title: Genome characterization of the selected long- and short-sleep mouse lines.
abstract: The Inbred Long- and Short-Sleep (ILS, ISS) mouse lines were selected for differences in acute ethanol sensitivity using the loss of righting response (LORR) as the selection trait. The lines show an over tenfold difference in LORR and, along with a recombinant inbred panel derived from them (the LXS), have been widely used to dissect the genetic underpinnings of acute ethanol sensitivity. Here we have sequenced the genomes of the ILS and ISS to investigate the DNA variants that contribute to their sensitivity difference. We identified ~2.7 million high-confidence SNPs and small indels and ~7000 structural variants between the lines; variants were found to occur in 6382 annotated genes. Using a hidden Markov model, we were able to reconstruct the genome-wide ancestry patterns of the eight inbred progenitor strains from which the ILS and ISS were derived, and found that quantitative trait loci that have been mapped for LORR were slightly enriched for DNA variants. Finally, by mapping and quantifying RNA-seq reads from the ILS and ISS to their strain-specific genomes rather than to the reference genome, we found a substantial improvement in a differential expression analysis between the lines. This work will help in identifying and characterizing the DNA sequence variants that contribute to the difference in ethanol sensitivity between the ILS and ISS and will also aid in accurate quantification of RNA-seq data generated from the LXS RIs.
authors.affiliation: BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80309, USA. Robin.Dowell@colorado.edu.|Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, 80309, USA. Robin.Dowell@colorado.edu.|Department of Computer Science, University of Colorado Boulder, Boulder, CO, 80309, USA. Robin.Dowell@colorado.edu.
authors.forename: Robin
authors.initials: R
authors.lastname: Dowell
authors.affiliation: BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80309, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Odell
authors.affiliation: BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80309, USA.|Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, 80309, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Richmond
authors.affiliation: Department of Computer Science, University of Colorado Boulder, Boulder, CO, 80309, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Malmer
authors.affiliation: Center for Genes, Environment and Health, National Jewish Health, Denver, CO, 80206, USA.
authors.forename: Eitan
authors.initials: E
authors.lastname: Halper-Stromberg
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Bennett
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Larson
authors.affiliation: Center for Genes, Environment and Health, National Jewish Health, Denver, CO, 80206, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Leach
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 80045, USA. Richard.Radcliffe@ucdenver.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Radcliffe
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D000431:Ethanol / Q000494:pharmacology; D016678:Genome / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012890:Sleep / Q000187:drug effects / Q000235:genetics* / Q000502:physiology
chemical_list: D000431:Ethanol