INCREASING THE EFFICIENCY OF BUILDING PHYSICAL MAPS FROM CLONE 
LIBRARIES FOR GENOMIC STUDIES

RELEASE DATE:  March 21, 2002               

RFA:  HG-02-004
 
National Human Genome Research Institute (NHGRI) 
 (http://www.nhgri.nih.gov)
National Center for Research Resources (NCRR) 
 (http://www.ncrr.nih.gov)
National Institute of Mental Health (NIMH) 
 (http://www.nimh.nih.gov)

LETTER OF INTENT RECEIPT DATE:  April 23, 2002 

APPLICATION RECEIPT DATE: May 23, 2002

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations:

PURPOSE OF THIS RFA:  The NHGRI, NCRR and NIMH invite applications for 
research projects to improve the capability for rapidly and efficiently 
producing a contiguous physical map of a genome from libraries of 
genomic clones and to reduce the cost of physical mapping so that the 
NIH can afford to increase the number of genomes that will have 
physical maps available for use in genomic approaches to sequencing and 
other problems in biomedical and biological research.         
 
RESEARCH OBJECTIVES

Background

In the past three decades, a number of different vector systems have 
been developed and tested for use in constructing the large-insert 
chromosomal DNA libraries required for genomic analysis.  Over the past 
several years, the bacterial artificial chromosome (BAC) has emerged as 
the vector system of choice, although it is certainly not the only one.  
The BAC cloning system allows the isolation of genomic DNA fragments 
that are large enough (80 to >200 kilobases [kb]) to be useful for both 
genomic sequence determination and for a variety of functional studies.  
At the same time, BAC clones are less prone to artifacts than other 
available vector systems for large-fragment cloning, e.g. cosmids and 
yeast artificial chromosomes (YACs).  In this RFA, the objectives for 
developing new or improved technology to build physical maps are 
described in terms of BAC clone libraries.  However, this RFA is NOT 
limited to technology for producing BAC clone-based maps.  Any vector 
system or clone library that can be used in a highly efficient, low cost 
way to produce physical maps that may be used in complete genomic 
sequencing or other genomic studies may be proposed and will be 
considered responsive to this RFA.  

To date, the complete sequencing of all large eucaryotic genomes has 
involved large-insert clones.  The initial eucaryotic genome sequencing 
projects (including those for the S. cerevisiae, C. elegans, and A. 
thaliana genomes) were guided by carefully constructed clone-based 
physical maps.  Mapped BAC clones continue to play a critical role, 
even as whole genome shotgun sequencing has come to be an important 
component of genome-scale sequencing projects.  In the case of the 
human sequence, for example, both of the published draft sequences were 
based on a mixed strategy that involved both clone-based and whole 
genome shotgun sequence data.  Similarly, a mixed strategy is now being 
used in the sequencing of both the mouse and rat genomes, and a clone-
based component has been introduced for finishing the sequence of the 
D. melanogaster genome.  A clone map that allows sequence contigs to be 
correctly located and regions containing large repeated sequences to be 
properly assembled will be a necessity for the foreseeable future in 
the determination of a high quality, complete sequence of a large, 
repeat-rich genome.  

BAC clones and BAC libraries are also important in other types of 
studies, particularly those that require isolation of a specific region 
of a genome for analysis and genetic manipulation.  However, the 
broader use of BACs in biomedical and biological research is currently 
limited by several factors.  The NHGRI, along with the NCRR and NIMH 
have attempted to address one bottleneck, the supply of BAC libraries, 
by establishing a research network designed to expand the national 
capacity for BAC library making.  Another objective of that research 
network is to improve library construction technology and reduce the 
cost of making libraries. This effort should greatly expand the number 
of organisms, strains, and individuals for which representative BAC 
libraries will become available over the course of the next two to 
three years.  

While uncharacterized BAC libraries are useful, more extensive 
characterization of the clones in a library and organization of the 
library clones into a physical map significantly widen the range of 
uses to which the BAC clones can be put.  At present, the standard 
methods for constructing physical maps from BAC clones involve insert 
end sequencing and restriction enzyme fingerprinting.  However, as a 
few hundred thousand clones are needed to make a library that provides 
an adequate representation of a mammalian-sized genome, both techniques 
are currently relatively expensive to implement for the complete 
characterization of a large library.  For example, for 200,000 clones, 
end sequencing currently costs at least $1.5 million, while 
fingerprinting costs more than $2 million. 

Thus, in parallel with the expansion of the capacity for BAC library 
production, it would also be advantageous to increase the efficiency of 
constructing physical maps from BACs (e.g., by reducing costs) and to 
expand the capacity for doing so.  This RFA therefore solicits 
proposals for research projects that will improve the technology or 
develop new technology, reduce the cost, and ultimately increase the 
capacity for characterizing BAC libraries and using them to make 
contiguous physical maps of a genome.  

Research Objectives

Because of the present limitations on throughput and cost, NHGRI 
currently funds only the limited amount of physical mapping that is 
directly associated with, and needed for, constructing maps that are 
required for committed genomic sequencing efforts.  The purpose of this 
RFA is to increase the throughput and decrease the cost for 
characterizing a sufficient number of BACs from a library to produce a 
physical map of overlapping clones with few gaps.  If map construction 
could be made sufficiently inexpensive, it would be possible to 
construct useful maps even for genomes that were not likely to be 
sequenced soon.  Proposals that address either significant improvement 
in the efficiency of presently used methods or new and better methods 
for clone characterization and map construction will be considered to 
be responsive to this solicitation.

Improving current methods:  At present, the organization of a BAC 
library into a physical map uses both BAC-end sequence and restriction 
enzyme-based fingerprint map data.  Insufficient effort has been given 
to the optimization of either of these techniques at high throughput, 
and proposals to improve either or both approaches would be responsive 
to this RFA.  Paired BAC end sequence sets are among the data that are 
now routinely used for constructing sequence scaffolds during a genomic 
sequencing project.  The utility of a BAC-end sequence data set 
increases as the depth of the set (the number of clones for which 
paired end sequences have been determined) increases.  However, the 
depth of the BAC end sequence set is often limited by cost, as 
sequencing BAC ends is presently nearly three times more expensive than 
sequencing other substrates.  There are apparently a number of reasons 
for this difference.  It is difficult to obtain good yields of BAC DNA 
for sequencing, and the lower amounts of DNA per sample leads to a 
requirement for higher concentrations of expensive sequencing reagents.  
Furthermore, appropriate DNA preparation is difficult and automated 
preparation systems have not been developed.

As for restriction enzyme-based fingerprinting, only in the last few 
years has the methodology become reliable enough at high throughput 
levels to generate the amount of high quality data needed to build maps 
that are accurate enough and of high enough resolution to guide the 
choice of clones for sequencing.  The costs of constructing a 
fingerprint-based map have decreased somewhat recently, but remain 
high.  Additional automation may be one way to reduce this cost.  
Applications that propose research to significantly increase the 
efficiency of current BAC-end sequence and/or restriction enzyme 
fingerprinting production lines are encouraged in response to this RFA.

Developing new methods: Alternatively, completely new methods or 
strategies for constructing physical maps from large-insert clones may 
provide a better solution to decreasing the cost and increasing the 
throughput of methods for constructing physical maps.  Proposals for 
research into such new approaches are encouraged.  Applications in 
response to this RFA may address one or more than one physical mapping 
technology.  

As noted above, BAC clone libraries are specified as the reagents for 
developing new or improved technology to build physical maps in this 
RFA.  However, applications responding to this RFA are NOT limited to 
proposing technology for producing BAC-based maps.  Any clone library 
that can be used in a highly efficient, low cost way to produce a 
physical map that may be used in sequencing or other genomic studies may 
be proposed in response to this RFA.  

In order to ultimately attain the objectives of this program, a map 
generated by any new or improved technology must be utilized by a 
sequencing center as part of its sequencing strategy. NIH recognizes 
that applicants to this RFA may not necessarily be associated with a 
sequencing center that could rapidly test or implement a new 
technology.  However, to ensure that any technology developed under 
this program can actually be useful to the NHGRI sequencing program, 
the applicant must discuss the issue of how the proposed new 
technology, if successful, would be implemented.  This application 
should also include evidence from at least one of the current 
sequencing centers, of its willingness to consider implementing the new 
technology in the event that the technology were to attain its goals.  

Funds provided under this RFA are intended to support technology 
development and proof of principle for building a physical map for a 
genome of moderate to large size.  If the technology successfully 
reduces cost of physical mapping, such a proof of principle should be 
possible with the funds allocated.  Any issues relevant to the 
application of the technology to a genome of considerably larger size 
than those used to demonstrate proof of principle must be discussed.

A critical component of any high throughput production method is the 
quality of the product.  Therefore, the issues of quality assessment of 
the resources produced during the proof of principle stage by the 
proposed technology improvements must be addressed in the application.  

Finally, applicants should describe their plans for the release and 
dissemination of the physical mapping data that will be produced in the 
proof of principle stage of these research projects.  NHGRI and the 
other participating institutes strongly believe in the value of rapid 
data and materials release in the case of genomic resources.  For an 
example, the NHGRI policy on release of sequence data is available at 
http://www.nhgri.nih.gov:80/Grant_info/Funding/Statements/RFA/data_rele
ase.html.  Responses to this RFA should propose a plan for data 
release, as this will be a criterion in the review of the application. 
Appropriate data release plans will be made a condition of the awards 
made as a result of this RFA.  Applicants should also be familiar with 
the NIH statements regarding intellectual property of resources 
developed with Federal funds 
(http://www.ott.nih.gov/policy/rt_guide_final.html)

In summary, applicants for awards under this RFA:

o should address the approach(es) they propose to take to improve                    
  the technology for producing physical maps from BAC libraries     
  for use in genomic sequencing or other genomic applications,  
  such approaches may involve either significant improvements to 
  current methods for library characterization or development of  
  novel technologies,
o should explicitly describe the goals of the proposed technology  
  development effort and the milestones that will be used to  
  evaluate progress toward those goals,
o should address the issue of physical mapping costs (both current  
  and projected) and explain in detail how the proof of principle  
  phase will demonstrate the proposed technology"s potential to 
  scale for rapidly and efficiently mapping large genomes, 
o should discuss the issues involved in implementation of the new   
  technology,  
o should provide information about the applicant"s prior experience  
  in physical mapping and/or technology development for physical      
  mapping,
o should propose a quality assessment plan,
o should propose a data release plan.

MECHANISM OF SUPPORT
 
This RFA will use the NIH Cooperative Agreement (U01) award mechanism.  
This RFA is a one-time solicitation.  Future unsolicited, competing-
continuation applications based on this project will compete with all 
investigator-initiated applications and will be reviewed according to 
the customary peer review procedures. The anticipated award date is 
December 2002.
 
The NIH (U01) is a cooperative agreement award mechanism in which the 
Principal Investigator retains the primary responsibility and dominant 
role for planning, directing, and executing the proposed project, with 
NIH staff being substantially involved as a partner with the Principal 
Investigator, as described under the section "Cooperative Agreement 
Terms and Conditions of Award"  

FUNDS AVAILABLE
 
The participating Institutes and Centers intend to commit approximately 
$3 million in FY 03 to fund three to six new grants in response to this 
RFA. An applicant may request a project period of up to three years.  
Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size and 
duration of each award will also vary. Although the financial plans of 
the IC(s) provide support for this program, awards pursuant to this RFA 
are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications. At this time, it is not 
known if this RFA will be reissued.
 
ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) if your institution has any of the 
following characteristics:
	
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges,    
  hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution 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 programs.   
 
SPECIAL REQUIREMENTS 

In describing the research plan, the applicant must address the 
following issues and questions:

o Methodology - Will the proposed new or improved technology produce   
  physical maps that support different sequencing strategies, e.g.     
  clone-based sequence assemblies, whole genome shotgun assemblies?
o Usability and transportability - Will the maps that will be produced   
  with the proposed new or improved technology be widely useable? Will   
  the proposed new technology be portable to other centers? If not,   
  please explain how the new technology or the maps will be made  
  available for use by other scientists.  
o Integration into sequence or other maps - Will the maps produced  
  with the proposed new or improved technology be able to be   
  integrated? Will your new maps be easily compared to maps from other  
  organisms or to maps that have been produced by other methods? 
o Depth of clones- What depth of clones will be needed for maps  
  produced with the proposed new or improved technology?
o Cost and throughput- How do you expect the proposed new or improved  
  technology to change the cost and throughput of your maps as compared  
  to current mapping costs?
o Complexity of the genome being mapped- How will the size and  
  complexity of the genome being mapped affect the ability of the   
  proposed new or improved technology to assemble a map? 
o Propose specific, quantitative milestones for the project.  
 
I.  Cooperative Agreement Terms and Conditions of Award 

The following terms and conditions will be incorporated into the award 
statement of each cooperative agreement awarded under RFA HG-02-004 and 
will be provided to the Principal Investigator, as well as the 
appropriate institutional official, at the time of award.  The 
following special terms of award are in addition to, and not in lieu 
of, otherwise applicable OMB administrative guidelines, DHHS grant 
administration regulations at 45 CFR Parts 74 and 92 [Part 92 are 
applicable when State and local Governments are eligible to apply], as 
are other DHHS, NIH, and NIH grant administration policies: 

1.  The administrative and funding instrument used for this program 
will be the Cooperative Agreement (U01).  The cooperative agreement is 
an "assistance" mechanism (rather than an "acquisition" mechanism), in 
which substantial NIH scientific and/or programmatic involvement with 
the awardee is anticipated during the performance of the activity. 
Under the Cooperative Agreement, the NIH purpose is to support and/or 
stimulate the recipient"s activity by involvement in and otherwise 
working jointly with the award recipient in a partner role, but it is 
not to assume direction, prime responsibility, or a dominant role in 
the activity. Consistent with this concept, the dominant role and prime 
responsibility for the physical mapping technology project as a whole 
will reside with the awardee(s), although specific tasks and activities 
in carrying out the study will be shared among the awardee(s) and the 
NHGRI Program Director.

2. P.I. Rights and Responsibilities: 

The P.I. will have the primary responsibility for defining the details 
for the physical mapping project within the guidelines of RFA HG-02-004 
and for performing the scientific activities. The P.I. will agree to 
accept close coordination, cooperation, and participation of NHGRI 
staff in those aspects of scientific and technical management of the 
project as described under "NIH Program Staff Responsibilities." 

The P.I. of a physical mapping technology center will: 

o Determine experimental approaches, design protocols, set project   
  milestones and conduct experiments,
o Ensure that the technology developed for physical mapping and the    
  resources produced meet the quality standards and cost agreed upon  
  at the time of award, 
o Ensure that the technology and resources developed as part of this   
  project are made publicly available and that results are published  
  in a timely manner, 
o Ensure that the decisions about the technologies and resources   
  developed under NIH funding meet the needs of the Institute/Centers"  
  programs, as determined at the time of initiation of the project,
o Coordinate and collaborate with other U.S. and international groups   
  developing technology for producing physical maps,
o Be required to accept and implement any common guidelines and  
  procedures developed for the physical mapping technology program. 

3. NIH Program Staff Responsibilities: 

The NIH Program Director is a scientist of the NHGRI extramural staff 
who will provide normal stewardship of the award and, in addition, will 
have substantial scientific and programmatic involvement during the 
conduct of this activity through technical assistance, advice, and 
coordination.  However, the role of NIH staff will be to facilitate and 
not to direct the activities. It is anticipated that decisions in all 
activities will be reached by consensus between the Principal 
Investigator and NHGRI staff.  NHGRI will consult with NIH staff from 
the other Institutes contributing to this RFA to keep them apprised of 
progress and issues arising.  The Program Director will have the 
following substantial involvement:

o Participate in discussing research priorities, deciding optimal 
  research approaches and protocol designs (including quality 
  assessment), and contributing to any necessary adjustment of   
  research protocols or approaches,  
o Serve as liaison, helping to coordinate activities among and for the 
  awardees, including acting as a liaison to the NHGRI and the other   
  Institutes and Centers of the NIH, and as an information resource 
  about extramural genome research activities,
o Coordinate the efforts of the awardees with the BAC library makers,  
  the NHGRI sequence production program, with other U.S. large-scale  
  sequencing efforts and with the international sequencing community  
  as well as the biological community,
o Assist awardees in the development, if needed, of policies for  
  dealing with situations that require coordinated action, 
o Periodically report on the progress of the physical mapping 
  technology program to the NHGRI Director, the Sequencing Advisory 
  Panel and other NIH Institutes and Centers supporting this research, 
o Assist in promoting the availability of the resources developed in  
  the course of this project to the scientific community at large, 
o Retain the option to recommend, with the advice of the BAC Resources 
  Steering Panel, the withholding or reduction of support from any    
  cooperative agreement that substantially fails to achieve its goals   
  of improving technology according to the milestones agreed to at the  
  time of award, fails to remain state of the art in its library- 
  making capabilities, or fails to comply with the Terms and  
  Conditions of the award. 

4. Joint Responsibilities.  The awardees and Program Director will be   
   jointly responsible for:

o Discussing progress in meeting the research community"s need for   
  physical maps,

o Helping to develop uniform procedures for quality assessment of    
  resources produced,  
o Accepting and implementing the common guidelines and procedures   
  approved by the awardees, program director and CRSP. 

5. Clone Resources Steering Panel (CRSP)

The Clone Resources Steering Panel will be responsible for reviewing 
and evaluating the progress of the awards for developing and 
implementing technology for physical map construction, and the 
coordination of that program with the BAC library production and large-
scale genomic sequencing programs. The CRSP will be composed of five 
senior scientists with relevant expertise. The membership of the CRSP 
may be enlarged permanently, or on an ad hoc basis, as needed.  

At least once a year, there will be an opportunity, either in a meeting 
or by conference call, for the CRSP members to interact directly with 
the awardees.  Annually, the CRSP will make recommendations regarding 
progress of the physical mapping technology effort and present advice 
about any changes to the program that may be necessary to the Director, 
NHGRI. 

6. Arbitration Process: 

Any disagreement that may arise on scientific/programmatic matters 
(within the scope of the award), between award recipients and the NHGRI 
may be brought to arbitration.  An Arbitration Panel will be composed 
of three members:  one selected by the awardee, one selected by the 
NHGRI, and a third selected by the two prior selected members. This 
special arbitration procedure in no way affects the awardee"s right to 
appeal an adverse action that is otherwise appealable in accordance 
with NIH regulations 42 CFR Part 50, Subpart D and HHS regulation at 45 
CFR Part 16. 
 
7. Yearly Milestones: 

All awardees participating in the physical mapping technology program 
will be asked to define yearly milestones at the time of the award and 
to update these milestones annually at the anniversary date. These will 
be made a condition of the award.  In accord with the procedures 
described above, NHGRI may withhold or reduce funds for any project 
that substantially fails to meet its milestones or to maintain the 
state of the art. 
 
WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues:

Direct inquiries regarding programmatic issues to:

Dr. Jane L. Peterson 
Division of Extramural Research 
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B07 MSC 2033
Bethesda, MD 20892-2033
Telephone: (301) 496-7531 
FAX: (301) 480-2770 
E-mail: Jane_Peterson@nih.gov

Dr. John D. Harding 
Division of Comparative Medicine
National Center for Research Resources
6705 Rockledge Drive, Suite 6050, MSC 7965
Bethesda, MD 20892-7965
Telephone:  (301) 435-0776
FAX:  (301) 480-3819
E-mail:  hardingj@ncrr.nih.gov

NIMH
Dr. Hemin Chin
National Institute of Mental Health
National Institutes of Health
6001 Executive Blvd. 
Room 7190 MSC 9643
Bethesda, MD  20892-9643
Telephone: (301) 443-9869
Fax: (301) 443-9890
E-mail:  hchin@mail.nih.gov

Direct inquiries regarding review issues to:

Dr. Rudy Pozzatti
Scientific Review Administrator 
Office of Scientific Review 
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B37, MSC 2032
Bethesda, MD 20982-2032
Telephone: (301) 402-0838
Fax: (301) 435-1580
E-mail:  Rudy_Pozzatti@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Jean Cahill 
Grants Administration Branch 
National Human Genome Research Institute 
Building 31, Room B2B34, MSC 2031
Bethesda, MD 20892-2031
Telephone: (301) 402-0733 
FAX: (301) 402-1951 
E-mail: Jean_Cahill@nih.gov

LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

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.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Dr. Jane L. Peterson 
Division of Extramural Research 
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B07 MSC 2033
Bethesda, MD 20892-2033
Telephone: (301) 496-7531 
FAX: (301) 480-2770 
E-mail: Jane_Peterson@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001).  The PHS 398 is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.
 
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
photocopies, in one package to:
 
Center For Scientific Review
National Institutes Of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application 
must be sent to:

Dr. Rudy Pozzatti
Scientific Review Administrator 
Office of Scientific Review 
National Human Genome Research Institute 
National Institutes of Health 
Building 31, Room B2B37, MSC 2032
Bethesda, MD 20982-2032
Telephone: (301) 402-0838
Fax: (301) 435-1580
E-mail:  Rudy_Pozzatti@nih.gov
 
APPLICATION PROCESSING: Applications must be received by the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review.
 
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is 
essentially the same as one already reviewed. This does not preclude 
the submission of substantial revisions of applications already 
reviewed, but such applications must include an Introduction addressing 
the previous critique.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NHGRI.  

Incomplete applications will be returned to the applicant without 
further consideration.  And, if the application is not responsive to 
the RFA, CSR staff may contact the applicant to determine whether to 
return the application to the applicant or submit it for review in 
competition with unsolicited applications at the next appropriate NIH 
review cycle.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the NHGRI in accordance with the review 
criteria stated below.  As part of the initial merit review, all 
applications will:

o Receive a written critique
o Undergo a process in which only those applications deemed to have the   
  highest scientific merit, generally the top half of the applications   
  under review, will be discussed and assigned a priority score
o Receive a second level review by the National Human Genome Advisory  
  Council. 

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of your application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The scientific review group will address and consider each of these 
criteria in assigning your application"s overall score, weighting them 
as appropriate for each application.  Your application does not need to 
be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.  For example, 
you may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) SIGNIFICANCE: Does your proposal address the problem outlined in 
this RFA? How much will your proposed approach increase the efficiency 
of the constructing physical maps beyond current practices?  Will a 
larger number of physical maps for entire genomes become available for 
use in research as a result of the introduction of your proposed 
technology?

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Do you acknowledge potential problem areas and 
consider alternative tactics? Are the proposed milestones reasonable?  
Is the planning for evaluating readiness for proof of principle 
acceptable?

(3)INNOVATION:  Does your project employ novel concepts, approaches or 
methods to improve technology for characterization of BAC libraries, 
and to reduce the costs, or increase the efficiency of producing 
physical maps?  Does your project challenge existing paradigms or 
develop new methodologies or technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to 
carry out this work?  

(5) ENVIRONMENT:  Does the scientific environment in which your work 
will be done contribute to the probability of success?  Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements?  Is there 
evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

o DATA SHARING:  Are the plans for release of information about new 
technology and resources appropriate?  

o BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: April 23, 2002
Application Receipt Date:  May 23, 2002
Peer Review Date: July 2002
Council Review:  September 2002
Earliest Anticipated Start Date: December 2002

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
o Likelihood that any proposed technology development effort will lead   
  to significant improvement in the scientific quality of using BAC  
  libraries to make physical maps and/or to a reduction in the cost of   
  using BAC libraries to produce physical maps of a genome.
o General applicability of the technology to generate characterized BAC  
  libraries applicable to physical map making and to other problems in  
  genomic research.

REQUIRED FEDERAL CITATIONS 

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy 
of the NIH that women and members of minority groups and their sub-
populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating 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 clinical research should read the AMENDMENT 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_20
01.htm.  The amended policy incorporates: the use of an NIH definition 
of clinical research, updated racial and ethnic categories in 
compliance with the new OMB standards, clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398, and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable, and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS: The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 
1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for research 
involving human subjects.  You will find this policy announcement in the 
NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: 
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom of 
Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, Internet 
addresses (URLs) should not be used to provide information necessary to 
the review because reviewers are under no obligation to view the 
Internet sites.   Furthermore, we caution reviewers that their anonymity 
may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance No. 93.172_, and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.  Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 
USC 241 and 284) and administered under NIH grants policies described 
at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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