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Howard J. Jacob, Ph.D. Medical College of Wisconsin hmgc.mcw pga.mcw

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

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Howard J. Jacob, Ph.D. Medical College of Wisconsin hmgc.mcw pga.mcw

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  1. NAVIGATING THE TRANSLATIONAL RESEARCHER THROUGH A COMPLEX OFANIMAL 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

  2. Overview • Different Types of Rat data sets • Rat Genome Database • Disease Portals • Comparative Genomics • Building interactive physiological genomic databases

  3. 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

  4. Rat Genome Database Developed to support the NIH Rat Genome Project Provides genomics/genetic and phenotyping data http://rgd.mcw.edu

  5. depression

  6. 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

  7. Comparative Genomics Brings together investigators interested in the same disease but who study different models or clinical samples

  8. cM D13rat107 2.3 D13mgh13 8 D13rat88 2.2 D13rat91 2.2 D13rat101 3.6 1 D13rat127 D13rat177 3.6 D13arb10 2.5 D13rat77 D13got43 12 D13rat30 2 D13rat130 12 1.4 D13mit5 D13rat197 1.4 D13rat183 3.6 D13rat57 3.6 D13Mit4 6.5 D13rat192 Human Chr 1 Rat Chr 13 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 • Microalbuminuria 8.0 • Proteinuria 6.1 • MAP 8.4 • SAP 6.9 • DAP 8.2 3 2 4 5 1. Standing DBP LOD 1.9 2. Sitting stroke volume LOD 1.7 15 14 10 13 12 2 3 19 1 9 4 1 5 6 11 8 7 18 17 16 2

  9. Systems Biology & Physiological Genomics New types of data New ways to integrate the data Hopefully new ways to ask questions

  10. Gene Knock-out Phenotype

  11. Interactive discovery tool All physiological data present All phenotyping protocols available Ability to ask questions and run statistical analyses on the data set

  12. http://pga.mcw.edu

  13. PhysGen Home Page COMPONENTS About PGA OVERVIEW DATA Genomics Aims News Protocols Phenotyping Participants Order Research Services Strains Deliverables Education Organization Presentations Bioinformatics Strain Profile Citing Data Collaborators Education Publications Microarray Visiting Scientist LINKS Genotyping Workshops Other PGAs Atmosphere Conditioning RGD Diet Genome Scanner Phenotyping Download Analysis

  14. Where in the genome of the SS rat does hypertension map? 429,603 measurements

  15. Protective Genes

  16. 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 • 3 days • 14 days UniGene microarray Consomic SS.BN13 Liang et al. Physio Gen., 2002.

  17. 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

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