Mouse Phenome Project: understanding human biology through mouse genetics and genomics.

THE HUMAN GENOME PROJECT IS generating vast amounts of new information at breakneck speed and causing a fundamental shift in disease research. Now with the availability of a nearly complete, high-accuracy sequence of the mouse genome (7), a new and powerful paradigm for biomedical research is established. The remarkable similarity of mouse and human genomes, in both synteny and sequence, unconditionally validates the mouse as an exceptional model organism for understanding human biology. The discovery among inbred mouse strains of defined regions of high and low genomic variation inherited primarily from two ancestral Mus subspecies (6) holds great promise to make mapping and positional cloning more rapid and feasible. Haplotype maps of inbred mouse strains combined with sophisticated delineation of their phenotypic variation and gene expression patterns will enable complex trait analysis on an unprecedented scale. This issue of Journal of Applied Physiology highlights inbred strain surveys exploring phenotypic variation in drug responses [see Crabbe et al. (1) and Watters et al. (8) in this issue]. These mouse initiatives demonstrate a viable, cost-effective alternative to human research requiring family studies, population linkage analysis, or genome-wide genotyping on a multitude of individuals for association mapping.