title: Influence of sex on genetic regulation of "drinking in the dark" alcohol consumption.
abstract: The ILSXISS (LXS) recombinant inbred (RI) panel of mice is a valuable resource for genetic mapping studies of complex traits, due to its genetic diversity and large number of strains. Male and female mice from this panel were used to investigate genetic influences on alcohol consumption in the "drinking in the dark" (DID) model. Male mice (38 strains) and female mice (36 strains) were given access to 20% ethanol during the early phase of their circadian dark cycle for four consecutive days. The first principal component of alcohol consumption measures on days 2, 3, and 4 was used as a phenotype (DID phenotype) to calculate QTLs, using a SNP marker set for the LXS RI panel. Five QTLs were identified, three of which included a significant genotype by sex interaction, i.e., a significant genotype effect in males and not females. To investigate candidate genes associated with the DID phenotype, data from brain microarray analysis (Affymetrix Mouse Exon 1.0 ST Arrays) of male LXS RI strains were combined with RNA-Seq data (mouse brain transcriptome reconstruction) from the parental ILS and ISS strains in order to identify expressed mouse brain transcripts. Candidate genes were determined based on common eQTL and DID phenotype QTL regions and correlation of transcript expression levels with the DID phenotype. The resulting candidate genes (in particular, Arntl/Bmal1) focused attention on the influence of circadian regulation on the variation in the DID phenotype in this population of mice.
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E. Montview Blvd., Campus Box: C238, Aurora, CO, 80045, USA, lauren.vanderlinden@ucdenver.edu.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Vanderlinden
authors.forename: Laura M
authors.initials: LM
authors.lastname: Saba
authors.forename: Beth
authors.initials: B
authors.lastname: Bennett
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hoffman
authors.forename: Boris
authors.initials: B
authors.lastname: Tabakoff
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D025341:Principal Component Analysis; D040641:Quantitative Trait Loci / Q000235:genetics*; D012737:Sex Factors
chemical_list: C497397:Arnt protein, mouse; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator