PROJECT SUMMARY OVERALL The Jackson Laboratory (JAX) Center for Precision Genetics (JCPG) will develop and disseminate new, precise mouse models that are tailored to match, as closely as possible, the disease characteristics of the afflicted patients. Through a nomination process initiated by collaborating clinical experts, patients, advocates or foundations, the JCPG Steering Committee will select and prioritize models for development and preclinical data collection. The JCPG will leverage JAX's long-established expertise in bioinformatics, mammalian genetics and disease modeling to integrate and refine existing resources, services and infrastructure to create a pipeline for development of precision mouse models for the biomedical community. These mouse models will then enter state-of-the-art animal facilities for maintenance and protection as they are prepared for distribution to biomedical and research entities worldwide. The JCPG expertise includes computational biologists, geneticists, molecular biologists, genetics technology experts and many clinical collaborators in diverse disease areas. This team not only brings together broad expertise in a range of human disease areas but also extensive ongoing experience in operating an array of large-scale public resource services. This group has a proven ability to work effectively with clinical experts to identify and delineate disease modeling needs as they emerge and then create new mouse models that serve the varied needs of the diverse set of stakeholders that need mouse models to develop new clinical treatments. The activities of the JCPG seek to achieve the following five goals. 1. Assemble and refine a comprehensive, scalable, and flexible pipeline for the generation and characterization of precision mouse models of human disease. 2. Build a data analysis and dissemination infrastructure that facilitates development of next- generation predictive models using an interactive public-facing process. 3. Accelerate the development of novel, precision therapeutics by linking patient data with new precision animal models to inform preclinical study design and generate the data needed for clinical trials. 4. Develop and deploy a robust outreach, project nomination, and project management infrastructure that expands and facilitates access to all JCPG resources by the public and biomedical community while promoting and distributing new mouse models through existing infrastructure. 5. Gain efficiencies by integrating the JCPG with other JAX programs, resources, and external- facing services and thereby establish a scalable, financially sustainable model development pipeline.

PROJECT NARRATIVE OVERALL Although potential new possibilities for human disease treatments are being discovered more rapidly than ever before, the translation of these possibilities into clinical application remains cumbersome and slow. Some of this inefficiency is due to uncertainties that arise because available animal models may not accurately and sufficiently represent details of the human disease. The pilot JAX Center for Precision Genetics (JCPG) is a multi-component Center that will build on a robust infrastructure designed to serve the biomedical community by refinement of a public-facing pipeline that operates to first identify pressing needs, and then design, create and distribute new mouse models that are specifically tailored to the disease characteristics of the patient population.