Splicing landscape of the eight collaborative cross founder strains

Christina Zheng, Beth Wilmot, Nicole A R Walter, Denesa Oberbeck, Sunita Kawane, Robert Searles, Shannon McWeeney, Robert Hitzemann

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Article number52
JournalBMC Genomics
Volume16
Issue number1
DOIs
StatePublished - Feb 5 2015

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Transcriptome
Exons
Population
High-Throughput Nucleotide Sequencing
Inbred Strains Mice
Alternative Splicing
Genome
Guidelines
Brain
Surveys and Questionnaires

Keywords

  • Collaborative Cross
  • Splicing landscape
  • Strain specific splicing

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Splicing landscape of the eight collaborative cross founder strains. / Zheng, Christina; Wilmot, Beth; Walter, Nicole A R; Oberbeck, Denesa; Kawane, Sunita; Searles, Robert; McWeeney, Shannon; Hitzemann, Robert.

In: BMC Genomics, Vol. 16, No. 1, 52, 05.02.2015.

Research output: Contribution to journalArticle

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