Splicing landscape of the eight collaborative cross founder strains

Area of Science:

• Genomics and Transcriptomics
• Systems Genetics
• Mouse Models

Background:

• The Collaborative Cross (CC) is a vital resource for studying complex traits, built on genetically diverse mouse strains.
• Existing genome-wide annotations of CC founder strains are extensive, but transcriptome-specific data is lacking.
• Enhanced transcriptomic annotations are needed to fully leverage the CC resource for complex trait research.

Purpose of the Study:

• To comprehensively survey the splicing landscape across the eight CC founder strains.
• To identify and characterize strain-specific splicing events within the CC founder strains.
• To establish guidelines for defining and identifying strain-specific splicing events in mouse populations.

Main Methods:

• Deep transcriptome sequencing was employed to analyze the splicing landscape.
• Focus was placed on alternative splicing within the brain tissue of the CC founder strains.
• Criteria were defined to identify high-confidence strain-specific splicing events (single-strain junctions, read coverage ≥10, canonical splice sites).

Main Results:

• A majority of the splicing landscape (~65% of junctions) is conserved among the eight CC founder strains.
• A significant number of potential strain-specific splicing events were identified, with an average of ~3000 per strain.
• 1509 high-confidence strain-specific splicing events were identified, predominantly in CAST and PWK strains, with 94% unannotated.

Conclusions:

• The identified strain-specific splicing events provide crucial transcriptomic annotations for CC founder strains.
• These findings will aid in understanding the transcriptomic architecture and guiding the use of CC populations for complex trait studies.
• This study establishes the first guidelines for defining and identifying strain-specific splicing across different mouse strains.