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Frequently Asked Questions for Centers for Mendelian Genomics (UM1)


Questions about the Goals of the RFA

Can I propose a multi-site Center for Mendelian Genomics (CMG)?  If so, will each site be expected to carry out all of the activities that a Mendelian causal gene discovery pipeline generally entails?  Can the sites be responsible for different activities for causal gene discoveries?

Yes, a multi-site CMG may be proposed.The RFA does not require all sites to carry out exactly the same activities. However, the applicants must demonstrate to reviewers that all sites are essential components of the proposed center, and that the sites will be well integrated to function efficiently and cost-effectively despite the physical distance and additional needs for coordination.

What should I be aware of if I intend to include a foreign component in my application?

Under this RFA, a foreign component may be funded as a contractor of the lead PI.  If the foreign contractor is proposed to play a PI's role, there are two options for doing this.  1) In a Single PD/PI structure, the PD/PI needs to be in the US and the foreign contractor may be named a Co-Investigator.  2) In a multiple PD/PI structure, the Contact PD/PI needs to be in the US, and the foreign contractor may be named a PD/PI. 

This RFA limits the Total Costs.  Under this RFA, all components' direct and indirect costs will come out of the total award (up to $5M) that the lead PI will be awarded with.    

The RFA heavily emphasizes whole exome sequencing.  Can I use, for example, whole genome sequencing, RNA sequencing, or a non-sequencing genomic approach as the main causal gene discovery approach?

You may propose to use non-whole exome sequencing genomic approaches as main or complementary approaches for causal gene discovering causal genes for Mendelian conditions.  Your application should provide justification as to how the proposed approach will lead to successful discovery of causal genes.  The application should justify the proposed approach, for example, in terms of reasonable and credible advantages in cost and quality.  The most competitive applications will be those that demonstrate the highest potential to meet the research objectives with the available funds.

Does this RFA require implementation of whole genome sequencing (WGS)?

This RFA strongly encourages implementation of WGS, WHEN APPROPRIATE for the RFA goals.However, implementation of WGS is not a requirement under this RFA.

Can I subcontract out sequence production?

You may propose to subcontract out some or most of sequence production.  The capabilities of the sequence data generator should be described in the application.  In addition, you will need to demonstrate to reviewers that you understand the project design, detailed technical aspects of how the sequencing platforms perform, and implications of that for data quality, data analysis, and cost.  All applicants, whether performing sequencing in-house or contracting out, will also need to demonstrate to reviewers that they will be able to take advantage of evolving sequencing technologies in an optimal timeframe to meet the research objectives with the available funds.

Can a CMG focus on certain Mendelian disease category/categories for causal gene discoveries?       

A CMG can focus on certain Mendelian disease categories as long as a broader range of diseases, phenotypes, and genomic features is also studied.

Will this RFA support functional assays?

Under this RFA, each funded center can spend up to 2% of the total budget for functional assays for the purpose of validating causal genes and/or meeting journal requirements for publication.  NHGRI will expect the collaborators of the funded centers to be responsible for conducting most of the functional assays.   

How are the current CMGs performing?  What is their success rate?  What is the proportion of whole genome sequencing that these centers perform?

The current CMG Program was evaluated at Future Opportunities for Genome Sequencing and Beyond: A Planning Workshop for the National Human Genome Research Institute, held in July 2014.The workshop report can be found at  These centers' success rates in discovering causal genes and variants for human Mendelian conditions will be reported in an upcoming publication.  These centers currently largely use whole exome sequencing for causal gene discoveries; there is small scale whole genome sequencing for causal gene discoveries. 

Will there be other components of the NHGRI Genome Sequencing Program that the CMG should interact with?

Yes.  Applicants should consider that the overall Genome Sequencing Program (GSP) will include several Centers for Common Disease Genomics (CCDG) grantees and several CMG grantees.  In addition, NHGRI recently presented concepts to our national advisory council for a Coordinating Center and for Analysis Satellites.  NHGRI will manage all components of the GSP together as a research consortium. We will enlist a set of outside scientific consultants to help us with the management of the program.  Every grantee should be prepared to work together collaboratively on common challenges and to share information and ideas within the GSP consortium in order to increase the success of the entire program. 

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Questions about Sample Recruitment, Data Sharing and Informed Consent

Is it permissible to use samples that were collected without individual identifiers or for which individual identifiers no longer exist (so that it will not be possible to return results to clinicians or participants)?

Since this RFA focuses on the discovery of causal genes for Mendelian conditions and not on returning research results for patient care, appropriately consented samples without identifiers may be used.

Will NHGRI or NHLBI provide samples to the Centers for Mendelian Genomics?

NHGRI will not fund a separate sample solicitation effort to provide for the CMGs. The manner in which NHLBI may bring in samples for the CMGs will be announced separately.

Does NHGRI expect the recruited human samples to be broadly shared with the public? 

Widespread sharing of samples is not expected.The recruited samples are primarily intended for the use of the funded center's causal gene discoveries.Should it become necessary to bring in additional collaborators for a project (e.g., to have enough samples to meet the needs of the study), NHGRI expects the center to negotiate with the existing and potential collaborators to share samples and/or data to accomplish the study.

Do the current CMGs have a standardized consent form?  If so, could newly funded centers use the same consent forms?                                    

The current CMGs do not have a standardized consent form that is implemented across all sites.The CMGs' joint sample solicitation group has a consent form that can be shared with future CMGs.In addition, NHGRI recently revised an online informed consent resource, including sample informed consents, available at:

Is there an ELSI research component in this RFA?

This RFA does not include an ELSI research component.However, applicants should consider the overall ethical, legal and social implications related to sample selection, data use, and data release. In addition, it is possible that this program will raise issues over time that will necessitate consideration of ELSI issues.

For separate funding opportunities available through the NHGRI ELSI Research Program, please visit

Is explicit consent required for data deposition in dbGaP?

As described in the NIH Genomic Data Sharing Policy (, prospective participants should explicitly consent for genomic and phenotypic data to be used for future research purposes and to be shared broadly.For studies using data from specimens collected before the effective date of the GDS Policy (1/25/15), an assessment by an IRB, privacy board, or equivalent body is needed to ensure that data submission is not inconsistent with the informed consent provided by the research participant.NIH recognizes that in some circumstances broad sharing may not be consistent with the informed consent of some of the research participants whose data are included in the dataset.

As a rare Mendelian disease may in itself risk identification of a participant, our IRB may not approve release of genomic data to dbGaP.  Is this an acceptable project for a CMG or is sharing of the genomic data an absolute requirement?

NHGRI recognizes that some samples may not be appropriately consented for public data sharing and will defer such decisions to the local IRB.  If there is strong scientific justification as to why such samples should be used for causal gene discoveries, then a very small number of exceptions to data sharing expectations may be granted after careful consideration and negotiation with the Program staff. 

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Questions about Application Format

The Research Strategy section outlines how to apply, but it does not explicitly mention whether the application should include Specific Aims.

The application form provides for a single one-page Specific Aims section.  This will appear in the application just before the Research Strategy.  You can structure the Research Strategy the way you want to.  One option is to include one-sentence restatements of the specific aims in the Research Strategy, so the aims serve to divide the Research Strategy into separate sections covering the individual aims.  In other words, Research Strategy may be organized by aims.

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Questions about Eligibility and Funding

Is an Institution allowed to apply for either or both of these two RFAs: RFA-HG-15-001 and RFA-HG-15-002?

An institution is allowed to apply for either or both of these two RFAs. 

Note that one institution receiving awards under both RFAs could be considered as an issue of program balance when it comes time to make funding decisions (see RFA Review and Selection Process).

What types of applications is the RFA inviting? How will applications be reviewed?  How will funding decisions be made?

This RFA seeks both new and renewal applications.All applications will be reviewed by an independent panel of outside experts and evaluated against criteria stated in the RFA.  Then the applications will be subject to a second level review - including review of a proposed overall funding plan - by the National Advisory Council for Human Genome Research.  The funding criteria are also stated in the RFA.  

What is the budget cap for each application?

The applicant may propose a budget of up to $5M per year in total cost (direct costs plus F&A).Applicants may expect that budgets will be carefully negotiated prior to making funding decisions.

Will the funds be equally divided?

There may or may not be equal division of funds. The decision will be based on review results and other factors including those listed in the RFA section entitled, Review and Selection Process.

Will this RFA fund patient recruitment and sample collection activities? 

No, this RFA will not fund direct patient recruitment and sample collection activities.  It will fund efforts to identify, transfer, and utilize collected human samples for Mendelian causal gene discoveries.

Can CMG funds be spent for re-consenting?

Re-consenting may be fundable under this RFA if there is strong justification. 

Will this RFA fund sample collection activities?

No, this RFA will not fund sample collection activities.It will fund grantees to identify, transfer, and utilize existing human samples.

May I propose to use existing equipment for the proposed center?  Will new equipment be funded?

You may propose to use existing or new equipment, or a combination of both. Equipment purchases will be funded within the overall budget of the award. Note that equipment amortization should be included in the overall cost of sequence production.

Will this RFA be renewed after the four-year funding period?

This is currently unknown.For essentially all of its larger programs, NHGRI holds a strategic planning meeting about one year before decisions are made about any renewals or new FOAs.  

How much time and effort is the PI expected to commit to the proposed CMG?       

The PI is required to devote at least 1.8 person months, based on a 12-month calendar (equivalent to 15% of his/her time and effort) to the proposed CMG.If multi-PI's are proposed, then each PI is expected to commit sufficient time to serve his/her proposed role.Reviewers will be asked (see Review Criteria within the RFA) to evaluate the Management Plan section of the proposal to ensure that adequate effort and organization is proposed.

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Last Updated: March 11, 2015