Massively parallel characterization of variants and elements impacting transcriptional regulation in dynamic cellular systems
Active Cooperative Agreement Awarded Last action
- Award ID
- UM1HG011966
- Recipient
-
University Of Washington UEI HD1WMN6945W6
- Awarding agency
-
National Human Genome Research Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $15,138,069
Award facts
- Assistance listing
- 93.172 Human Genome Research
- Completion date 89% complete
- Originally
- Funding
-
- $14,215,226.00 Federal
- $922,843.00 Non-federal
- Place of performance
- Seattle, WA 98195, USA
Award details come from USAspending.gov.
Description
- Abstract
- A major fraction of heritability for common diseases, as well as for the penetrance and expressivity of rare diseases, partitions to distal regulatory elements in the human genome, overwhelmingly cell type-specific enhancers. However, a rate-limiting challenge for the field has been how to identify the specific variants, elements and regulated genes that mediate these effects on disease liability. Towards the overall goals of the impact of genomic variation on function (igvf) consortium, we propose to test over one million human regulatory elements or variants for their functional effects on transcriptional regulation, as well as to query over 100,000 distal regulatory elements for the gene(s) that they regulate. A first theme of our proposal is the diversity of multiplex technologies that we will employ to these ends, including massively parallel reporter assays (mpras), crisprqtl, saturation genome editing, multiplex prime editing and single cell combinatorial indexing, many of which we pioneered. A second theme is a focus on dynamic cellular systems that enable a given library of variants and/or elements to be tested across a broad range of cell types and states within a single experiment; these will include ESC-derived neuronal progenitors, cardiomyocytes, embryoid bodies, gastruloids and organoids, and in select cases, mice. A third theme involves leveraging our experience (e.g. cadd, a widely used, genome-wide catalog of variant effect predictions) to support the overarching goals of igvf. Specifically, we envision using functional measurements generated by US and others to produce well-calibrated predictions of enhancer activity and variant effects that are continuous along the branching trajectories that comprise human development. Our specific aims are as follows: (1) to perform massively parallel validation and functional characterization of candidate human enhancers in a broad range of cell type contexts. (2) to perform massively parallel characterization of human genetic variants with potential roles in human disease. (3) to contribute to a comprehensive variant-element-phenotype catalog while taking a leadership role in synergistic interactions within igvf, in the dissemination of methods, data and predictions, and in the overarching goals of the consortium.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $1,584,050 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $1,762,309 | $0 | |
| Amendment | $1,762,307 | $0 | |
| Amendment | $33,893 | $0 | |
| Amendment | $33,893 | $0 | |
| Amendment | $1,798,272 | $0 | |
| Amendment | $1,798,272 | $0 | |
| Amendment | $1,798,272 | $0 | |
| Amendment | $1,798,272 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $922,843 | $0 | |
| Original award | $922,843 | $922,843 |
Show all 14
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Regents Of The University Of California. San Francisco | $897,832 | |
| Universitätsklinikum Schleswig-Holstein | $183,662 | |
| The Regents Of The University Of California. San Francisco | $823,928 | |
| The Regents Of The University Of California. San Francisco | $33,893 | |
| Universitätsklinikum Schleswig-Holstein | $183,662 | |
| The Regents Of The University Of California. San Francisco | $823,927 |
Quick answers
Who received award UM1HG011966?
UM1HG011966 was awarded to University Of Washington by National Human Genome Research Institute (National Institutes of Health) on September 1, 2021.
How much is award UM1HG011966 worth?
$15,138,069 has been obligated on UM1HG011966: $14,215,226 in federal funding and $922,843 in non-federal funding.
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