Genome-wide association studies in mice

Genome-wide association studies (GWASs) have transformed the field of human genetics and have led to the discovery of hundreds of genes that are implicated in human disease. The technological advances that drove this revolution are now poised to transform genetic studies in model organisms, including mice.Until recently, most mouse genetic studies used a standard genetic cross, which has the drawback that the regions implicated in the cross are very large and contain hundreds of genes.Several recently proposed mouse GWAS strategies include those using the Hybrid Mouse Diversity Panel, the Collaborative Cross and heterogeneous and commercially available outbred stocks. Each of these strategies has advantages and disadvantages relative to the others, yet all improve resolution by an order of magnitude over the classic genetic cross.The design of GWASs in mouse strains is fundamentally different from those carried out on humans, creating new challenges and opportunities. The development of modern mouse GWAS strategies is an active research area.Using these strategies, many groups are rapidly identifying regions in the mouse genome that associate with complex traits that are relevant to human disease. This has led to the discovery of additional genes involved in human disease.Mouse GWASs have advantages over human studies in their ability to functionally characterize implicated genes to understand mechanisms. These advantages include the accessibility of relevant tissues and the ability to carry out genetic manipulations, such as knockouts, which are impossible in human studies.