Genomic Mapping, Sequencing and Analysis Funding, PA-97-044

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Technologies for Genomic Mapping, Sequencing and Analysis

NIH GUIDE,Volume 26, Number 8, March 14, 1997

PA NUMBER: PA-97-044
Full Text: PA-97-044

P.T.34

National Human Genome Research Institute
National Institutes of Health

NOTE: This program announcement supersedes the following two program announcements: (PA-94-045) New and Improved Technologies for Genomic Mapping and Sequencing, NIH Guide for Grants and Contracts, Vol. 23, No. 10, March 11, 1994 and (PA-92-59) Genome Informatics Program, NIH Guide for Grants and Contracts, Vol. 21, No.12, March 27, 1992.

Keywords:
0755044
0744045

PURPOSE

The National Human Genome Research Institute (NHGRI), formerly the National Center for Human Genome Research, solicits applications for research projects to develop new technologies, and/or significantly improve existing technologies, that will facilitate and accelerate the genome mapping, sequencing and analysis goals of the Human Genome Project (HGP) in the most expeditious and economical manner. The resources produced will be used to further studies of diseases and other biological phenomena.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the federal government. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as principal investigators. Foreign organizations are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards or program project (P01) grants.

MECHANISM OF SUPPORT

Support for this program will be through research project grants (R01), FIRST awards (R29), and program project grants (P01).

RESEARCH OBJECTIVES

Background and Objectives

The NHGRI is currently engaged, along with several other federal, private, and international organizations, in a 15-year research program called the Human Genome Project (HGP). The goals are to characterize the genomes of human and selected model organisms, to develop technologies to analyze the human genome, to examine the ethical, legal, and social implications of human genetics research, and to train scientists who will be able to utilize the tools and resources developed through the HGP to pursue biological studies that will improve human health.

Significant progress toward completing these goals has been made in the past six years, with several having already been achieved. The genetic mapping goals for both the human and the mouse have been met. Progress toward the human and mouse physical mapping goals is steady, with sufficient support in place to allow the achievement of these goals ahead of schedule. The NHGRI continues, however, to be interested in improving mapping technologies, particularly for high-throughput genotyping, expansion of genetic maps to higher density, and construction of high resolution physical maps that can serve as sequencing substrates.

There has also been good progress toward completing the sequencing goals. The genomic sequence of both E. coli and S. cerevisiae have been determined (as have the sequences of several microbes that were not designated targets of the HGP), the sequence of C. elegans is expected to be finished by 1998, the complete sequence of D. melanogaster is expected to be finished shortly after the end of this century, and the genomic sequence of the human and substantial portions of the mouse genome are expected to be finished by 2005, the original target date. However, further reductions in sequencing costs and increases in throughput are needed, both to complete the human DNA sequence as inexpensively and accurately as possible, and to support the critical role that DNA sequencing will continue to play in biological research after the achievement of the goals of the HGP. Therefore, new approaches and technologies for both de novo sequencing and resequencing, as well as for optimization and integration of existing technologies, are still needed.

Given the progress to date, increased attention is now being paid to the functional analysis of genomic DNA sequence, including the identification and understanding of all coding sequences, regulatory and other functional elements in genomic DNA from both human and selected model organisms. While a few technologies for functional analysis on a genomic basis are being developed at present, additional approaches and technologies for genomic interpretation that can be applied efficiently and economically at the level of an entire genome will be required for comprehensive analyses.

Informatics will continue to play an important role in achieving all of these goals, as well as in ensuring the maintenance and accessibility of the forthcoming data. The development and application of new technologies for acquisition, management, analysis, and dissemination of genomic data are still required.

Scope

The NHGRI is interested in supporting technological advances in the following areas of research:

  1. Refining Genetic Maps;
  2. Analyzing Sequence Variation in Genomic DNA;
  3. Improving Physical Maps;
  4. Reducing the Cost of Genomic DNA Sequencing;
  5. Interpreting Genomic Sequence; and
  6. Improving Data Analysis and Management.

Each of these areas is described below and examples of research that would be appropriate under this Program Announcement are listed. These lists are not meant to be all-inclusive. Projects addressing other research problems will be considered as long as they address the current or long-term goals of the HGP. What is most important is that applicants propose to develop new technology, or to significantly improve existing technologies, that will facilitate and accelerate genomic mapping, sequencing and analysis in an expeditious and economical manner.

Technologies for Refining Genetic Maps

Currently, the best genetic maps are based on microsatellite markers. Further improvement of genetic mapping technologies, such as the development of methods for rapid genotyping and the development of new, easier-to-use markers, is needed.

Examples of research that address this goal are:

Technologies for Analyzing Sequence Variation in Genomic DNA

The first reference human genomic sequence will be completed within the next decade. This sequence will be a mosaic, being derived from several individuals whose DNA was used to construct clone libraries for sequencing. Having the reference sequence will provide experimentalists and computational biologists with a rich source of information about the basic structure of the genome. However, knowledge of sequence variation, both between individuals and between species, will be useful for the pursuit of many studies, including the genetic basis of complex phenotypes, gene function, population genetics, molecular evolution, diagnostics development, and treatment design and evaluation. Examples of research that address this goal are:

Technologies for Improving Physical Maps

Resources are in place to complete the construction of a sequence tagged site (STS) map of the human genome at a resolution of 100 kilobases. However, new conceptual approaches to constructing physical maps of the genomes of other organisms and for constructing higher resolution maps for DNA sequencing are needed. Examples of research that addresses this goal are:

Technologies for Genomic DNA Sequencing

The sequencing goals of the HGP include both the complete sequencing of the genomes of the human and specific model organisms within the projected 15 years and substantial improvement of sequencing technology. Improved technology is needed for two reasons - to rapidly and inexpensively sequence other genomes (de novosequencing) and to determine sequence variation between large numbers of individuals (re-sequencing). A wide range of technological issues require attention, including automation, system and process integration, miniaturization, parallelization, sequencing accuracy and efficient integration between physical mapping and sequencing. Examples of research that address this goal are:

Applications for large-scale sequence production will not be considered responsive to this Program Announcement. Applicants who wish to pursue large-scale production sequencing should discuss their interest with program staff.

New Technologies for the Interpretation of Genomic Sequences

Within the next decade, the genomic sequence of both the human and many non-human organisms will become available for comprehensive analysis. A major challenge will be finding all genes, regulatory elements and other functional elements in the genomic sequences. Understanding how these genetic elements function presents an ever larger challenge. To accomplish this analysis systematically and efficiently, robust, high-throughput, cost-efficient strategies and methods will be required. It can be expected that, as in the past, both experimental ("wet bench") and computational approaches will fruitfully be applied to the identification and analysis of genomic features and functions. Several technologies to monitor gene expression on a genome-wide basis are beginning to emerge and these require further development.

Additional novel approaches are needed to facilitate both biological and computational approaches to genome interpretation. Projects that address this goal should focus on technology development and be amenable to large-scale analysis and genome-wide studies. Examples of research that address this goal are:

Highest priority will be given to the development of technologies that will be used to study the human genome and/or the genomes of S.cerevisiae, C.elegans, D. melanogaster and the mouse. Technology development projects that utilize other eukaryotic organisms will be considered, but direct applicability to the analysis of the human genome must be evident.

Technologies for Data Analysis and Management

The HGP will generate mapping, sequencing and related data from many laboratories. There is a continuing need to develop and improve appropriate computer tools and information systems for the collection, storage, retrieval and distribution of these data. New methods and tools for the analysis and interpretation of genomic data are needed, as well as new data management systems. Examples of research that address this goal are:

Because of the need to provide many of these resources to the larger scientific community, applications may request funds for distribution of software and database designs and for maintenance and user-support. Such requests must be adequately justified in the application.

ADDITIONAL CONSIDERATIONS

In planning research projects, applicants are strongly encouraged to consider the following:

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol 23, Number 11, March 18, 1994.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) and will be accepted at the standard application deadlines as indicated in the application kit. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, e-mail: ASKNIH@od.nih.gov. The title and number of this program announcement must be typed in Item 2 on the face page of the application.

The completed original application and five legible copies must be delivered to:

Division of Research Grants
National Institutes of Health
6701 Rockledge Drive, Room 1040 - MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established Public Health Service referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants. NIH (or by the review group of the relevant Institute, Center, or Division), in accordance with the standard NIH peer review procedures. Following the scientific-technical review, the applications will receive a second-level review by the appropriate national advisory council.

Review Criteria
Award Criteria

Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. In addition, for applications assigned to the NHGRI will also take into consideration the following additional criteria:

In addition to the above award criteria, applications from foreign institutions must present special opportunities that are not readily available in the United States.

INQUIRIES

Inquires are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcomed. Applicants who plan to submit applications with a direct cost of $500,000 or more must obtain approval from the institute staff prior to submission of the application.

Direct inquiries regarding programmatic issues to:

Lisa D. Brooks, Ph.D.
Genome Informatics and Sequence Variation
E-mail: lisa_brooks@nih.gov

Elise Feingold, Ph.D.
Functional Analysis
E-mail: elise_feingold@nih.gov

Adam Felsenfeld, Ph.D.
Large-Scale Sequencing
E-mail: adam_felsenfeld@nih.gov

Bettie Graham, Ph.D.
Mapping and Sequence Variation
E-mail: bettie_graham@nih.gov

Jane L. Peterson, Ph.D.
Large-Scale Sequencing
E-mail: jane_peterson@nih.gov

Jeffery Schloss, Ph.D.
Sequencing Technology Development
E-mail: jeff_schloss@nih.gov

The address and telephone number for the staff listed above are:

National Human Genome Research Institute
National Institutes of Health
Building 31, Room B2B07
31 Center Drive, MSC 2033
Bethesda, MD 20892-2033
[For courier deliveries, use zip code 20814]
Phone: (301) 496-7531
Fax: (301) 480-2770

Inquiries about grants management/policy issues should be directed to:

Ms. Jean Cahill
Grants Administration Branch
National Human Genome Research Institute
Building 31, Room B2B34
31 Center Drive, MSC 2031
Bethesda, MD 20892-2031
[For courier deliveries, use zip code 20814]
Phone: (301) 402-0733
E-mail: jean_cahill@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 93.172. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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Last Reviewed: February 28, 2012