UM1HG012077

Center for Mouse Genomic Variation at Single Cell Resolution

Any human being has, on average, 5 million single-nucleotide variants and 13 million nucleotides of insertions, deletions, and other regions present in variable copy numbers compared to the human reference genome. Together, these variants must account for all of the genetic contributions to every phenotype of that person, whether it is their height or their familial predisposition to complex diseases.

While we can quickly measure the presence of these variants in a genome, we lack the framework to understand which of the variants impact genomic function or how they interact with each other in living, breathing organisms. A core mission of the IGVF Consortium is to identify variants that impact the expression of genes using single-cell techniques and computational modeling.

Applying a single-cell genomics approach to selected diverse mouse strains can make a powerful contribution to the mission and to resources of the Consortium. Our Center for Mouse Genomic Variation at Single Cell Resolution will first use 38 mouse Collaborative Cross recombinant inbred lines that possess similar levels of sequence diversity to humans. This will help us identify variants that influence gene expression levels and chromatin accessibility at the single-nucleus level in 8 distinct tissues.

We will sequence simultaneously a subset of single-nuclei with both short-read sequencing and long-read sequencing to identify variants that impact the expression of different transcript isoforms in different cells across the different mouse strains. Additionally, we will measure the relationship of variants in these CC lines in the response of macrophages in these tissues to LPS stimulation.

The resulting resource catalogs of cell-type expression QTL, chromatin accessibility QTL, splicing QTL, and response QTL maps will be useful for IGVF modeling groups, for characterizing important variants, and for use by the wider community studying the function of these tissues. It will also aid in designing better pre-clinical models of human diseases.

Irvine University Of California

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]

Irvine, California 926970001 United States

Single Zip Code

Single-cell Profiling of Regulatory Element and Gene Activity in Relationship to Genome Function (UM1 Clinical Trial Not Allowed) (RFA-HG-20-045)

Amendment Since initial award the total obligations have increased 781% from $1,284,819 to $11,320,491.