Disease Modeling Unit

6. ABSTRACT - Disease Modeling Unit (DMU) Up to 50-70% of patients with suspected genetic disease remain undiagnosed, and even when genetic testing is diagnostic, 90-95% of rare genetic disorders have no therapies. The knowledge gaps associated with undiagnosed diseases have solutions in genome modification technologies and model organism research, which can produce animal models that mimic human disease-associated variation. Among the available model organisms, Drosophila melanogaster (fly) and Mus musculus (mouse) have proven to be important tools for aiding in the interpretation of variants identified in human exome and genome data. Based on the experiences of the BCM Center for Precision Medicine Models (CPMM), fly and mouse models can successfully support new disease gene discovery by providing key data supporting variant pathogenicity, genetic mechanism, and phenotype association. Similarly, the CPMM has also demonstrated that fly and mouse models provide critical tools for discovering biomarkers of disease and performing pre-clinical assessment of new therapeutic strategies. The CPMM Disease Modeling Unit will continue to use genome modification techniques and phenotyping workflows developed by our animal modeling programs to (1) produce precision mouse and fly models that recapitulate human disease-associated variants and (2) validate variant-disease associations, identify disease mechanisms, and test putative interventions in fly and mouse models. The Unit will employ established phenotyping workflows and capabilities of BCM core facilities, as well as specialized capabilities of submitting investigators, to perform modeling studies. The Unit will use “omics” analysis, data curation, and data reporting infrastructures developed by the Bioinformatics Section. When submitted variants are selected for modeling, the Unit will work closely with the Resource and Service Section and the submitter to develop project plans, monitor project progression, and manage animal resources. Informatics tools developed by the Bioinformatics Section will be used to assist with study planning, monitoring, and data collection, and data sharing. These goals will be achieved through the following specific aims: (1) Participate in the review of variants submitted to the Center, (2) Produce and phenotype precision fly models of human disease variants, and (3) Produce and phenotype precision mouse models of human disease variants.