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NAVIGATING THE TRANSLATIONAL RESEARCHER THROUGH A COMPLEX OF ANIMAL AND BIOLOGICAL RESOURCES Rat Models and Resources Howard J. Jacob, Ph.D. Medical College of Wisconsin http://hmgc.mcw.edu http://pga.mcw.edu http://rgd.mcw.edu Overview Different Types of Rat data sets Rat Genome Database Disease Portals Comparative Genomics Building interactive physiological genomic databases Genomic/Genetic Datasets for the Rat Genomic sequence 6.8X + 1.5X in July, ~600,000 ESTs, 6500 flcDNA 10,000 genetic markers 4 Bacterial Artificial Chromosome libraries, 2 Yeast Artificial Chromosome libraries SNP discovery and maps under construction. ~1.5M SNPs. SNP chips being developed Microarray chips 100,000+ siRNA probes 726 strains (plus 300+ genetically modified) KOs possible via ENU and gene screening Cloning possible 1029 Quantitative Trait Loci or biological phenotypes assigned to the rat genome Disease, Phenotype and Gene Ontologies Direct translation to human and mouse via comparative genomics 1,203,236 publications in Pubmed Rat Genome Database Developed to support the NIH Rat Genome Project Provides genomics/genetic and phenotyping data http://rgd.mcw.edu depression Rat Genome Database Provides genomics data and is being developed into a phenome database Problem: Most Investigators interested in translational research will not know how to find these data Solution: Development of Disease Portals Comparative Genomics Brings together investigators interested in the same disease but who study different models or clinical samples Human Chr 1 Rat Chr 13 cM D13rat107 1 2 3 4 5 Microalbuminuria 8.0 Proteinuria 6.1 MAP 8.4 SAP 6.9 DAP 8.2 54 32 1 2.3 D13mgh13 8 D13rat88 2.2 2.2 D13rat91 D13rat101 3.6 D13rat127 3.6 D13rat177 2.5 D13arb10 D13rat77 D13got43 12 French Canadian African American 1. Anthropometrics including BMI, % bodyfat, skinfold thicknesses, thigh and arm circumferences: LODs 1. 2.9, 3. 3.4, 4. 2.4, 5. 3.1, 6. 2.6, 7. 3.9, 8. 3.6, 9. 2.7, 10. 2.6, 11. 2.8, 12. 2.4, 13. 3.7, 14. 2.3. 2. Supine DBP LOD 2.1 15. Fasting insulin LOD 2.6 16. Awake mean BP LOD 1.4 17. Awake DBP LOD 1.4 18. Postmath DBP LOD 1.3 19. Fasting leptin LOD 1.6 1. Standing DBP LOD 1.9 2. Sitting stroke volume LOD 1.7 D13rat30 12 D13rat130 1.4 1.4 D13mit5 D13rat197 D13rat183 15 14 12 2 10 13 19 3.6 3.6 6.5 2 3 1 9 11 8 7 6 4 1 5 18 D13rat57 D13Mit4 D13rat192 17 16 2 Systems Biology & Physiological Genomics New types of data New ways to integrate the data Hopefully new ways to ask questions Gene Knock-out Phenotype Interactive discovery tool All physiological data present All phenotyping protocols available Ability to ask questions and run statistical analyses on the data set http://pga.mcw.edu PhysGen Home Page OVERVIEW DATA Aims Participants Protocols Deliverables Strains Organization Citing Data Strain Profile COMPONENTS About PGA Genomics News Phenotyping Order Research Services Education Bioinformatics Presentations Education Collaborators Visiting Scientist LINKS Publications Microarray Genotyping Workshops Other PGAs Atmosphere Diet RGD Conditioning Download Phenotyping Analysis Genome Scanner Where in the genome of the SS rat does hypertension map? 429,603 measurements Protective Genes Use of Microarrays to identify Differentially Expressed Genes in Consomic Rats Differential gene expression in response to high salt diet Dahl S • Low salt • 16 hours Consomic SS.BN13 • 3 days • 14 days Liang et al. Physio Gen., 2002. UniGene microarray Summary Rat Genetics and Genomics enable translation between different species. Extensive resources that require integration Rat Bioinformatics continues to improve Rat biology is a driver Need to enable hypothesis testing from online data Need to continue to capture data without extensive data curation—a major issue