Centers for Mendelian Genomics (UM1) | Apply Online

Opportunity Summary:

The Centers for Mendelian Genomics (UM1) funding opportunity (RFA-HG-15-002) is a National Institutes of Health initiative led by the National Human Genome Research Institute (NHGRI) to support a coordinated set of genomics centers focused on accelerating gene discovery for Mendelian conditions. The program is built around large-scale, genome-wide sequencing and complementary genomic approaches, paired with strong collaborations between the funded centers and clinical or genetic researchers around the world. The overall intent is not only to identify new causal genes for rare, typically single-gene disorders and non-disease Mendelian traits, but also to strengthen the broader field by refining the end-to-end discovery process and sharing resources so that many groups can contribute to gene discovery more effectively.

A central goal of the program is to discover as many genes as possible that harbor causal genetic variants for Mendelian diseases and Mendelian traits. Practically, this means the centers are expected to run high-throughput gene discovery pipelines that can take in samples and family data, generate genome-wide sequence data (for example, exome or whole-genome sequencing), analyze and interpret candidate variants and genes, and help move findings toward validation and publication. The FOA emphasizes that these discoveries should be driven both by the centers own sequencing and analytic capabilities and by active external partnerships, recognizing that the best opportunities for novel Mendelian gene discovery often come from clinicians and investigators who can identify well-phenotyped families or individuals with rare presentations.

Another major objective is methodological and operational improvement: the program aims to increase the success rate of causal gene discovery by advancing how samples are solicited and prioritized, improving discovery strategies and study designs, and strengthening analytic methods. This includes making the pipeline more cost-effective and efficient, which matters because Mendelian gene discovery can require iterating across many families, leveraging diverse inheritance models, dealing with variable expressivity, and integrating functional or comparative evidence. The FOA signals that the funded centers should treat process improvement as part of the mission, not just a side benefit, so that the program produces practical advances in how Mendelian genomics is done at scale.

The FOA also places strong emphasis on dissemination. Beyond producing discoveries within the centers, the program is intended to enable other researchers to discover more causal genes by distributing methods, tools, and other resources developed under the award. In effect, the centers serve as hubs that not only generate results but also help standardize, document, and share approaches that the community can reuse. This could include analysis workflows, software, best practices for variant interpretation in Mendelian settings, approaches to phenotype integration, and other resources that lower the barrier for investigators who do not have large internal sequencing and bioinformatics capacity.

Coordination is a fourth pillar of the program. NHGRI highlights the need to facilitate collaborations based on common interests and to avoid unproductive duplication of gene discovery efforts across groups worldwide. This implies an expectation that centers will communicate, coordinate projects, and help align efforts so that multiple teams are not unknowingly chasing the same unresolved cases or duplicating expensive sequencing and analysis without added value. At a higher level, NHGRI intends for the program to generate insight into the methods, scale, and infrastructure required to discover all or most causal genes underlying human Mendelian conditions, moving the field toward a more complete map of Mendelian gene-disease relationships.

From an administrative and funding perspective, this opportunity uses the UM1 cooperative agreement mechanism, meaning NIH expects to have substantial programmatic involvement compared with a standard research grant. It falls under the Health activity category and the Human Genome Research CFDA number 93.172. The FOA lists an estimated total funding level of $40,000,000 and an award ceiling of $5,000,000, with no cost sharing or matching requirement. The opportunity was posted on December 12, 2014, with an original and current closing date of April 7, 2015, and an archive date of May 8, 2015.

Eligibility is broad and includes many types of U.S.-based organizations, such as public and private institutions of higher education, nonprofits (including 501(c)(3) and certain non-501(c)(3) organizations), state and local governments, tribal governments and tribal organizations, independent school districts, special district governments, small businesses, and certain for-profit organizations. The FOA also explicitly includes categories such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, and other designated serving institutions, as well as faith-based and community-based organizations and eligible federal agencies. While non-U.S. entities (foreign organizations and foreign institutions) are not eligible to apply, foreign components as defined by NIH policy are allowed, which supports the program emphasis on worldwide collaboration while keeping the applicant organization U.S.-based.

In short, this FOA is designed to fund a small number of high-capacity centers that can systematically drive Mendelian gene discovery, continuously improve the technical and operational playbook for discovery, share tools and resources with the broader community, and coordinate internationally to reduce redundancy. The endgame is not just a set of new gene discoveries, but a clearer understanding of what it will take, in infrastructure and approach, to uncover the majority of causal genes for Mendelian conditions.

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