Allele-specific expression in familial pancreatic cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Aik Choon Tan
PROVIDER: E-GEOD-9596 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Pharmaceuticals are pseudo persistent aquatic pollutants with unknown effects at environmentally relevant concentrations. Atlantic salmon (Salmo salar) were exposed to Acetaminophen: 54.77 ± 34.67; Atenolol: 11.08 ± 7.98 and Carbamazepine: 7.85 ± 0.13 µg•L-1 for 5 days. After Acetaminophen treatment, 19 proteins were differently expressed, of which 11 were significant with respect to the control group (eight up-regulated and three down-regulated). After Atenolol treatment, 7 differently expressed proteins were obtained in comparison with the control, of which 6 could be identified (four up-regulated and 2 down-regulated). Carbamazepine exposure resulted in 15 differently expressed proteins compared with the control, with 10 of them identified (seven up-regulated and three down-regulated). Out of these, 3 features were common between Acetaminophen and Carbamazepine and one between Carbamazepine and Atenolol. One feature was common across all treatments. Principal component analysis and heat map clustering showed a clear grouping of the variability due to the applied treatments. The obtained data suggest (1) that exposure to environmentally relevant concentrations of the pharmaceuticals alters the hepatic protein expression profile of the Atlantic salmon; and (2) the existence of treatment specific processes that may be useful for biomarker development.
2014-11-18 | PXD001354 | Pride
Project description:Microarray experiments have generally focused on magnitude of gene expression changes in pathological conditions, thereby using the method as a high throughput screen to identify candidate marker genes and/or to validate phenotypic differences. We have used novel strategies to extract additional information from array studies, including expression variability and coordination, from which organizational principles of transcriptomes are emerging. We have reported that expression level, variability and coordination of numerous genes are regulated in brains of Gja1-/- mice with respect to wildtypes. Moreover, expression coordination with Gja1 in wildtypes largely predicted expression regulation in Gja1-/- tissues. We now report a remarkable overlap between regulations in Gja1-/- and Gjb1-/- brains, and that both differ markedly from those in Gja9-/- brain. Since in brain these three connexins are expressed in different cell types (Gja1 in astrocytes, and ependymal and vascular cells, Gjb1 in oligodendrocytes, and Gja9 in neurons and microglia), and because astrocytes and oligodendrocytes may form syncytia coupled by gap junction channels, these observations suggest the existence of distinct connexin-dependent panglial and neuronal transcriptomic networks. Such networks, where linkage partners are rearranged and strengths modified in brains of knockouts, may explain downstream and parallel 'ripples' of phenotypic change resulting from single gene alterations as the composition and interactions of transcription factor networks in the wildtype brain were identified and found to be altered disruption of Gja1 or Gjb1. The transcription factors also formed network hubs with genes from other functional categories, thus allowing regulation of one functional pathway through manipulation of another. Keywords: genetic modification The brain transcriptomes of Gja9(-/-) and Gja9(+/-) P10 mice were compared to that of P10 wildtype mouse using the "multiple yellow" design in which extracts of biological replicas of the same genotype were hybridized with six 27k AECOM mouse cDNA microarrays (4 biological replicas of each genotype). These data were further compared to previously reported data on brain of neonatal wildtype, Gja1(-/-), Gja1(+/-) and Gjb1(-/-) mice (four biological replicas per genotype, reference sample design).
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