How a comprehensive digital library transforms animal model research into human medical breakthroughs
In the intricate world of biomedical research, scientists face a fundamental challenge: how to study human diseases without experimenting on humans themselves. The solution lies in model organisms—animals that share surprising genetic similarities with humans and can serve as living proxies for understanding health and disease.
The laboratory rat has been a cornerstone of physiological research, contributing to breakthroughs in cardiovascular disease, diabetes, neuroscience, and pharmacology 2 .
At its core, RGD addresses a critical need in modern biology: making sense of the overwhelming flood of genomic data generated by today's technologies. The database serves as a centralized clearinghouse where carefully curated information about genes, their functions, and their links to diseases is organized and made accessible to the scientific community 9 .
Orthologs are genes in different species that evolved from a common ancestral gene and typically retain similar functions. RGD has identified and cataloged these genetic relationships, allowing researchers to make informed predictions about human genes based on what they learn from rat studies, and vice versa 2 .
| Species | Role in Biomedical Research | Key Research Areas |
|---|---|---|
| Rat (Rattus norvegicus) | Primary physiological model | Cardiovascular disease, diabetes, neuroscience, pharmacology |
| Human (Homo sapiens) | Target species for translation | All disease areas |
| Mouse (Mus musculus) | Genetic model | Cancer, immunology, developmental biology |
| Dog (Canis lupus familiaris) | Natural disease model | Heart disease, cancer, diabetes 2 |
| Chinchilla (Chinchilla lanigera) | Specialized disease model | Otolaryngology, hearing research |
| 13-Lined Ground Squirrel (Ictidomys tridecemlineatus) | Specialized physiological model | Hibernation, metabolic regulation 2 |
Navigating the complex landscape of genetic information requires specialized tools, and RGD provides researchers with an entire workshop of them. These bioinformatics applications transform raw data into meaningful biological insights, helping scientists form and test hypotheses about gene-disease relationships.
Dedicated hubs that consolidate all available data for specific disease categories, providing immediate access to relevant genes, QTLs, rat strains, and literature references .
Object List Generator and Analyzer and Gene Annotator enable functional analysis of gene lists to determine which biological processes or diseases are overrepresented 3 .
Brings a genetics perspective to the platform, allowing researchers to explore DNA sequence variations and their potential functional consequences 2 .
Semi-automates the literature curation process by scanning PubMed abstracts and automatically identifying mentions of genes, species, and ontology terms .
Connecting Genes to Hypertension: A Hypothetical Research Journey
Dr. Rodriguez finds 1,237 rat genes associated with hypertension through various types of evidence, organized by strength of evidence .
She creates a list of all genes located within hypertension-related QTL regions for further analysis 3 .
The Multi-Ontology Enrichment Tool reveals significant enrichment for terms like "regulation of blood pressure" and "renal sodium excretion" 3 .
She discovers promising non-synonymous SNPs in the ACE2 gene across different rat strains with varying blood pressure phenotypes 3 .
Using RGD's orthology connections, she identifies human counterparts of her rat candidate genes 2 .
The Pathway Portal helps visualize how candidate genes interact within known molecular pathways relevant to cardiovascular function 3 .
| Data Category | Rat | Human | Mouse |
|---|---|---|---|
| Genes Associated with Hypertension | 1,237 | 980 | 875 |
| Hypertension QTLs | 347 | 89 | 212 |
| Strains/Models with Hypertension Phenotype | 184 | N/A | N/A |
| Variants in Hypertension-Associated Genes | 16,542 | 9,874 | 12,657 |
For scientists embarking on projects using the Rat Genome Database, having a clear map of available resources significantly enhances research efficiency.
Direct access to report pages for individual genes across multiple species, consolidating sequence data, functional annotations, and disease associations 9 .
Entry points to genomic regions associated with behavioral characteristics, disease susceptibility, and other traits 9 .
Access to data on numerous rat strains maintained and characterized in the database, helping researchers select appropriate models 9 .
This invaluable tool allows researchers to mine quantitative phenotype data across rat strains, comparing baseline measurements or examining how different strains respond to experimental interventions .
While "Rat" remains in its name, the Rat Genome Database has dramatically expanded its scope to include a menagerie of model species that collectively enhance our understanding of human biology and disease.
Centuries of selective breeding have created canine populations with reduced genetic diversity within breeds but significant differences between breeds, making them powerful models for identifying genetic contributors to traits and diseases 2 .
These animals hibernate, dramatically altering their physiology in ways that would be fatal to humans. Studying their genetic mechanisms could inform therapies for bedridden patients or astronauts 2 .
Added for its extraordinary resistance to cancer and unusual aging patterns, understanding these traits could inform new approaches to cancer prevention and treatment in humans 2 .
As we look toward the future of biomedical research, resources like the Rat Genome Database will play increasingly critical roles in advancing personalized medicine and tackling rare diseases.
RGD provides dedicated resources for rare disease research, including disease definitions, associated genes, relevant animal models, and potential therapeutic targets .
During the COVID-19 pandemic, RGD rapidly developed a Coronavirus Disease Portal that organized human genes associated with SARS-CoV-2 infection .
RGD is committed to ensuring that data are Findable, Accessible, Interoperable, and Reusable, promoting scientific reproducibility and accelerating discovery .
As sequencing technologies advance, RGD provides the contextual framework and analytical tools needed to extract meaningful biological insights for tailored treatments.
"The ultimate aim... is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions" 2 .