U24HG006834

Broad-Geisinger Clinical Genome Resource - Project Summary

Genomic variation underlies almost all human disease. Technological advances have made variant detection across the human genome commonplace in medical care, sparking an expansion of basic and clinical research. To accurately assess the impact of any given genomic variant on human health, clinicians and researchers must have quick, easy access to high-quality knowledge sources.

Since 2013, the Clinical Genome Resource (ClinGen) has been dedicated to creating such knowledge bases, defining the clinical relevance of genes and variants for use in medicine and research. This proposal builds upon ClinGen's successful foundation, using existing tools and approaches while developing new ones, to expand and scale our efforts. We will work closely with our colleagues submitting linked U24 grant proposals (Baylor/Stanford; University of North Carolina/Kaiser), as our work is highly integrated and synergistic for achieving our shared goals, which are embodied by our specific aims:

1) Develop and implement standards to support clinical annotation and interpretation of genes and variants;
2) Share genomic and phenotypic data between clinicians, researchers, and patients through enhanced knowledge bases for clinical and research use;
3) Enhance and accelerate expert review of the clinical relevance of genes and variants; and
4) Disseminate and integrate ClinGen knowledge and resources to the broader community.

ClinGen's approach to providing curated clinical genomic resources to aid the interpretation of individual genomes involves curating genes to understand which have been validly implicated in disease (and through what mutational mechanisms), and curating variants (and the evidence supporting claims of pathogenicity) to identify which are causal for existing disease or predictive of risk for future disease.

To address these needs, we have organized gene and variant curation expert panels by clinical domains to curate claims of gene-disease association and variant pathogenicity. In addition, we curate the dosage sensitivity for each gene to aid in the interpretation of structural variants, as well as the actionability of gene-disease pairs to guide the use of this information for determining disease risk.

To support variant interpretation, we develop standards to enable the global community to classify variants with the same rigorous standards as ClinGen. We continue to improve global data sharing of genomic knowledge through our successful partnership with ClinVar, the National Center for Biotechnology Information's repository for genomic variants and their relationships to human health, as well as through direct data sharing from patients via Genome Connect, ClinGen's patient registry. We will continue to solicit and support ClinVar submissions, with a particular focus on global and diverse data sources, allowing transparency, comparison of results, and crowdsourcing variant classification.

Finally, we disseminate ClinGen's work through multiple modalities, enabling web-based and computational data access, while educating the community on its availability and utility. ClinGen has become an invaluable community resource for genomics; continued efforts will allow us to realize the full promise for precision medicine.

The Broad Institute

NHGRI SUPPORTS THE DEVELOPMENT OF RESOURCES AND TECHNOLOGIES THAT WILL ACCELERATE GENOME RESEARCH AND ITS APPLICATION TO HUMAN HEALTH AND GENOMIC MEDICINE. A CRITICAL PART OF THE NHGRI MISSION CONTINUES TO BE THE STUDY OF THE ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) OF GENOME RESEARCH. NHGRI ALSO SUPPORTS THE TRAINING AND CAREER DEVELOPMENT OF INVESTIGATORS AND THE DISSEMINATION OF GENOME INFORMATION TO THE PUBLIC AND TO HEALTH PROFESSIONALS. THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM IS USED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM IS USED TO FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.172 - Human Genome Research

National Human Genome Research Institute (NHGRI) [HHS - NIH]

Cambridge, Massachusetts 021421027 United States

Single Zip Code

Genomic Community Resources (U24 Clinical Trial Not Allowed) (PAR-20-100)

Amendment Since initial award the total obligations have increased 404% from $4,424,870 to $22,290,986.