Using the Phenogen website for 'in silico' analysis of morphine-induced analgesia: identifying candidate genes.
The identification of genes that contribute to polygenic (complex) behavioral phenotypes is a key goal of current genetic research. One approach to this goal is to combine gene expression information with genetic information, i.e. to map chromosomal regions that regulate gene expression levels. This approach has been termed 'genetical genomics', and, when used in conjunction with the identification of genomic regions (QTLs) that regulate the complex physiological trait under investigation, provides a strong basis for candidate gene discovery. In this paper, we describe the implementation of the genetical genomic/phenotypic approach to identify candidate genes for sensitivity to the analgesic effect of morphine in BXD recombinant inbred mice. Our analysis was performed 'in silico', using an online interactive resource called PhenoGen (http://phenogen.ucdenver.edu). We describe in detail the use of this resource, which identified a set of candidate genes, some of whose products regulate the cellular localization and activity of the mu opiate receptor. The results demonstrate how PhenoGen can be used to identify a novel set of genes that can be further investigated for their potential role in pain, morphine analgesia and/or morphine tolerance.
University of Colorado Denver, School of Medicine, Department of Pharmacology, Aurora, CO 80045, USA.
Paula L
PL
Hoffman
Beth
B
Bennett
Laura M
LM
Saba
Sanjiv V
SV
Bhave
Phyllis J
PJ
Carosone-Link
Cheryl K
CK
Hornbaker
Katerina J
KJ
Kechris
Robert W
RW
Williams
Boris
B
Tabakoff
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D001931:Brain Mapping; D030541:Databases, Genetic; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D056726:Genetic Association Studies / Q000379:methods*; D016678:Genome; D020407:Internet; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D017288:Pain Threshold / Q000187:drug effects*; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D012985:Software Design; D013697:Thermosensing / Q000187:drug effects / Q000235:genetics
D000701:Analgesics, Opioid; D009020:Morphine