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BCM Center for Precision Medicine Models

BCM 精准医学模型中心

基本信息

批准号：
10259804
负责人：
Lindsay C Burrage
金额：
$ 198.95万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10259804
关键词：
Affect Animal Model Back Bioinformatics Caring Clinical Clinical Research Clinical Trials Collaborations Communities DNA lesion Databases Development Diagnosis Diagnostic Disease Disease model Drosophila melanogaster Genes Genetic Diseases Genome Genomics Goals House mice Human Genetics Human Genome Individual Infrastructure International Leadership Medical Genetics Medicine Mendelian disorder Modeling Modification Molecular Molecular Genetics Mus Patient Care Patients Phenotype Production Provider Rare Diseases Reporting Research Personnel Resources Structure Study models Techniques Technology Translating Translations Variant Vision body system clinical care clinical diagnostics clinically significant college design exome sequencing fly gene discovery genetic disorder diagnosis genome sequencing metabolomics multidisciplinary nonhuman primate personalized approach personalized medicine precision medicine preclinical study programs recruit therapeutic evaluation tool transcriptome sequencing translational impact translational study variant of unknown significance whole genome

项目摘要

ABSTRACT The introduction of clinical exome sequencing, whole genome sequencing, RNA sequencing, and metabolomics has transformed our ability to diagnose patients with suspected genetic disease. With the introduction of these technologies, a potential molecular DNA lesion can be identified in at least 25-30% of patients with a suspected genetic diagnosis. These technologies have also led to the discovery of hundreds of new disease genes and to phenotypic expansion within known genetic diagnoses. This continued discovery of new disease genes leads to structure, function and mechanistic discoveries that assist personalized approaches for management and therapy. However, up to 70% of patients with suspected genetic disease remain undiagnosed likely because their disease-causing variant(s) has yet to be discovered or the clinical significance of identified variants remains unclear. Precision models produced using various genome modification techniques in Drosophila melanogaster (fly) and Mus musculus (mouse) are important tools aiding in the interpretation of these variants of uncertain clinical significance and are critical for testing therapeutic paradigms. We will leverage the expertise, infrastructures, and established collaborations between the rare, Mendelian disease clinical and gene discovery programs; fly, mouse, and nonhuman primate animal modeling programs; and database infrastructure programs within the Department of Molecular and Human Genetics (DMHG) at the Baylor College of Medicine (BCM) to establish the BCM Center for Precision Medicine Modeling (BCPMM). The vision of our Center is to support local, national, and international programs and individual researchers in the development of precision models that will end the diagnostic odyssey of patients with undiagnosed, rare, and Mendelian diseases and serve as resources for pre-clinical studies investigating personalized medicine approaches to their care. We will achieve these goals by pursuing the following aims: (1) leverage existing multidisciplinary expertise within BCM to design, generate, and identify precision animal models for studies that answer clinical questions with impact on patient care; (2) conduct demonstration projects that showcase the Center’s capacity to model undiagnosed and rare diseases and to translate model organism findings back to patient care; (3) Engage human genome discovery programs, clinicians, and researchers to recruit disease-associated variant nominations for precision model studies within the Center; (4) Perform bidirectional translation of findings from precision animal models and from patient clinical studies for integration into clinical diagnostics, clinical care, or clinical trials; (5) Implement bioinformatics platforms that optimize Center disease modeling and organizational activities. Although our initial focus will build on our expertise in undiagnosed, rare, and Mendelian diseases, our long-term goal is to broaden our scope by establishing collaborations with investigators and programs focused on multigenic and common disease.

摘要