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Probe level meta analysis of microarray data to understand the role of retrotransposable elements in myelination.

ABSTRACT: This study aim to understand the role of retrotransposable elements in myelination Raw data with accession number GSE11218 and GSE5940 (using Affymetrix expresion GeneChIP Rat Genome 230 2.0 and 230A, respectively) were extracted fromm GEO. Probe level information was extracted using R library rat2302probe (for Rat genome 230 2.0) and rae230aprobe (for rat genome 230A). Unique probe sequence in 230 2.0 and 230A platform were retained and the intersect probes (90507 in number) between two platforms were used for analysis. Background subtracted raw data were quantile normalized. Probes for which intensity were greater than. sample median level in at least half the arrays for one experimental condition in. a dataset were considered present; absent probes were removed. Further differentially expressed probbes between OL and OPC were identified by using R Bioconductor package 'limma'. P-values were adjusted to correct for multiple testing using FDR (Benjamini-Hochberg). Probes for which the difference between groups were > or = 2 fold and the adjusted P-value<0.05 were considered differentially expressed.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE245032 | GEO | 2024/02/14

REPOSITORIES: GEO

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Project description:ADHD is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the Spontaneously Hypertensive Rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11 and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1 and Hes6.The epigenetic genes Crebbp, Mecp2 and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR.

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Probe level meta analysis of microarray data to understand the role of retrotransposable elements in myelination.

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