Release Date:  February 19, 1999

RFA:  HG-99-001


National Human Genome Research Institute

Application Receipt Date:  April 29, 1999


The purpose of this notice is to update the information provided to
investigators in the RFA referenced above.

A meeting organized by members of the mouse community on January 8, 1999
discussed a number of issues related to the sequencing of the mouse genome. 
While this was not an NIH-sponsored meeting, a number of issues that were
discussed will be of interest to prospective applicants for RFA HG-99-001.  A
report of the meeting, which was attended by both mouse researchers and
large-scale sequencers, outlines these issues.  The report can be found at  This is being provided by
NIH as additional information, not as an NIH policy document or a guideline
for this RFA, and the recommendations made at the Princeton meeting should not
be taken as definitive for this RFA, except as discussed below.

As described in the RFA, NHGRI staff held a Briefing about RFA HG-99-001 on
February 1, 1999. A report summarizing the discussion at that meeting can be
found at

On the basis of issues raised at these two meetings, NHGRI has decided that
several items contained in the RFA need clarification.  These are discussed
below.  Also, one additional point that must be addressed in applications
submitted in response to this RFA is described:

1.  The RFA described guidelines for applicants in terms of working draft
sequence,  but it did not explicitly discuss the production of finished
sequence.  The long-term objective of the NIH is to produce a complete,
finished sequence of the mouse genome.  In order to become a significant
contributor to this goal, a sequencing group will have to be able to
demonstrate its ability to produce finished sequence efficiently and
inexpensively. Developing and demonstrating this capability should, therefore,
be an objective from the beginning of the project, and applicants must present
plans to finish a certain amount of sequence to internationally-accepted
For new sequencing groups, the amount of finished sequence in the
first year must be a minimum of two BACs, the minimum amount needed for
quality assessment.  By the second year and thereafter, a larger portion (to
be proposed by the applicant) of the sequence produced must be finished.  In
the long run, applicants must commit to finishing any BAC or large-insert
clone that they initially sequence as a working draft.  A further discussion
of working draft and finished sequence can be found in the Report of the NIH
Briefing on this RFA posted at:

2.  The mouse C57BL6/J BAC library mentioned in the RFA is available from Dr.
Pieter de Jong at the Roswell Park Cancer Institute.

3.  The mouse research community is interested in focusing at least a portion
of initial sequencing capacity on genomic regions of particular biological
interest, and therefore in finding a mechanism by which well mapped,
biologically interesting regions may be prioritized for sequencing.  NHGRI is
currently developing a plan through which requests for sequencing of targeted
regions of the mouse genome will be peer reviewed and integrated into the
clone pipeline described in the RFA.  Grantees will need to remain flexible in
order to incorporate prioritized clones into their sequencing pipeline. 
Applicants may propose their own plan for identifying and prioritizing
interesting regions of the mouse genome for sequencing but they must be
compatible with the overall effort.

4.  The review criteria that will be used in evaluating applications have been
further clarified to include consideration of the center's ability to finish

Pilot Sequence Projects (new centers)
o  Likelihood that the sequencing strategy, data management and overall
management plans proposed will support a successful scale up of the center so
that it is likely to make a significant contribution to the completion of the
working draft and complete sequence of the mouse genome.  Specifically, the
quality of the plans to demonstrate that the center can finish data in the
first through third years will be evaluated.

Existing large-scale sequencing centers:
o Likelihood that the project will make a significant contribution to the
goals of the mouse genome project, i.e., to cover the genome with draft
sequence by 2003 and finish the sequence by 2005.  Specifically, the quality
of the plans to demonstrate that the center can finish data in the first
through third years will be evaluated.


Direct inquiries regarding programmatic issues to:

Dr. Jane L. Peterson or Dr. Bettie Graham
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

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

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