The overall goal of this program is to extend the use of rat models for clinical translation through establishing an animal resource and genomic dataset to facilitate the translation of laboratory research to clinical relevance. Specifically, this project will develop the Hybrid Rat Diversity Panel (HRDP) as the source of the animal models and baseline molecular and physiological phenotypes underlying the National Rat Genetics Resource Program. To achieve this goal, we propose the following four specific aims: 1) to establish the 96 strain Hybrid Rat Diversity Panel comprised of 33 classic inbred strains, 30 HXB/BXH recombinant inbred strains and 33 FEXL/LXFE recombinant inbred strains, 2) to phenotypically characterize, maintain and distribute the HRDP, 3) to complete genomic sequencing on the full HRDP and 4) and provide data analysis, integration and dissemination primarily through the Rat Genome Database (RGD). This resource will be used to study mechanisms of complex disease traits through systems genetics by providing access to a renewable panel of inbred rat strains and biobanked tissues, reusable phenotypic data, reusable genomic sequence and strain specific variants, and the infrastructure to explore, analyze and visualize these resources through the HRDP Portal at RGD. The HRDP will have broad utility to the scientific community through the genetic and phenotypic diversity represented in the 96 strain panel used to study hypertension, stroke, diabetes, cancer, arthritis, reproductive disorders, asthma, aging, alcohol preference, anxiety, and exercise.
This R24 resource grant builds upon our existing infrastructure to develop the 96 strain Hybrid Rat Diversity Panel (HRDP) to be used to broadly study disease mechanisms, the impact of the environment, and for therapeutic drug development. This panel of rats will be used to map complex traits through powerful analyses of genomic, transcriptomic and phenotypic data. In addition, the HRDP provides a genetically stable population that can be reused and renewed.