Genome-to-phenome research in rats: progress and perspectives

Area of Science:

• Genomics
• Systems Biology
• Animal Models

Background:

• Rats are crucial model organisms for human health and disease research owing to their shorter lifespan compared to humans.
• Significant advancements in rat genome sequencing and assembly over the past 20 years, including whole genome sequencing (WGS) of 47 strains, have been achieved.
• Parallel advancements in rat phenome programs and databases have facilitated the collection of extensive genome and phenome information.

Purpose of the Study:

• To explore the connection between rat genome variants and complex phenotypes.
• To investigate the role of alternative transcriptional start (ATS) and polyadenylation (APA) sites in mediating genome-to-phenome information transfer.
• To demonstrate how alternative transcriptome analysis can identify phenome-related causal pathways in rats.

Main Methods:

• Whole genome sequencing (WGS) of multiple rat strains.
• Analysis of genome variants for association with quantitative trait loci (QTLs).
• Alternative transcriptome analysis focusing on alternative transcriptional start (ATS) and polyadenylation (APA) sites.

Main Results:

• Discovery of numerous genome variants in rats, enabling association analyses for complex phenotypes.
• Identification of strain, chromosome, and gene functional evolutions through DNA variant analysis.
• Demonstration that alternative transcriptome analysis enriches for phenome-related causal pathways in rats.

Conclusions:

• Integrative genomics and systems genetics approaches are vital for bridging the gap between genome and phenome data in rats.
• Differential usage of ATS and APA sites plays a key role in transferring genomic information to the phenome.
• Advanced genome-to-phenome assays will further enhance the utility of rats in human biomedical research.