PROJECT SUMMARY – GENETICS AND GENOMICS CORE The Genetics and Genomics Core provides advice, services and hands-on-training to Diabetes Research and Training Center (DRTC) investigators on the design and implementation of genetics and genomics studies in diabetes/obesity-related research. The Core serves not only DRTC-affiliated investigators but also diabetes investigators carrying out diabetes-related research throughout the United States and internationally. The same technology making genomic variation information accessible to everyone requires increasingly sophisticated analytic strategies that are not in the repertoire of most investigators, including the analysis and interpretation of genetic studies of diabetes and identification of diabetes-associated variants and predicted functionality of those variants. The Core also maintains the Monogenic Diabetes Registry that provides clinical and genetic data on more than 3,966 individuals from 1,971 families with a suspected genetic form of diabetes. It includes 482 with known cause MODY and 221 with neonatal as well as 29 patients with rare syndromic forms of diabetes. The Monogenic Diabetes Registry represents not only a resource that can be and is being used for longitudinal studies of these genetic forms of diabetes but is also a living biobank for cell biological and physiological studies. The expanding biobanks includes PBMCs from 21 patients and five iPSC lines. The growing awareness of the role of genetics as a primary cause of diabetes among patients and physicians has led the Core to become a national resource for genetic testing and interpretation of genetic testing results. The specific Aims of the Genetics and Genomics Core are to provide advice, training and service: 1. In the design, conduct and interpretation of genetic studies of diabetes and to make available specialized analytic tools taking advantage of cloud-based computing platforms (PrediXcan suite of analytic tools). 2. For monogenic diabetes genes mutation screening locally, regionally and nationally and consultation regarding implications of the test. This includes maintaining the Monogenic Diabetes Registry, a clinical and genetic resource and living biobank. 3. In genomic-based technologies in diabetes research, including generation of patient-specific cells (iPSCs) and animal models using BAC recombineering, transgenics, genome editing and other technologies; analysis of the epigenome and epitranscriptome and non-coding sequencing for functional effects. 4. For digital PCR services as a means to sensitively measure absolute levels of nucleic acids from tissues, cell and circulation (serum/plasma). These studies are also carried out using expertise in Cell Biology and Physiology Cores, where tissues and plasma samples often originate. The Genetics and Genomics Core integrates with the other Biomedical Research Cores by providing samples and data from patients with specific genetic forms of diabetes to the C...