2 neocortical areas (M1 and A46) were identified by sulcal landmarks. We used the forelimb region of M1 for the present analysis, which is located around the superior genu of the central sulcus. A46 was obtained from both the upper and lower banks of the principal sulcus. Each area from the left hemispheres was dissected on crushed ice and immediately frozen in liquid nitrogen.

Project description:Anorexia nervosa (AN), bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) are complex psychiatric disorders with shared obsessive features, thought to arise from the interaction of multiple genes of small effect with environmental factors. Potential candidate genes for AN, BN, and OCD have been identified through clinical association and neuroimaging studies; however, recent genome-wide association studies of eating disorders (ED) so far have failed to report significant findings. Additionally, few if any studies have interrogated postmortem brain tissue for evidence of eQTLs associated with candidate genes, which has particular promise as an approach to elucidating molecular mechanisms of association. We therefore selected single nucleotide polymorphisms (SNPs) based on candidate gene studies for AN, BN, and OCD from the literature, and examined the association of these SNPs with gene expression across the lifespan in prefrontal cortex of a non-psychiatric control cohort (N=268). Several risk-predisposing SNPs were significantly associated with gene expression among control subjects. We then measured gene expression in the prefrontal cortex of cases previously diagnosed with obsessive psychiatric disorders, e.g., eating disorders (ED; N=15), and obsessive-compulsive disorder/obsessive-compulsive personality disorder or tics (OCD/OCPD/Tic; N=16), and non-psychiatric controls (N=102) and identified 6 and 286 genes that were differentially expressed between ED compared to controls and OCD cases compared to controls, respectively (FDR < 5%). However, none of the clinical risk SNPs were among the eQTLs and none were significantly associated with gene expression within the broad obsessive cohort, suggesting larger sample sizes or other brain regions may be required to identify candidate molecular mechanisms of clinical association in postmortem brain datasets. Gene expression data from the dorsolateral prefrontal cortex (DLPFC) from postmortem tissue on 133 subjects - 15 eating disorder (ED) patients, 16 obessive compulsive disorder (OCD) patients, and 102 non-psychiatric controls - run on the Illumina HumanHT-12 v3 microarray

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Functional annotation of genes differentially expressed between primary motor and prefrontal association cortices of macaque brain

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