Mendelian Genomics Research Centers (U01 Clinical Trial Optional) | RFA HG 20 007

Frequently Asked Questions (FAQs): Mendelian Genomics Research Centers (U01 Clinical Trial Optional) - RFA-HG-20-007

1) What is this funding opportunity?

This opportunity funds the Mendelian Genomics Research Centers under a U01 cooperative agreement (Clinical Trial Optional) through the National Institutes of Health (NIH). The goal is to build a coordinated consortium that increases the share of Mendelian (single-gene) disorders for which the underlying genetic cause is known.

2) What is the central scientific aim of the program?

The central aim is to move beyond Mendelian cases where whole exome sequencing (WES) did not produce a credible candidate gene, and to develop and apply stronger discovery strategies that can still identify causal genes and variants.

3) What kinds of cases is the program trying to solve?

The program is focused on "unsolved" Mendelian cases, especially those that remain unresolved after standard WES-only approaches. The intent is to push methods, data generation, analysis pipelines, and collaborative practices to reveal disease-causing mechanisms that WES may miss.

4) Why is there an emphasis on going beyond whole exome sequencing (WES)?

WES targets protein-coding regions, but many disease-causing variants can fall outside exons or can be difficult to detect or interpret using WES-only workflows. This program emphasizes strategies that can capture and interpret genetic causes that are outside the reach of exome sequencing or are underdetected in typical WES pipelines.

5) What types of genetic variation are specifically highlighted as important to capture or interpret?

The announcement highlights variation types that can be missed or hard to interpret with WES alone, including: variants in non-coding or regulatory regions, structural variants, repeat expansions, mosaicism, complex rearrangements, and difficult-to-sequence genomic regions.

6) Is the program mainly about gene discovery or about clinical trials?

The thrust of the opportunity is gene discovery for Mendelian disease and the research approaches needed to reach diagnoses where prior sequencing efforts have not succeeded. Clinical trials are optional under this announcement.

7) What does it mean that the award mechanism is a U01 cooperative agreement?

A U01 cooperative agreement typically indicates substantial NIH scientific and/or programmatic involvement during the project. This aligns with the expectation that awardees will work in an actively managed, coordinated consortium.

8) What is meant by operating as part of a consortium?

Awardees are expected to participate in a coordinated, data-driven program structured around shared goals, shared resources, and collective progress toward Mendelian gene discovery, rather than operating as isolated single-lab projects.

9) What is the funding agency and assistance listing information?

The awarding agency is the National Institutes of Health (NIH). The opportunity is in the health category and lists CFDA number 93.172.

10) What is the maximum award amount listed for this opportunity?

The listed award ceiling is $2,000,000, suggesting support at a scale consistent with center-like operations, advanced sequencing or multi-omic strategies, and consortium participation.

11) What is the opportunity number and title?

The opportunity is RFA-HG-20-007, titled "Mendelian Genomics Research Centers (U01 Clinical Trial Optional)."

12) When was this opportunity created and what was the original closing date?

The creation date is January 13, 2020. The original closing date is July 15, 2020.

13) What type of funding is this considered?

It is categorized as discretionary funding and uses a cooperative agreement funding instrument.

14) Which U.S. government entities are eligible to apply?

Eligible applicants include state governments, county governments, city or township governments, and special district governments.

15) Are educational institutions eligible?

Yes. Eligibility includes independent school districts, public and state-controlled institutions of higher education, and private institutions of higher education. The announcement also explicitly includes several categories of minority-serving institutions, such as HBCUs, TCCUs, Hispanic-serving Institutions, Alaska Native and Native Hawaiian Serving Institutions, and AANAPISIs.

16) Are nonprofits eligible?

Yes. Eligible applicants include nonprofits with or without 501(c)(3) status (excluding higher education institutions in those nonprofit categories, since higher education has its own eligibility listing in the announcement).

17) Are for-profit organizations eligible?

Yes. For-profit organizations other than small businesses are eligible, and small businesses are also eligible.

18) Are tribal governments and tribal organizations eligible?

Yes. Eligible applicants include federally recognized Native American tribal governments and tribal organizations other than federally recognized tribal governments. The announcement also calls out Indian/Native American Tribal Governments (other than federally recognized) among additional eligible applicant types.

19) Are public housing authorities eligible?

Yes. Public housing authorities and Indian housing authorities are listed as eligible applicants.

20) Are faith-based or community-based organizations eligible?

Yes. Faith-based or community-based organizations are explicitly called out among the additional eligible applicant types.

21) Are U.S. territories or possessions eligible to apply?

Yes. U.S. territories or possessions are included among additional eligible applicant types.

22) Are federal government agencies eligible?

Yes. Eligible agencies of the federal government are listed among the additional eligible applicant types.

23) Can non-U.S. (foreign) organizations apply as the primary applicant?

No. Non-domestic (non-U.S.) entities and non-domestic (non-U.S.) institutions are not eligible to apply.

24) Can a U.S. organization apply if it has a non-U.S. component?

Non-domestic components of U.S. organizations are not eligible to apply under this announcement.

25) Are any foreign collaborations allowed at all?

Yes, foreign components (as defined in the NIH Grants Policy Statement) are allowed. This means the applicant organization must be domestic and eligible, but certain foreign project elements may be permissible if they meet NIH's definition and policy requirements for foreign components.

26) What overall outcomes is NIH trying to drive with these centers?

NIH is aiming for measurable progress in Mendelian gene discovery by improving methods and coordinated practices that increase the fraction of Mendelian disorders with known genetic causes, particularly for cases left unsolved by exome sequencing alone.

27) What kinds of approaches are encouraged by the opportunity (at a high level)?

The opportunity emphasizes methodological innovation and application, including improved data generation, strengthened analysis pipelines, and consortium-based collaboration designed to uncover causal genes and variants in unsolved Mendelian disease cases.