E-GEOD-7614
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA100153
PROVIDER: E-GEOD-7614 | ExpressionAtlas | 2014-07-03
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster
| PRJNA100153 | ENA
Project description:Transcriptional Response to Alcohol Exposure in Drosophila melanogaster
| PRJNA96289 | ENA
Project description:The National Institute on Alcohol Abuse and Alcoholism has estimated that approximately 14 million people in the United States suffer from alcoholism. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Whereas environmental factors, such as stress and social experience, contribute to individual variation in sensitivity to chronic alcohol consumption, genetic factors have also been implicated. However, genetic polymorphisms that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of olfactory sensitivity and, concomitant with development of tolerance, altered transcription of enzymes associated with fatty acid biosynthesis. Our results identify key enzymes in conserved metabolic pathways that may contribute to human alcohol sensitivity. Experiment Overall Design: Alcohol sensitivity in Drosophila melanogaster can be quantified in an inebriometer. The elution time from the column is used as a measure of sensitivity to alcohol intoxication. Overall design: We collected 3-5 day old Canton S flies either without exposure to ethanol (control group), immediately after passage through the inebriometer, or from a population that had developed tolerance 2h after the initial ethanol exposure.
2008-03-13 | E-GEOD-5382 | biostudies-arrayexpress
Project description:The National Institute on Alcohol Abuse and Alcoholism has estimated that approximately 14 million people in the United States suffer from alcoholism. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Whereas environmental factors, such as stress and social experience, contribute to individual variation in sensitivity to chronic alcohol consumption, genetic factors have also been implicated. However, genetic polymorphisms that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance. We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of olfactory sensitivity and, concomitant with development of tolerance, altered transcription of enzymes associated with fatty acid biosynthesis. Our results identify key enzymes in conserved metabolic pathways that may contribute to human alcohol sensitivity. Keywords: Drosophila, model system, alcohol sensitivity, tolerance
2006-07-27 | GSE5382 | GEO
Project description:Sustained or repeated exposure to sedating drugs such as alcohol triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Drug-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most that may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct drugs. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. A total of six samples. Two H4Ac ChIP-chip biological replicates from heads of Drosophila (untreated, IP/input), two H4Ac ChIP-chip biological replicates from heads of Drosophila sedated with benzyl alcohol (IP_treated/IP_control), and two H4Ac ChIP-chip biological replicates from heads of Drosophila sedated with ethanol (IP_treated/IP_control) are included.
2013-09-05 | E-GEOD-48449 | biostudies-arrayexpress
Project description:Fetal alcohol exposure can lead to developmental abnormalities, intellectual disability, and behavioral changes, collectively termed fetal alcohol spectrum disorder (FASD). In 2015, the CDC found that 1 in 10 pregnant women report alcohol use and more than 3 million women in the USA are at risk of exposing their developing baby to alcohol. Identifying genetic risk alleles for FASD is challenging, since time, dose and frequency of exposure are often unknown, and phenotypic manifestations of FASD are diverse and become evident long after exposure. Drosophila melanogaster presents an excellent model to study developmental effects of alcohol exposure, because virtually unlimited numbers of individuals of the same genotype can be reared rapidly and economically under well-controlled environmental conditions without regulatory restrictions. Furthermore, flies exposed to alcohol undergo physiological and behavioral changes that resemble human alcohol-related phenotypes. Flies reared on ethanol-supplemented medium show decreased viability, reduced sensitivity to ethanol, and disrupted sleep and activity patterns. To assess alcohol-modulated gene expression in the brains of flies reared on alcohol, we performed single cell RNA sequencing and resolved cell clusters with differentially expressed genes representing distinct neuronal and glial populations. We observed extensive sexual dimorphism. Two clusters associated with glial biomarkers showed greater differential gene expression in males, whereas mushroom body-derived cells exhibited a greater degree of differential gene expression in females. Results obtained from these studies provide a blueprint for translational studies on alcohol-induced effects on gene expression in the brain that may contribute to or result from FASD in human populations.
2021-08-11 | GSE172231 | GEO
Project description:Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. We performed artificial selection for alcohol sensitivity for 25 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans. Keywords: artificial selection, whole genome expression profiling
2007-11-20 | GSE7614 | GEO
Project description:Sustained or repeated exposure to sedating drugs such as alcohol triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Drug-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most that may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct drugs. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol.
2013-09-05 | GSE48449 | GEO
Project description:Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. We performed artificial selection for alcohol sensitivity for 25 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q < 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P-element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans. Experiment Overall Design: Starting with flies from Raleigh natural population (see material and methods) we performed artificial selection for alcohol sensitivity for 35 generation. In each generations we scored 60 males and females, separately, from each line (resistant, sensitive, and control)using inebriometer, and the 20 highest-scoring flies from the resistant lines and the 20 lowest-scoring flies from the sensitive lines were selected as parents for the next generation. Control line flies were scored each generation and 20 random flies were used as parents. Experiment Overall Design: At generation 25, two replicates of 15 three-five day old virgin males and females were collected from each selection line. Total RNA was extracted from the 24 samples . Biotinylated cRNA probes were hybridized to high density oligonucleotide microarrays (Affymetrix, Inc. Drosophila GeneChip 2.0) and visualized with a streptavidin-phycoerythrin conjugate, as described in the Affymetrix GeneChip Expression Analysis Technical Manual (2000), using internal references for quantification. The quantitative estimate of expression of each probe set is the Signal (Sig) metric, as described in the Affymetrix Microarray Suite, Version 5.0.
2008-03-13 | E-GEOD-7614 | biostudies-arrayexpress