OPPORTUNITY FOR OBTAINING THE SEQUENCE OF DNA FROM MODEL ORGANISMS THAT ARE OF 
PARTICULARLY HIGH BIOMEDICAL INTEREST

Release Date:  November 14, 2001

NOTICE:  NOT-HG-02-002

National Human Genome Research Institute

Submission dates for 2002:  January 1, May 1 and September 1

BACKGROUND AND PURPOSE

In January 2000, the National Institutes of Health (NIH) initiated the NIH Mouse 
BAC Sequencing Program to sequence BAC clones or contigs that were evaluated to 
be of high biomedical interest.  This program was limited to only one mouse 
strain, C57BL/6J.  During the year, scientists conducting research on other 
mouse strains and other organisms approached the National Human Genome Research 
Institute (NHGRI) and several of the sequencing centers participating in the 
Program about expanding the list of eligible organisms.  Additionally, 
participants in the NIH Mouse BAC Sequencing Program suggested that comparative 
sequencing information would greatly facilitate the identification of candidate 
genes, inversions, breakpoints, and conserved non-coding sequences as candidates 
for cis-regulatory elements.  Most investigators were interested in pursuing 
biological questions that can only be addressed by having the sequence of 
specific regions, rather than the complete genomic sequence of an organism.  
Therefore, in an effort to facilitate the research interests of the larger 
biomedical research community, the NIH is expanding the NIH Mouse BAC Sequencing 
Program to include the sequencing of BAC clones from a variety of models 
organisms with the exception of plants and prokaryotes. 

There will be no cost to investigators seeking access to this sequencing 
service; the sequencing will be done by centers that have already been funded 
through the NIH Genome Sequencing Network.  As with all sequence data generated 
by the Human Genome Project, all of the sequence data generated by the NIH-
supported Genome Sequencing Network will be subject to the "Bermuda Rules."  The 
data will be rapidly released into GenBank; unfinished data will be submitted 
within 24 hours of generation of 2kb assemblies, and finished data as soon as 
completed.  In particular, under this program of sequencing regions of high 
biomedical significance, no sequence data will be made available to the 
requestors prior to public release.   All publications using these data must 
acknowledge the publicly funded effort.  In addition, if BAC clones that are 
approved for sequencing are not available commercially, the requestor must agree 
to make arrangements for the clone(s) to be distributed, upon request, to the 
scientific community approximately six months after publication. 

2002 PROGRAM DESCRIPTION

The NHGRI and its advisors, in collaboration with the Genome Sequencing Network, 
have decided to expand the list of organisms eligible for sequencing under the 
current NIH Mouse BAC Sequencing Program to include all model organisms with the 
exception of plants and prokaryotes.  This program change is intended to address 
the interest of the larger biomedical research community in obtaining sequence 
information about specific regions of genomic DNA of biomedical or biological 
significance.  At the same time, it will allow several of the participants in 
the Sequencing Network to dedicate a limited amount of their sequencing capacity 
to this initiative.  

The program will have many features of the original program.  Investigators 
interested in obtaining the sequence of a specific region will submit a short, 
Web-based application describing the region, its importance, and its readiness 
to be sequenced.  A panel of peer reviewers has been established to consider the 
requests and to advise the NHGRI on the priority of the requests. Those requests 
judged to be of highest priority will be selected by the participating 
sequencing centers subject to available capacity. 

In addition to the NIH program, the Department of Energy, the Medical Research 
Council in the United Kingdom and Genoscope in France have similar programs.  
Every effort will be made to coordinate with these agencies to avoid unnecessary 
duplication of effort.

ELIGIBILITY REQUIREMENTS

Any investigator may submit a request to have one or more BAC clones sequenced 
from one or more organisms (plants and prokaryotes are excluded), as long as the 
requestor can justify that the region to be sequenced is of high biomedical or 
biological significance.  Requestors must also be able to provide the BAC 
clone(s) to the participating sequencing centers. 

SCOPE OF REQUEST

Requests will be accepted to sequence either one BAC clone or multiple BAC 
clones from a single organism or multiple organisms (plants and prokaryotes are 
excluded).  Individuals may request half-shotgun (approximately 4-fold coverage) 
or full shotgun coverage (6-10-fold coverage) or finished sequence.  Individuals 
requesting full shotgun coverage or finished sequence must provide substantial 
justification for why the requested coverage is needed for success of the 
project.  

PROCEDURE FOR SUBMITTING A REQUEST

(NOTE:  The request form can only be accessed two weeks prior to the receipt 
date.  To view a sample request form for submission of a single BAC, go to: 
http://mouse.info.nih.gov/sampleSBacForm.asp.  To view the request form for 
submission of multiple BACs, go to: 
http://mouse.info.nih.gov/sampleMBacForm.asp) 

Requests to have BAC clone(s) sequenced must be submitted electronically 
following the instructions provided. The request form that must be used is 
available at: http://mouse.info.nih.gov.   The Web-based request must include:

1. A short description of the biomedical or biological importance of the region 
contained within the BAC clone(s) to be sequenced.

2.  Evidence that the region described lies within the requested clone(s).

3.  In the case of a BAC contig where significant map building may have been 
done, all known underlying and overlapping clones must be identified and 
evidence for the structure of the BAC contig described.

4.  Any other additional information about the clone(s), if available, such as: 
the size of the region to be sequenced, paired BAC end sequences,  genomic map 
location, available marker information; sequence information; restriction digest 
fingerprint pattern; clone instability, repeats, deletions, and problems growing 
the clone(s) and the conditions used to overcome them.

5.  Evidence that confirms that the requested region has not already been 
sequenced, and that the requested BAC is not already in the sequencing pipeline.  
Information on the status of individual BACs within the research network 
sequencing pipeline can be found at: http://www.ncbi.nlm.nih.gov/genome/clone/.

All requestors must agree to the following terms and conditions at the time of 
the submission of the request:

(a) Data will be released according to the "Bermuda Rules"(All sequence data 
generated by the publicly funded effort will be rapidly released into the public 
domain.  Unfinished data will be released within 24 hours of generation of 2 kb 
assemblies and finished data will be released as soon as completed.).  No 
sequence data will be made available to the requestor prior to public release.

(b) All publications using these data must acknowledge the publicly funded 
effort using the following statement:  "The sequence data were generated through 
the NIH-funded Genome Sequencing Network."

(c) The requester agrees to facilitate the dissemination of the clone(s), if 
requested, within six (6) months after the publication of a research paper based 
on data generated through this program.

The submission dates for the 2002 Program are January 1, May 1, and September 1.  
When the submission date falls on a holiday or a weekend, submissions will be 
accepted on the next working day.  Because of the accelerated review and 
frequent deadlines, the submission dates will not be waived for any reason.

REVIEW FOR DESIGNATION AS A PRIORITY REGION

The reviews will be conducted by a panel of biologists with a broad range of 
biomedical interests. Requests will be reviewed approximately one month after 
the submission dates listed above. The criteria for determining the relative 
priority of the requests will be:

-    biomedical or biological significance of the region contained in the clones 
identified for sequencing.  Why is this region of particular importance to the 
rapid advancement of biomedicine?  Is the genetic information in this region of 
particularly widespread relevance?; and

-   evidence that this region(s) is contained in those clones.

Requests will receive one of three designations: highest priority; moderate 
priority; and declined.

All requestors will be provided with written comments addressing the adequacy of 
the request with respect to the review criteria.  Because of the rapid review 
cycle, resubmission will be the only means for re-consideration of a request. 
There will be no limit on the number of times a request for a specific region 
can be resubmitted, but each iteration will be required to contain additional 
significant information.

POST-REVIEW AND PROGRAMMATIC CONSIDERATIONS

NHGRI staff will inform all requestors of the results of the review, 
approximately two weeks after the review meeting.  For those requests that are 
approved, it cannot be anticipated how many will be selected for sequencing 
because it will depend upon the available sequencing capacity, the number of 
BACs approved and the depth of coverage requested.  Highest priority for access 
to the sequencing facilities will be given to requests that make the most 
compelling reason(s) based on the anticipated significance of the biomedical or 
biology discovery.

Immediately following the review, all approved clones will be listed on a public 
Web site with an indication of the priority recommended.  The name of the 
investigator who requested that the clone(s) be sequenced and the information 
about the significance of the region(s)contained in the clones WILL NOT be 
given.  Once a sequencing center has chosen the BAC clone(s) for sequencing, 
that change in status will be indicated on the public Web site.  Clones to be 
sequenced will then be entered into the sequencing pipeline: 
http://www.ncbi.nlm.nih.gov/genome/clone/.

For those investigators whose BACS have been selected for sequencing, the NHGRI 
program staff listed below will discuss how to proceed with getting the relevant 
information to the sequencing center and will act as the contact point for the 
requestors during the remainder of the sequencing process. The generation of 
information from some BACs may be completed within three months of entering the 
sequencing pipeline, but some BACs may require longer periods of time.  There 
may be regions that are found to be so difficult to sequence and it will be 
necessary to archive the clone until new methods for sequencing are available.  
It is expected that such clones will be rare, but in such a case, NHGRI staff 
will notify the investigator who submitted the request.   It is also possible 
that a BAC with significant overlap to the one requested, containing the 
requested sequence, will be in the sequencing pipeline prior to the request 
entering the sequencing pipeline.  In this case, NHGRI staff will provide 
information about the expected timing for the sequencing of a particular 
project.  Requestors SHOULD NOT contact the sequencing centers directly unless 
program staff advises them to do so.  The sequencing centers will be focused on 
high throughput production of sequence data and should therefore be shielded 
from any unnecessary distractions.

INQUIRIES

Telephone and electronic inquiries are welcomed.

To discuss programmatic issues related to this program, please contact:

Bettie J. Graham, Ph.D.
National Human Genome Research Institute
National Institutes of Health
Telephone:  (301) 496-7531
E-mail:  bettie_graham@nih.gov

To discuss review issues related to this program, please contact:

Jerry Roberts, Ph.D.
National Human Genome Research Institute
National Institutes of Health
Telephone:  (301) 402-0838
E-mail:  jerry_roberts@nhgri.nih.gov

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