Department of Health and Human Services

Part 1. Overview Information

Key Dates

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

1. Part 1. Overview Information
2. Part 2. Full Text of the Announcement
   1. Section I. Funding Opportunity Description
   2. Section II. Award Information
   3. Section III. Eligibility Information
   4. Section IV. Application and Submission Information
   5. Section V. Application Review Information
   6. Section VI. Award Administration Information
   7. Section VII. Agency Contacts
   8. Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Mendelian conditions are rare, and often caused by highly penetrant mutations in single genes. Knowledge about genes that bear causal genetic variants ("causal genes") for human Mendelian diseases and non-disease traits ("Mendelian conditions") will facilitate rapid development of molecular diagnostics of Mendelian diseases, define therapeutic strategies for both Mendelian and common diseases, and lay a foundation for understanding human biology. Building on the completion of the Human Genome Project and advancement of sequencing technologies, significant progress has been made in recent years in rapidly discovering causal genes for human Mendelian conditions using DNA sequencing. The Centers for Mendelian Genomics Program (CMG Program), funded by the National Human Genome Research Institute (NHGRI) and the National Heart, Lung, and Blood Institute (NHLBI) since November 2011, is among the largest efforts to date that focus on identifying causal genes for Mendelian conditions. Initiated three years ago, this program has successfully demonstrated the power of genome-wide sequencing at scale for discovering causal genes for Mendelian conditions, contributed improvement and innovation to the approaches (for example, the phenotype driven discovery approach vs. the genotype driven approach, approaches for candidate causal gene screening, etc.), study designs, and data analysis methods for discovering causal genes, and thus made progress in enabling others to discover causal genes for more Mendelian conditions.

Despite the progress, there is still a large knowledge gap about causal genes for human Mendelian conditions. According to recent estimates, of the approximately 20,000 protein-coding genes in the human genome, which are mostly conserved across vertebrate evolution, only about 2,800 have been identified to be "causal" for Mendelian conditions so far. These causal genes have been associated with approximately 3,600 Mendelian conditions, but approximately another 3,700 Mendelian conditions have been described for which the causal genes have not yet been discovered. Additionally, more Mendelian conditions with or without known causal genes are being reported continually. Thus it is anticipated that more protein coding genes will be found to cause Mendelian conditions. Furthermore, while most of the causal variants have been identified in coding regions, it is anticipated that there may be many causal variants in non-coding regions that have yet to be discovered. With the renewed CMG Program, NHGRI intends to continue causal gene discoveries, with increased emphasis on non-coding along with coding regions. Ultimately, the effort will lay a foundation for discovering all or most of the causal genes for human Mendelian conditions.

Objectives

This FOA solicits applications for Centers for Mendelian Genomics (CMGs) with the following objectives: 1) discover as many causal genes for human Mendelian conditions as possible, 2) improve methods, costs, and efficiency to enhance the chances of success in causal gene discoveries, 3) enable others to discover more causal genes by disseminating tools, methods, and other resources that will be developed under this FOA, and 4) facilitate collaborations on gene discoveries and tool development, and avoid unproductive duplication of efforts, through worldwide coordination. These objectives are elaborated as follows.

1) Causal genes discovery. NHGRI anticipates that successful applicants to this FOA will be able to collectively associate several hundred Mendelian conditions with their causal genes using genome-wide sequencing and other complementary genomic methods. The causal genes discovered will either be novel (not previously associated with any Mendelian conditions), or previously associated with different Mendelian conditions. With the long-term goal of discovering all or most causal genes, NHGRI will consider the discovery of novel causal genes the highest priority of the CMG Program. In terms of the genetic variants to be discovered in novel and previously known causal genes, in addition to commonly found single nucleotide variants and coding region variants, applicants are encouraged to tackle the challenges to identifying structural and non-coding region variants that may be associated with Mendelian conditions. Additionally, the large number of Mendelian conditions to be studied should, collectively, encompass population diversity, span a wide spectrum of clinically and biologically informative phenotypes, and exhibit all Mendelian inheritance patterns (autosomal vs. sex-linked, dominant vs. recessive). NHGRI expects that this will lead to more insights about the range of tractability of Mendelian diseases to genomic approaches, and about the genetic features underlying Mendelian conditions as a class, e.g., pleiotropy, genetic heterogeneity, genic complexity, varied levels of penetrance, germline as well as de novo variations, mosaicisms, and other genetic features characteristic of Mendelian conditions.

Under this FOA, germline cancer projects will be considered but as a lower priority for NHGRI funding. Somatic cancer projects will not be considered for NHGRI funding.

2) Method, cost, and efficiency improvement. In order to discover a large number of causal genes, NHGRI anticipates that the funded centers will need to continually improve the discovery pipelines, but where improvements are most needed in the pipelines will vary between the centers. Examples of anticipated improvements are: effective approaches for sample solicitation; discovery approaches, study designs, and algorithms that can minimize the requirement for sample size and/or comprehensive phenotype information; processes, automation devices, standard operating procedures (SOPs), and chemistries that can reduce costs and improve efficiency overall; data analysis methods for accurate calling of candidate causal genes, rapid identification of causal genes, and analysis of sequences of difficult genomic regions; or methods for validation of the identified causal genes.

Whole Exome Sequencing (WES) has been the state-of-the-art for discovering causal genes for Mendelian conditions in recent years because of its advantages in cost and data interpretability, and because of the ability to more easily test the functional consequences of coding region variants. While this approach will likely continue to be commonly used, this FOA strongly encourages implementation of Whole Genome Sequencing (WGS), when appropriate, to enable exploration of the entire human genome for causal variants. WGS is particularly applicable when WES fails and there is reason to suspect that the underlying genetic variation lies outside of coding regions. Additionally, this FOA will consider non-sequencing genomic technologies if there is credible advantage in costs and quality for causal gene discoveries.

3) Enabling others. NHGRI will expect the funded centers to make their best effort to rapidly publish discovery results through partnerships with the collaborators, and to disseminate methods, tools, and resources developed for, e.g., sample solicitation, phenotype handling, study design, genomic data production and sharing, quality control, data analysis, or causal gene identification and validation. This knowledge will enable others to discover more causal genes, and will also benefit the larger community of researchers and clinicians who study human genetics, and rare and common diseases. Public data release will be performed in multiple ways in order to maximize the utility of the produced sequence data. Appropriately consented sequence data will be released to the database of Genotypes and Phenotypes (dbGaP) with controlled public access. Options for extrapolating useful and non-identifiable information from sequence and accompanying metadata, and providing easy access to the information, will be actively explored. Moreover, efforts will be made to enable sharing of preliminary results (e.g., candidate causal genes) among investigators who have common interests to facilitate collaboration and thereby accelerate project completion.

4) Coordination. To facilitate the collaborations mentioned above and avoid unproductive duplication of effort, the CMG Program will coordinate with other researchers and programs worldwide on Mendelian conditions to be studied and resource development. For example, the Program will facilitate international coordination by continuing its practice of posting publicly the known or suspected Mendelian conditions in its discovery pipelines. NHGRI will also encourage the development of tools for project coordination and causal gene discoveries.

Functional assays. The performance of functional assays cannot yet be scaled as effectively as sequencing. Yet, such assays are often necessary in order to validate causal genes and/or meet journal requirements for publications. Under this FOA, NHGRI will only provide limited funds for necessary functional assays (see Budget instructions in Section IV). Instead, NHGRI expects that the collaborators who provide samples to the funded centers will be responsible for conducting most of the functional assays. In the long run, NHGRI expects that such collaborations will lay the foundation for further characterization of the identified causal variants beyond what will be funded under this FOA.

Participation as part of a Research Network. Centers funded under this FOA will be expected to collaborate effectively with each other to maximize the chances of the overall success of the CMG Program (see instructions for research strategy about activities that will be coordinated across the Program). Furthermore, NHGRI plans to fund a Genome Sequencing Program Coordinating Center (GSPCC) and also potentially a separate initiative for analysis activities. These will become components of the NHGRI Genome Sequencing Research Network (GSRN), along with the Centers for Common Disease Genomics (CCDG) Program and this CMG Program. The planned GSPCC will support administrative and logistical functions across the GSRN and participate in certain data analysis activities.

Centers funded under this FOA will be expected to share appropriately consented data across the CMG program as well as across the GSRN in order to promote coordination and collaboration.

Successful applicants are likely to be asked to collaborate with other NHGRI and NIH-funded programs if common interests are identified.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Regional Organizations

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the "Apply for Grant Electronically" button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Lu Wang, Ph.D
Telephone: 301-594-7303
Fax: 301-480-2770
Email: wanglu@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

The Research Strategy must consist of the following subsections with the indicated page limits:

• Overall Research Section limited to 30 pages
• Coordination and Management Plan limited to 6 pages

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed. Up to 2% of the total budget can be devoted to functional assays for the purpose of validating causal genes and/or meeting journal requirements for publications.

The PD(s)/PI(s) funded under this FOA is (are) expected 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 project.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: the Research Strategy should consist of the two subsections as follows, uploaded as a single pdf attachment.

A. Overall Research Section

The overall research section should include plans for sample solicitation and sequencing based discovery of causal genes for human Mendelian conditions, as elaborated below. Relevant past experiences should be succinctly summarized.

Sample Solicitation

Availability of human samples appropriately consented for the proposed research and for public data release is the most likely rate-limiting step in the causal gene discovery process given the rarity of Mendelian conditions. A funded center is expected to secure an adequate supply of appropriately consented samples from clinicians and researchers worldwide for the proposed scale of causal gene discoveries. Since it may take several months for the funded centers and other potential mechanisms (see below) to develop a sample pipeline, the applicant is expected to have in house or ascertain in advance an adequate supply of appropriately consented samples of desired quality and quantity, ideally for both primary cases and additional individuals/families, for at least the first six months of operation in order to avoid any delay in genomic data generation. Information about received and ascertained samples should be summarized. The summary should include conditions (diseases and non-disease traits) and/or categories of conditions that the samples are known or suspected to represent, availability status, sample sizes, and other useful information. The applicant can, but is not required to, provide additional information about the recruited and ascertained samples in an appendix. This information should be well-organized, succinct, and only include information that can help evaluate the value of the samples for the proposed research.

For the entire funded period, the applicant should propose a plan for recruitment of collected human samples, patients and families, and/or small cohorts, through collaborations with researchers and clinicians, for known or suspected novel Mendelian conditions that collectively exhibit a wide range of clinically and biologically informative phenotypes. The plan should address soliciting strategies for the effort to be productive and cost-effective, and diversity of the targeted global regions and populations. To the extent possible, the plan should also describe how the proposed recruitment strategies would enhance the chances of success of the proposed causal gene discovery approaches and study designs. Finally, the plan must include well-supported milestones. The milestones should factor in increased demand for samples as a result of improvement of the discovery pipeline, and potential availability of additional funds from other NIH Institutes not accompanied with available samples.

Genome-wide Sequencing-based Discovery of Causal Genes for Mendelian Conditions

The plan for discovering causal genes for Mendelian conditions should describe how the chances for discovering novel causal genes will be maximized. Genome-wide sequencing based discovery should be described in relation to the main features of the current state-of-the-art discovery pipelines. If the proposed research will use a non-sequencing genomic technology, then equivalent features should be addressed and justification, for example in terms of reasonable and credible advantages in cost and/or quality, should be described.

The main features of the current state-of-the-art discovery pipelines are summarized as follows:

• Scalable process for collecting and sharing phenotype information that uses common phenotype ontologies;
• Clinical and human genetics expertise for evaluation of submitted clinical cases (phenotypes, pedigree information, etc.) of delineated or suspected Mendelian conditions as candidates to be studied for causal gene discoveries, and for interpretation of genomic data about candidate causal genes;
• Ability to design studies of a wide spectrum of Mendelian conditions that lead to success in discovering causal genes exhibiting all known Mendelian modes and a variety of genetic features;
• An automated, flexible, and scalable production and quality control pipeline for sample tracking and nucleic acid preparation, WES, and sequence data processing;
• Adequate and scalable capability for base calling, sequence alignment, and identifying and validating variants from sequence data; high variant calling sensitivity and low false discovery rate;
• Integrated bioinformatics capabilities to support production, including systems and database administration, laboratory information management system (LIMS), and data handling and deposition;
• Capability for developing, improving, and integrating new discovery approaches, methods, and technologies (e.g., robotics, chemistries, protocols, sequencing technologies) that lead to improved data quality, efficiency, and costs;
• Competitiveness in the overall cost for causal gene discoveries including sample solicitation, sample handling and quality control, whole exome capture and sequencing, data processing, and data analysis that lead to identification of causal genes, and causal gene validation;
• Flexibility of the discovery pipeline to cope with fluctuation of sample supplies;
• Ability to manage multiple research collaborations;
• Commitment to rapid release of sequence data and associated metadata to public repositories; Ability to handle and deposit sequence data and metadata from human samples, including dealing with informed consent issues related to public data deposition.

As guidance, the applicant should provide the following details in discussing these points. Where indicated, a plan should be described for the particular aspect of the proposed center.

Phenotype information handling. The applicant should describe how phenotype information will be used for the proposed research. Where it applies to the proposed discovery strategy, the applicant should describe the method/tool and ontologies that will be used for phenotype collection and sharing as appropriate.

Study design. The applicant should discuss study designs that are tailored for the variety of Mendelian inheritance modes and genetic features that causal variants may exhibit, as mentioned in the Objectives section.

Sample quality control. The applicant should describe how samples will be assessed before they are sequenced for integrity, quantity, accuracy of pedigree information and array data, etc.

Genome-wide sequencing. All sequencing and other genomic technologies proposed for the discovery of causal genes should be clearly described. The applicant should provide a description of his/her track record in using the proposed technologies and approaches, and the current status of implementation. For WES, the applicant should describe sample input requirement, genomic regions targeted and captured, levels of coverage, throughput, cost, and quality metrics. For evaluation and implementation of WGS, the plan should describe evaluation criteria (coverage, quality, costs, throughput flexibility and scalability, data interpretability, etc.); project selection criteria (e.g., failed WES projects); and a plan for scale-up if appropriate.

Method improvement and innovation. Considering the examples given in the Objectives section about where improvement may be necessary for the proposed center, but not limited to those examples, the applicant should describe past experience in method development, and planned development and implementation of improvement and innovation to the discovery pipeline.

Costs. WES cost should be reported for the past three months or most recent quarter if this information is available and projected for the first planned year of effort. A plan for reducing sequencing cost over the funded period should be proposed. The cost should be expressed as cost per exome at a quality to be stated by the applicant, and include labor, administration, management, utilities, reagents and other consumables, sequencing instruments and other large equipment (amortized over three years), informatics activities directly related to sequence production (e.g., LIMS and initial data processing), submission of data to a public database, and Indirect Costs (http://oamp.od.nih.gov/dfas/faq/indirect-costs#difference) as they relate to the above items. If WGS cost information is available, then it should be reported in the same way. A plan for reducing sequencing cost during the funded period should be proposed with milestones.

If the applicant has had sufficient experience in sequencing based discovery of causal genes for Mendelian conditions, then he/she should provide information about the average cost and range of costs for associating a Mendelian condition with a causal gene, or a unit cost for causal gene discoveries as defined by the applicant. The applicant should explain what factors have been included in the cost calculation; for example, whether or not sample ascertainment and handling costs, unsuccessful discovery efforts, discoveries of known Mendelian conditions with known causal genes (a.k.a diagnosis of a Mendelian condition), and costs for method improvement have been factored in.

Discovery pipeline management. The applicant should describe how the proposed discovery pipeline will be managed routinely. The applicant should describe how scientific and practical factors such as the following will be balanced for assigning cases to the discovery pipeline: sample quality and quantity, phenotype complexity, comprehensiveness of phenotype information, tractability to genomic approaches, value of the anticipated discovery for the goal of the program, strength of the collaborator and community for validating and further characterizing the discovered causal gene, etc. In addition, the applicant should describe how the pipeline will be managed to cope with what may be temporary increases of samples that might be provided by other sources that need to be given priorities for entering the discovery pipeline with or without accompanying funds, or decreases in sample availability.

Research collaborations. The applicant should describe a plan for managing multiple research collaborations at any given time during the funded period. The plan should describe how critical aspects of a research collaboration, e.g., communication at all stages of the collaboration, rapidly publishing the jointly made discovery, and performing data release, will be managed.

Data release. Past experiences in rapid release of sequence data and associated metadata from human samples, including dealing with informed consent issues related to public data deposition, should be summarized.

Current grantees of the CMG Program should report on progress on all forms of data release currently carried out by all CMGs.

Milestones and timelines. Quantifiable milestones including deliverables and timelines for the entire funded period should be proposed for 1) the sample solicitation plan, 2) the plan for reducing sequencing cost, and 3) projected minimum number of Mendelian conditions/condition categories and associated number of exomes and/or number of genomes to be sequenced and analyzed for causal gene discoveries. Contingency plans for dealing with potential bottlenecks should be described.

Success rates. If the applicant has had a lot of success in finding causal genes for Mendelian conditions, then he/she should provide estimates of the percentage of projects that were successful (success rates). The applicant can provide such information in categories that can best exemplify his/her discoveries (e.g., categories across all Mendelian inheritance modes, de novo mutations, sequencing with or without mapping data, etc.), and indicate the number of projects on which the estimates are based. Diagnosis of a Mendelian disease with its known causal genes and discovery of novel phenotypes for a Mendelian condition with its known causal variant(s) should not be considered as causal gene discoveries.

B. Coordination And Management Plan

Coordination

In order to maximize the chances of overall success of the CMG Program, successful applicants in response to this FOA will be required to coordinate effectively with each other and with the planned NHGRI Genome Sequencing Program Coordinating Center (GSPCC). The following are some anticipated activities that will need to be coordinated within the CMG Program: 1) publically posting and regularly updating lists of Mendelian conditions/condition categories that are in all funded centers discovery pipelines in order to avoid overlapping discovery efforts and to match samples for potential joint discovery efforts; other efforts for the same purposes; 2) joint community outreach activities such as training workshops, conference sessions, etc., to disseminate methods and tools and to identify opportunities for research collaborations; 3) efforts to harmonize, to the extent possible, the processes for obtaining informed consent; 4) joint data release activities; 5) joint publications of any collaborative research projects, resources developed under this FOA, reviews, or opinions; 6) jointly participating in the activities of the International Rare Conditions Research Consortium (IRDiRC) as a member program, and similar consortia that may arise during the course of the funded program; and 7) developing progress tracking metrics and reporting system to NHGRI and other participating NIH institutes. The applicant should describe how the proposed center will particularly contribute to any of these activities while participating in all of these. Furthermore, while these activities are largely intended for community outreach, dissemination, and international research coordination, the applicant can propose additional activities for the same purposes.

Management Plan

The applicant should propose a management plan for the proposed center. The plan should describe the organization, reporting, and communication structure within the proposed center, including the roles of key center members and decision-making processes. The plan must assure adequate personnel for 1) sample solicitation; 2) causal gene discoveries pipeline; 3) interaction with multiple collaborators on sample delivery and evaluation, study design, data analysis, causal gene identification and functional validation, transferring of phenotype and sequencing data, public data release, manuscript preparation, etc.; 4) resource sharing including public data release as appropriate; 5) coordination within the CMG Program (see above) with appointed contact persons to facilitate communications; and 6) interaction with NIH staff and scientific advisors of the Program. Recruitment and training of personnel should be discussed. Overall, the plan should discuss how the proposed organization and management structure will likely lead to success in attaining the goals of the proposed center and the CMG program.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications submitted for the January 25, 2015 due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

The Resource Sharing Plan should also include:

• 1) How methods, tools, and standard practice for identifying causal genes for Mendelian conditions that will be developed at the proposed center will be made publically available.
• 2) A data release plan. The release of sequence data and accompanying metadata to dbGaP must be consistent with the NIH Genomic Data Sharing Policy (see http://gds.nih.gov). The plan should also describe how informed consent will be designed and obtained in order to 1) allow sharing of sequence and associated metadata in dbGaP for general biomedical research rather than for narrowly defined fields (e.g., for liver cancer research, for research on bone marrow failure) for prospective samples, 2) maximize the ability to share sequence and phenotype information within research consortia, and 3) allow public release with easy access of non-identifiable information that can be extrapolated from genome sequences and accompanying metadata.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NHGRI Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030 . Applicants can submit up to 3 pages of updates to include (along with the material allowed in the Notice) relevant publications and on sample solicitation progress.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

SignificanceDoes the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is there a high likelihood that the proposed center and the resource it will create can accelerate worldwide efforts to discover causal genes for human Mendelian conditions?

Investigator(s)Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the PIs/PDs have successful experience in managing multiple collaborative projects simultaneously? Do the PIs/PDs have successful experience in genomics-based discoveries of causal genes for human Mendelian conditions?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Will the proposed center have adequate human samples available for sequencing in the initial six months of the funded period? Does the sample solicitation plan seem adequate to provide for the proposed research goals during the funded period? Is the proposed research likely to yield important lessons about what it will take to discover all or most causals genes for human Mendelian conditions? Will there be flexibility in the proposed center for genomic data generation and analysis to cope with any potential fluctuation of sample availability and increase of funds? Does the cost reduction plan seem both ambitious and plausible? Is there an adequate plan to ensure productive collaborations with sample providers and the broader community, and within the CMG Program? Will the management plan enable the proposed center and the program as a whole to meet the research and community outreach goals?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Human Genome Research Institute in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Program balance. For example, the desire to ensure that study of a diversity of rare diseases and populations, and a variety of approaches and study designs for causal gene discoveries are funded through this solicitation.
• Sample availability and ascertainment strategy for the proposed research.
• The strengths of existing scientific collaborations for validation of causal genes using functional assays.
• Track record of working effectively in large collaborative efforts or research consortia.
• Compliance with data and resource sharing policies as appropriate.
• The likelihood that the proposed center and/or available resources will contribute to and accelerate discovering causal genes for Mendelian conditions.
• The resources available that could leverage NHGRI funds towards the attainment of the Objectives of this FOA.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 [Part 92 is applicable when State and local Governments are eligible to apply], and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the awardees' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

defining the details for the funded center within the guidelines of this FOA and for performing the scientific activities. The PD(s)/PI(s) will agree to accept close coordination, cooperation, and participation of NHGRI staff in the aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities".

The PD(s)/PI(s) of a Center for Mendelian Genomics (CMG) will be responsible for the following:

• Provide the CMG's goals as requested by NHGRI staff on the number and range of Mendelian conditions/condition categories that the CMG will acquire and study to discover the causal genes for, with associated throughput, quality, and cost goals. These goals are usually requested at the outset of the award and annually thereafter, but can also be at other times.
• Determine the approaches for establishing a sample acquisition, sequencing, and data analysis and variant identification pipeline, and carrying out those efforts.
• Ensure that all milestones are met.
• Determine ways to establish and disseminate the best practices for discovering causal genes for Mendelian conditions.
• Ensure effective interaction within the CMG Program, and with the collaborators, the planned Genome Sequencing Program Coordinating Center (GSPCC), and other components of the NHGRI Genome Sequencing Research Network (GSRN).
• Coordinate and collaborate with other U.S. and international groups engaged in the genetics research and clinical practice of Mendelian conditions.
• Adhere to the NIH policies regarding intellectual property, data release and other applicable resource sharing policies that might be established during the funded period as appropriate.
• Ensure that the sequence data (alignments and variants) and/or other types of genomic data, and phenotype data, are deposited into appropriate public databases, that resources developed at the CMG are made publicly available according to NHGRI policies, and that discoveries are published in a timely manner.
• Accept and implement any procedures and guidelines developed for the CMG Program and approved by the CMG Steering Committee and NHGRI's External Scientific Panel for the GSRN.
• Submit data for quality assessment in any manner specified by the CMG Steering Committee or the planned GSPCC.
• Submit quarterly progress reports in a standard format, as agreed upon by the Steering Committee and the External Scientific Panel.
• Accept and participate in the cooperative nature of the NHGRI Genome Sequencing Research Network composed of awardees to this RFA and other components of the NHGRI Genome Sequencing Program, including:
• Within the CMG Program, coordination and collaboration between awardees as described in the Objectives section and Center Plan instructions;
• With the Centers for Common Disease Genomics that will be funded as part of the overall program;
• With the planed GSPCC or any analysis projects that NHGRI plans to solicit as part of the overall program, including being responsive to GSPCC's requests;
• Where opportunities are identified, participate in collaborations with other NIH research networks.

• Inform the Program Director of all major interactions with members of the External Scientific Panel.
• Attend CMG Steering Committee meetings.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NHGRI program staff of the CMG Program will play the role of Project Scientists and have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of the Project Scientists will be to facilitate but not to direct the activities. NHGRI Project Scientists will participate as members of the CMG Steering Committee and will have one collective vote.

• The Project Scientists will:

• Participate (with other Steering Committee members) in the group process of setting research priorities and making decisions on joint activities and standard practice of the CMG Program. The Project Scientists will assist and facilitate the group process but not direct it.
• Negotiate throughput, cost, causal gene discovery goals and timelines with the awardees, as necessary.
• Serve as liaisons between the awardees and the External Scientific Panel, the National Advisory Council for Human Genome Research, and the larger scientific community in helping the CMGs to achieve the Program goals.
• Coordinate the efforts of the CMGs with others engaged in Mendelian causal gene and variant discovery, including the awardees and program staff involved in the related NIH programs.
• Attend all Steering Committee meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• Periodically report progress to the Director of NHGRI.
• Lend relevant expertise and overall knowledge of NHGRI-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve on the External Scientific Panel.
• Serve on subcommittees of the CMG Steering Committee, as appropriate.
• Provide advice on the management and technical performance of the investigation.
• Assist in promoting the availability of the genome sequence and related resources developed at the CMGs to the scientific community at large.
• Participate in data analysis, interpretations, and where warranted, co-authorship of the publication of results of studies funded under this FOA.
• Additionally, an agency program official or institute program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as the NIH Project Scientist.

Areas of Joint Responsibility:

A Steering Committee will serve as the main governing board of the CMGs. The Committee membership will include the PD(s)/PI(s) of each awarded cooperative agreement, the NHGRI Project Scientists and staff representatives of other NIH funding institutes. The Steering Committee Chair will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions.

The Steering Committee will:

• Develop uniform procedures and policies necessary to meet the goals of the CMG Program, for example, SOPs for data release; metrics to measure data production, costs, and progress in finding novel causal genes, etc. Adoption of procedures and policies will require concurrence by the External Scientific Panel.
• Establish joint goals for sample solicitation and causal gene discoveries and discuss progress in meeting these goals.
• Make decisions about the activities such as joint data release for easy access, conducting workshops, etc.
• Each full member (limited to one person per awarded center) will have one vote except NHGRI Project Scientists, who will have one collective vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
• Another area of joint responsibility is that NHGRI and the grantees will work with and provide information to the External Scientific Panel. The External Scientific Panel will be responsible for approving the CMG Program and individual CMGs' annual goals. The External Scientific Panel will also be responsible for reviewing and evaluating the CMG Program and individual CMGs' progress toward the goals. The External Scientific Panel will provide recommendations to the Director, NHGRI, about continued support of the components of the GSRN Network. The External Scientific Panel is composed of six to ten senior scientists with relevant expertise who are not PD(s)/PI(s) of a cooperative agreement involved in the GSRN. The membership of Scientific Advisory Panel may be enlarged permanently, or on an ad hoc basis, as needed. Subdivisions in the Scientific Advisory Panel may be created to better manage the growing number of components of the GSRN.

• The External Scientific Panel will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the Panel members to interact directly with the awardees. The External Scientific Panel will make recommendations regarding progress of the GSRN and present advice about changes, if any, which may be necessary in the GSRN to the Director of NHGRI.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought, at the request of an awardee, to Dispute Resolution. A Dispute Resolution Panel will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in a case where only one awardee has the disagreement, the first member may be chosen by the individual awardee. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. In addition to the reports above, awardees will be required to provide quarterly reports in standardized format on production, cost, and progress, as determined by NHGRI in concert with External Scientific Advisors to the program.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

Scientific/Research Contact(s)

Lu Wang, Ph.D
National Human Genome Research Institute (NHGRI)
Telephone: 301-594-7303
Email: [email protected]

Weiniu Gan, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: [email protected]

Peer Review Contact(s)

Rudy Pozzatti, Ph.D
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8739
Email: [email protected]

Financial/Grants Management Contact(s)

Cheryl Chick
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: [email protected]

Gayle Jones
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0140
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.