PROJECT SUMMARY / ABSTRACT The need to train the next generation of medical geneticists has never been more urgent. Our biggest challenge in Medicine is to handle the flood of genomic information associated with new methodologies such as next generation sequencing. The overwhelming power of these new technologies is transforming the traditional approach to medical diagnosis and functional investigations. This renewal training proposal will prepare the future generation to tackle a new reality in which: 1) genetic testing and technology continues to develop rapidly, 2) much clinical testing is done outside of the medical genetics clinic, either by other specialists or direct-to- consumer, 3) there is a growing understanding of the influence of genetics on a vast array of human disease, and 4) precision medicine based on genetic/genomic insights will transform the therapeutic landscape. Our UCLA Medical Genetics Post-Doctoral Training Program utilizes the outstanding, diverse faculty and facilities of the David Geffen School of Medicine at UCLA. The faculty of this program provides a wealth of research opportunities, varying from basic molecular biology, genomics, cell biology, stem cell research, biochemical genetics, cytogenetics, population genetics, to clinical genetics and dysmorphology. Our collaborative Faculty will remain organized around three thematic areas: Genomic Medicine, Phenotyping in the Genomic Era, and Treatment of Genetic Disease. Our current proposal includes 46 faculty members from 21 clinical and basic science departments. These applicants and their mentors are united by a common goal: excellent scholarship and leadership in human genetics research. We will provide our trainees with a broad knowledge of medical genetics and an intensive experience in genetic research over a two-year period to prepare them to become independent investigators, with a focus on linking basic science investigation in genetics to clinical medicine and thus serve as future leaders. Major strengths of the training environment include a vibrant and growing clinical genetics program with access to an ethnically varied population, state-of-the-art diagnostic laboratories in cytogenetics, biochemical genetics, and molecular genetics, including a clinical genomics center that produces exome sequencing, a wide variety of well-funded research laboratories, a longstanding training experience of faculty, a specific postdoctoral course in medical genetics, an experienced associate director for diversity in order to support the training of individuals from diverse backgrounds, including underrepresented minorities and individuals with disabilities, who can enrich our program and the field of medical genetics. While our program has a 33-year history of success, the changes implemented in the program are focused squarely on the training of future leaders using the modern technologies of genomics, and enthusiastically embraces the enormous changes that new discove...