RESEARCH NETWORK FOR LARGE SCALE SEQUENCING OF THE HUMAN GENOME - CHANGE OF SCOPE

Release Date:  September 29, 1998

RFA:  HG-98-002

P.T.

National Human Genome Research Institute

Application Receipt Date:  December 10, 1998

PURPOSE

The purpose of this notice is to inform investigators who have expressed an
interest in applying for the above-referenced RFA that the National Human Genome
Research Institute (NHGRI) is revising the scope of the RFA in light of recent
advice from the National Advisory Council for Human Genome Research (NACHGR). 
The NACHGR has approved a new NIH-DOE plan for the Human Genome Project (HGP) in
the U.S. for the years 1999-2003.  (The full NIH-DOE five-year plan will be
published in the October 23, 1998 issue of Science.)  The new plan calls for the
completion of a finished, high quality human DNA sequence by 2003;  in addition,
the plan calls for generation of a 'working draft' of the sequence � consisting
of at least 90% coverage and at least 99% accuracy � by 2001.  The sequence data
on which the working draft will be based will be held to quality standards aimed
at ensuring that the data can later be directly used in assembling finished
genomic sequence.  Therefore, assembly of the working draft should not create
loss of efficiency or increases in overall cost.  Finally, the plan also calls
for finishing one-third of the human sequence by 2001, focusing on gene-rich
regions of the genome.

Investigators who plan to respond to this RFA must address the new NHGRI
sequencing goals (available at URL:
http://www.nhgri.nih.gov/DER/Announcements/goals.html)in their applications.
Applications for large-scale sequencing centers should focus on production of
finished sequence, but may also propose to generate additional draft-quality
sequence in their research plan.

The primary objective of the specialized centers remains contributing, in any of
a variety of ways, to the completion of the human DNA sequence by providing
flexibility, capabilities or services that the sequence production centers
cannot.  The following are examples of activities that would be appropriate for
specialized sequencing projects in light of the new goals for the genome project: 
producing finished and draft-quality sequence, albeit at a smaller scale than the
production centers; collaborating with another sequencing center by finishing
some portion of the draft-quality data being produced by the collaborating center
or by producing draft sequence for finishing by the collaborator.  As stated in
the original RFA, investigators may also propose to organize specialized
sequencing centers around the sequencing of difficult regions of the genome or
the testing of a new technology or strategy.

Award criteria for the large-scale sequencing centers and specialized sequencing
centers have been revised as follows:

Awards will be made on the basis of scientific and technical merit as determined
by peer review, including the significance of the projected contribution toward
meeting the NHGRI program goals of:  contributing to the completion of the
finished, high quality human DNA sequence by the year 2003, generating a draft-
quality sequence covering at least 90% of the human genome and at least 99%
accuracy by 2001, and completing finished, high quality sequence representing
one-third of the human genome by 2001.  Award decisions will also take into
account program needs and balance; adherence to NHGRI policies on human subjects,
data release and intellectual property; and the availability of funds.

It is expected that, under the terms of the Cooperative Agreement as specified
in the RFA, there will be effective collaboration and coordination amongst the
successful applicants. Applicants should address in the application, the role
they will play in the Cooperative Agreement.

Funds Available:  It is anticipated that as much as $120 million may be available
for support of the Research Network in FY 1999.  The funding level will be
dependent upon the availability of funds.

Quality Control Center:  NHGRI has determined that it will not accept
applications for a quality control center as part of this RFA, but will instead
issue an RFP for a contract to perform sequence quality assessment in the near
future.

Review Schedule:  In response to the accelerated timetable for completion of the
human genome sequence described in the new NIH-DOE 5-year plan, the NACHGR
advised NHGRI to accelerate the review and funding of applications submitted by
groups that have already demonstrated the capability to contribute large amounts
of finished, high quality human DNA sequence.  Therefore, applications from
groups that have sequenced and deposited in a public database by December 10,
1998 at least 15 Mb of completed genomic sequence (in contigs greater than 30,000
bp) will be reviewed on an accelerated timetable and considered by the NACHGR at
its February 1999 meeting.  Approximately one-half of the funds available for the
RFA will be available to fund these projects after the February Council meeting.
All other applications for large-scale sequencing centers and specialized
sequencing centers will be reviewed on the timetable outlined in the original
RFA, but should be submitted for the December 10, 1998 receipt date, not October
9, 1998.  In July 1999, the remaining funds will be used to support additional
efforts that can sequence human genomic DNA rapidly and efficiently, or to
increase support for the most efficient production efforts.

Quality Control Exercise for RFA:  As announced in the RFA, as part of the
review of the applications, NHGRI will conduct a quality control exercise for
all applicants who have deposited completed sequence in GenBank.  This
exercise will commence November 1, 1998.  NHGRI staff will contact those who
have already submitted letters of intent to discuss the details of the quality
control exercise.

Web-based Progress Report:  The set of questions that must be addressed by
applicants as part of their progress report of their applications has been
revised and is posted at URL: 
http://www.nhgri.nih.gov/DER/Announcements/progress_reports.html.  A new
addition to this set is a format for presenting sequencing costs which must be
used to report sequencing costs for the previous year and for the years of
support requested in the application.  The budget should also be submitted in
the usual format requested in the Form PHS 398.

INQUIRIES

Direct inquiries regarding programmatic issues to:

Dr. Jane L. Peterson or Dr. Adam Felsenfeld
Division of Extramural Research
National Human Genome Research Institute
38 Library Drive, Room 614, MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 496-7531
FAX:  (301) 480-2770
Email:  Jane_Peterson@nih.gov
        Adam_Felsenfeld@nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Jean Cahill
Grants Management Office
National Human Genome Research Institute
38 Library Drive, Room 613, MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 402-0733
FAX:  (301) 402-1951
Email:  Jean_Cahill@nih.gov

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