Using baseline transcriptional connectomes in rat to identify genetic pathways associated with predisposition to complex traits

Abstract

Although rat is a critical model organism in preclinical medications development, its use in systems genetics studies remains sparse. The PhenoGen database and website contain detailed information on the qualitative and quantitative aspects of the rat brain, liver, heart, and brown adipose transcriptome. This database has been generated using the HXB/BXH recombinant inbred panel and is being expanded to a hybrid rat diversity panel that includes many common inbred strains as well. By using such a panel, the PhenoGen project has created a renewable and cumulative resource for the rat genomics community. The database has been used to reconstruct the brain transcriptome identifying both annotated and unannotated transcribed elements that range in size from 20 nucleotides to over 30,000 nucleotides and elements that have a wide variety of roles in the cell including generation of proteins and regulation of the transcription and translation processes. In all 4 tissues, baseline transcriptional connectomes have been generated to model the relationships among transcripts. These connectomes can be used to identify genetic pathways associated with complex traits and to gain insight into biological function of individual transcripts. The PhenoGen website contains tools that allow the user to explore qualitative features of individual genes and to see how the gene relates to other genes within a tissue. The PhenoGen database and website continue to grow and to make use of the latest statistical methods for systems genetics creating a national resource for the rat genomics community.