The International Complex Trait Consortium

Inbred Mouse Strains Revitalized: Sharpening a Classical Genetics Tool to Add to the Complex Traits Toolbox

Molly Bogue

The Jackson Laboratory, Bar Harbor ME 04609

ABSTRACT
 
Multiple research approaches and new resources will be required to reveal the full spectrum of genetic components and environmental factors contributing to complex traits. Inbred mouse strains have been an invaluable tool for many years in genetics research. Some of the more common strains have been well characterized; however, inbred strains have not been rigorously characterized relative to one another. In this regard, inbred strains represent a virtually untapped resource. The Mouse Phenome Project capitalizes on this and the remarkable utility of inbred strains. Although homozygous at every genetic determinant, inbred strains are genetically and phenotypically diverse due to the fortuitous admixture of a number of geographically distinct subspecies. Inbred strains also provide the unique opportunity to repeatedly access a genetically fixed population, providing a powerful means to study the effects of environment on genotype.

The Mouse Phenome Project was launched to enhance the set of research tools currently available for the laboratory mouse. This international collaborative effort promotes the systematic characterization of a defined set of inbred mouse strains under controlled conditions for a wide range of phenotypes. This valuable information will help identify physiologic controls and compensatory mechanisms and will provide critical information for modeling normal and disease processes.

Through a worldwide community effort, strain characteristics data are generated and deposited in a central, web-accessible database called the MPD (Mouse Phenome Database). The MPD serves as a repository for raw data and detailed protocols, and the website provides tools for data retrieval, query, and analysis. The power of the MPD lies in the ability to store and analyze datasets contributed from any number of investigators and, moreover, to reliably compare data across all sources. Among other applications, users may identify significant mathematical correlations (based on strain means) between pair-wise measurement combinations throughout the MPD. This powerful maneuver will highlight measurements that hint of genetic codetermination, giving users an empirically-derived clue to investigate the possibility of overlapping genetic pathways and identify genes exerting pleiotropic effects.
SNPs data are being collected to assist in efforts to close the genotype-phenotype gap. This function will be available when both the SNPs and phenotypic data are of reasonable density to provide more meaningful and consistent results than currently possible. In the meantime, all SNPs data are accessible to MPD users for downloading or for reference in routine genotyping. We are committed to building the MPD to best compliment other research tools that together will provide a powerful integrated approach to dissect complex traits. Community input is needed for strategies to improve the MPD and its integration with other resources to effectively reach these goals.