Mouse protein coding diversity: What's left to discover?

For over a century, mice have been used to model human disease, leading to many fundamental discoveries about mammalian biology and the development of new therapies. Mouse genetics research has been further catalysed by a plethora of genomic resources developed in the last 20 years, including the genome sequence of C57BL/6J and more recently the first draft reference genomes for 16 additional laboratory strains. Collectively, the comparison of these genomes highlights the extreme diversity that exists at loci associated with the immune system, pathogen response, and key sensory functions, which form the foundation for dissecting phenotypic traits in vivo. We review the current status of the mouse genome across the diversity of the mouse lineage and discuss the value of mice to understanding human disease. For decades, the laboratory mouse has been widely used to make fundamental discoveries about human biology, model human disease, and develop new treatments. The mouse reference genome is based on the C57BL/6J; however, researchers use a variety of strains to model human disease. Recent genome analysis has identified that the most highly variable regions of the mouse genome are enriched with genes relevant to disease and infection response. In this review, we discuss what is currently known about these regions, why they are important for human disease modelling, and what is known about their ancestral origins.