The recent revolution in high-throughput sequencing and genomic technologies has enabled geneticists to rapidly map disease susceptibility to genomic regions. As a result, there has been an explosion in the number of candidate genes identified for a multitude of human conditions 
. We are now faced with the daunting task of verifying candidate disease genes, deciphering underlying mechanisms, and developing therapeutic strategies. The ability to genetically manipulate the mouse to study and model disease in vivo makes it an ideal tool to match the challenge. Current and future application of genetic tools such as somatic mosaicism, humanized rodents, and forward genetics will empower interrogation of mammalian biology and disease in the coming years. The ability to efficiently produce genetic mosaics facilitates gene analysis in somatic cells, which will reduce the time and cost that has been associated in producing germline models. Humanized rodents, which continue to evolve into better human models, can be combined with genetic mosaic tools to dissect mechanisms of human disease. Furthermore, the advent of forward genetic screening strategies like in vivo RNAi and insertional mutagenesis now allows investigators to identify novel players in mammalian disease and developmental processes. With these new tools in hand, investigators can use the mouse to rapidly identify key pathways in disease pathogenesis for targeted therapies.
It has become increasingly clear that somatic alterations, whether sequence changes or copy number variations, play a prominent role in human disease and physiology. An obvious example is cancer, where cells can be marked by hundreds of somatic mutations, many of which likely drive the progression of the disease 
. Interestingly, somatic mutations can also revert disease phenotypes, as illustrated recently in the case of ichthyosis with confetti, which has allowed for the identification of the causative mutation 
. There are also established roles for somatic mutations and the accompanying mosaicism in shaping the defense repertoire of our immune system 
and possibly creating neuronal diversity 
. Clearly, genetic mosaicism is an important mechanism driving many developmental processes, but in an aberrant context can cause disease. The advent of genetic tools, which allow us to mirror somatic mosaicism by the introduction of mutations temporally and spatially in distinct populations of cells, provide a powerful means to study the cellular interplay that shapes disease and developmental processes ().
Genetic Tools for Generating Mutant Clones and Somatic Mutagenesis in Mice.