NAVIGATING THE TRANSLATIONAL RESEARCHER THROUGH A COMPLEX OF
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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

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Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

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


Overview

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/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

Rat Genome Database

Developed to support the NIH Rat Genome Project

Provides genomics/genetic and phenotyping data

http://rgd.mcw.edu


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

depression


Rat genome database1

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

Comparative Genomics

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


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

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

  • Proteinuria6.1

  • 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


Systems biology physiological genomics

Systems Biology & Physiological Genomics

New types of data

New ways to integrate the data

Hopefully new ways to ask questions


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

Gene Knock-out

Phenotype


Interactive discovery tool

Interactive discovery tool

All physiological data present

All phenotyping protocols available

Ability to ask questions and run statistical analyses on the data set


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

http://pga.mcw.edu


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

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


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

Where in the genome of the SS rat does hypertension map?

429,603 measurements


Protective genes

Protective Genes


Howard j jacob ph d medical college of wisconsin hmgc mcw pga mcw

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.


Summary

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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