title: Splicing landscape of the eight collaborative cross founder strains.
abstract: BACKGROUND
  The Collaborative Cross (CC) is a large panel of genetically diverse recombinant inbred mouse strains specifically designed to provide a systems genetics resource for the study of complex traits. In part, the utility of the CC stems from the extensive genome-wide annotations of founder strain sequence and structural variation. Still missing, however, are transcriptome-specific annotations of the CC founder strains that could further enhance the utility of this resource.
  
  
  RESULTS
  We provide a comprehensive survey of the splicing landscape of the 8 CC founder strains by leveraging the high level of alternative splicing within the brain. Using deep transcriptome sequencing, we found that a majority of the splicing landscape is conserved among the 8 strains, with ~65% of junctions being shared by at least 2 strains. We, however, found a large number of potential strain-specific splicing events as well, with an average of ~3000 and ~500 with ≥3 and ≥10 sequence read coverage, respectively, within each strain. To better understand strain-specific splicing within the CC founder strains, we defined criteria for and identified high-confidence strain-specific splicing events. These splicing events were defined as exon-exon junctions 1) found within only one strain, 2) with a read coverage ≥10, and 3) defined by a canonical splice site. With these criteria, a total of 1509 high-confidence strain-specific splicing events were identified, with the majority found within two of the wild-derived strains, CAST and PWK. Strikingly, the overwhelming majority, 94%, of these strain-specific splicing events are not yet annotated. Strain-specific splicing was also located within genomic regions recently reported to be over- and under-represented within CC populations.
  
  
  CONCLUSIONS
  Phenotypic characterization of CC populations is increasing; thus these results will not only aid in further elucidating the transcriptomic architecture of the individual CC founder strains, but they will also help in guiding the utilization of the CC populations in the study of complex traits. This report is also the first to establish guidelines in defining and identifying strain-specific splicing across different mouse strains.
authors: Department of Medical Informatics and Clinical Epidemiology, Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, Oregon, USA. zheng@ohsu.edu.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA. zheng@ohsu.edu.
authors: Christina L
authors: CL
authors: Zheng
authors: Department of Medical Informatics and Clinical Epidemiology, Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, Oregon, USA. wilmotb@ohsu.edu.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA. wilmotb@ohsu.edu.|Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon, USA. wilmotb@ohsu.edu.
authors: Beth
authors: B
authors: Wilmot
authors: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. waltern@ohsu.edu.|Portland Alcohol Research Center, Oregon Health & Science University, Portland, Oregon, USA. waltern@ohsu.edu.
authors: Nicole Ar
authors: NA
authors: Walter
authors: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. oberbeck@ohsu.edu.
authors: Denesa
authors: D
authors: Oberbeck
authors: Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon, USA. kawanes@ohsu.edu.
authors: Sunita
authors: S
authors: Kawane
authors: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, USA. searlesr@ohsu.edu.
authors: Robert P
authors: RP
authors: Searles
authors: Department of Medical Informatics and Clinical Epidemiology, Division of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, Oregon, USA. mcweeney@ohsu.edu.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA. mcweeney@ohsu.edu.|Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon, USA. mcweeney@ohsu.edu.|Department of Public Health and Preventative Medicine, Division of Biostatistics, Oregon Health & Science University, Portland, Oregon, USA. mcweeney@ohsu.edu.
authors: Shannon K
authors: SK
authors: McWeeney
authors: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. hitzeman@ohsu.edu.|Veterans Affairs Research Service, Portland, OR, USA. hitzeman@ohsu.edu.
authors: Robert
authors: R
authors: Hitzemann
mesh_terms: D000818:Animals; D016678:Genome; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D058977:Molecular Sequence Annotation; D040641:Quantitative Trait Loci / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D059467:Transcriptome
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