Comparison of sequence variants in transcriptomic control regions across 17 mouse genomes

Area of Science:

• Genomics
• Bioinformatics
• Systems Genetics

Background:

• The laboratory mouse is a crucial mammalian model organism in biomedical research.
• Comprehensive annotation of functional variation in the mouse genome is essential for advancing research.
• The mouse ENCODE project identified approximately 300,000 functional elements regulating gene expression across 19 tissue types.

Purpose of the Study:

• To compare sequence variation in functional genomic elements across 17 inbred mouse strains.
• To create a database of aligned sequences for regulatory elements.
• To develop a tool for visualizing and comparing sequence variation.

Main Methods:

• Sequencing of approximately 300,000 functional elements (promoters, enhancers, CTCF binding sites) across 17 mouse strains.
• Alignment of sequences for each cis-regulatory element to the genomes of the 17 strains.
• Development of an online tool for visualization and comparison of sequence variation.

Main Results:

• A database of approximately 5 million aligned sequences was generated, enabling interrogation of functional element variation.
• The study identified sequence variation in cis-regulatory elements across 19 tissues/cell types in commonly used mouse strains.
• The Collaborative Cross founder strains were found to capture the most variability in ENCODE elements among the 17 sequenced strains.

Conclusions:

• The generated database and online tool provide a valuable resource for studying functional variation in the mouse genome.
• The findings emphasize the utility of the Collaborative Cross resource for accelerating gene discovery in complex traits.
• This work facilitates a deeper understanding of genotype-phenotype relationships in mouse models.