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Series GSE7614 Query DataSets for GSE7614
Status Public on Nov 20, 2007
Title Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster
Organism Drosophila melanogaster
Experiment type Expression profiling by array
Summary 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
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.
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.
Contributor(s) Morozova TV, Anholt RR, Mackay TF
Citation(s) 17973985
Submission date Apr 25, 2007
Last update date Aug 28, 2018
Contact name Tatiana V Morozova
Organization name NCSU
Department zoology
Lab Anholt
Street address campus box 7617
City Raleigh
State/province NC
ZIP/Postal code 27695
Country USA
Platforms (1)
GPL1322 [Drosophila_2] Affymetrix Drosophila Genome 2.0 Array
Samples (24)
GSM183815 control1m1
GSM183816 control1m2
GSM183817 control1f1
BioProject PRJNA100153

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE7614_RAW.tar 52.1 Mb (http)(custom) TAR (of CEL, CHP)
Raw data provided as supplementary file
Processed data provided as supplementary file

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