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Hybrid Rat Diversity Program (HRDP): A Rat Resource for Systems Genetics

Genetic susceptibility to disease, sensitivity to environmental elements, and pharmacogenomics are critical components of the concepts of precision medicine. Rats are a major model for studying complex disease mechanisms, behavioral phenotypes, environmental factors, and for drug development and discovery. Inbred rat strains control for genetic background and allow for repeated, reproducible molecular, cellular, and whole animal phenotyping. Through the development of the Hybrid Rat Diversity Program, a powerful panel of inbred rats with genomic, physiologic, and behavioral phenotype data will serve as a catalyst for research in many fields. The Hybrid Rat Diversity Panel (HRDP) will consist of 96 inbred rat strains to maximize power to detect specific genetic loci associated with complex traits while maximizing the genetic diversity among strains. The 96 strain panel consists of 33 genetically diverse inbred strains and two panels of recombinant inbred panels: FXLE/LEXF (33 strains, Japan) and HXB/BXH (30 strains, Czech Republic). Embryo resuscitation and breeding are underway at the Medical College of Wisconsin (MCW). Whole genome sequencing for all 96 strains will be performed by the Genomic Sciences and Precision Medicine Center (MCW) sequencing core to achieve 30X coverage (Illumina NovaSeq S4). Liver and brain transcriptome analysis will be done for the entire HRDP panel through PhenoGen (http://phenogen.ucdenver.edu) at the University of Colorado (Tabakoff and Saba). Genomic, phenotype, and strain information will be made available through the Hybrid Rat Diversity Panel portal at the Rat Genome Database (http://rgd.mcw.edu). MCW will partner with the Rat Resource & Research Center (RRRC, http://www.rrrc.us) at the University of Missouri for strain distribution. The HRDP will provide a genetically stable population of rat strains with fully sequenced genomes, transcriptomes for brain and liver, and general phenotypic characterization to be used for systems genetic studies and fine mapping of complex traits.