A list of genes whose transcript abundance in the PFC changed significantly 4 hours after an acute dose of ethanol (1.8 g/kg). This list was generated using Fisher's Combined Probability test to analyze saline vs ethanol S-scores across B6 and D2 inbred strains (n=3) and 27 BXD RI lines (n=1). Statistical significance was determined using 1,000 permutations of S-score data and selecting for probe-sets with q-values < 0.05. Aaron Wolen 5-26-10.
Authors:
Wolen AR, Phillips CA, Langston MA, Putman AH, Vorster PJ, Bruce NA, York TP, Williams RW, Miles MF
Activation of the mesolimbic dopamine reward pathway by acute ethanol produces reinforcement and changes in gene expression that appear to be crucial to the molecular basis for adaptive behaviors and addiction. The inbred mouse strains DBA/2J and C57BL/6J exhibit contrasting acute behavioral responses to ethanol. We used oligonucleotide microarrays and bioinformatics methods to characterize patterns of gene expression in three brain regions of the mesolimbic reward pathway of these strains. Expression profiling included examination of both differences in gene expression 4 h after saline injection or acute ethanol (2 g/kg). Using a rigorous stepwise method for microarray analysis, we identified 788 genes differentially expressed in control DBA/2J versus C57BL/6J mice and 307 ethanol-regulated genes in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. There were strikingly divergent patterns of ethanol-responsive gene expression in the two strains. Ethanol-responsive genes also showed clustering at discrete chromosomal regions, suggesting local chromatin effects in regulation. Ethanol-regulated genes were generally related to neuroplasticity, but regulation of discrete functional groups and pathways was brain region specific: glucocorticoid signaling, neurogenesis, and myelination in the prefrontal cortex; neuropeptide signaling and developmental genes, including factor Bdnf, in the nucleus accumbens; and retinoic acid signaling in the ventral tegmental area. Bioinformatics analysis identified several potential candidate genes for quantitative trait loci linked to ethanol behaviors, further supporting a role for expression profiling in identifying genes for complex traits. Brain region-specific changes in signaling and neuronal plasticity may be critical components in development of lasting ethanol behavioral phenotypes such as dependence, sensitization, and craving.
A list of the 307 genes found to be upregulated or downregulated by ethanol in PFC, VTA or NA of B6 or D2 mice. ID number represents cluster membership from Figure 4.
Authors:
Kerns RT, Ravindranathan A, Hassan S, Cage MP, York T, Sikela JM, Williams RW, Miles MF
Hippocampus Gene Expression Correlates for NX_ADIST_3 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The NX_ADIST_3 measures Naloxone induced Morphine Withdrawal TOTAL vertical activity counts in 15 minutes under the domain Morphine. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
QTL for nicotine sensitivity on Chr13 at D13Mit59 (37.58 Mbp , Build 37)
Description:
nicotine sensitivity spans 12.58 - 62.58 Mbp (NCBI Build 37) on Chr13. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for ethanol withdrawal on Chr13 at D13Ncvs35 (71.29 Mbp , Build 37)
Description:
ethanol withdrawal spans 46.29 - 96.29 Mbp (NCBI Build 37) on Chr13. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Genes associated with Homo sapiens that interact with the MeSH term 'arsenite' (C015001). Incorporates data from 3 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Hydrogen Peroxide' (D006861). Incorporates data from 4 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Valproic Acid' (D014635). Incorporates data from 1238 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'Diazinon' (D003976). Incorporates data from 2 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Genes associated with Homo sapiens that interact with the MeSH term 'pirinixic acid' (C006253). Incorporates data from 1 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Table 1. Proteins found to be modified by at least two drugs of abuse; Alcohol, Amphetamine/methamphetamine, cocaine Marijuana, Morphine/heroin/butorphanol, Nicotine.
QTL associated with spontaneous crescentic glomerulonephritis QTL 5. The confidence interval is Chr13:35968794-96872609 bp,+strand
Authors:
Hamano Y, Tsukamoto K, Abe M, Sun GD, Zhang D, Fujii H, Matsuoka S, Tanaka M, Ishida-Okawara A, Tachikawa H, Nishimura H, Tokunaka K, Hirose S, Suzuki K
Analysis performed on raw data in GEO2R with default settings. These are derived sets from the publication data. The data is available in GEO, and was analyzed using default setting in their suite of tools. This allowed the production of age independent differential expression set to be created for bHR vs bLR by brain region. Something not presented in the paper.
Analysis performed on raw data in GEO2R with default settings. These are derived sets from the publication data. The data is available in GEO, and was analyzed using default setting in their suite of tools. This allowed the production of age independent differential expression set to be created for bHR vs bLR by brain region. Something not presented in the paper.
QTL associated with Angiostrongylus costaricensis nematode susceptibility 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (53042863)
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