OPPORTUNITY FOR OBTAINING DNA SEQUENCE OF REGIONS OF HIGH BIOMEDICAL INTEREST 
FROM MODEL ORGANISM GENOMES

Release Date:  March 15, 2001

NOTICE:  NOT-HG-01-002

National Human Genome Research Institute

Submission dates for 2001:  April 1, July 1 and October 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 determined to 
be of high biomedical interest.  This program was limited to BACs derived from 
the DNA of only one mouse strain, C57BL/6J.  While the program has been 
successful, several factors now warrant its expansion.  Scientists conducting 
research on other mouse strains or on other organisms have strongly indicated 
their interest in the expansion of the list of eligible organisms.  Many 
important biomedical research projects involve organisms other than the C57BL/6J 
mouse strain.  Comparative sequence analysis is an important approach to the 
identification of candidate genes, inversions, breakpoints, and conserved non-
coding sequences as candidates for cis-regulatory elements.  Many biological 
questions can 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 all species of animals, fungi, and eukaryotic 
protists. 

As in the past, there will be no cost to the investigators seeking access to 
this sequencing service; the sequencing will be done by centers that are funded 
through the 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 are 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 sequence 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 
requestor prior to public release.   All publications using these data must 
acknowledge the publicly funded effort as their source.  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 in an expeditious manner. 

2001 PROGRAM DESCRIPTION

The National Human Genome Research Institute (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 animals, fungi, and eukaryotic protists.  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.  Several of the sequencing 
centers that are participating in the Sequencing Network will dedicate a 
fraction of their sequencing capacity to this initiative.  

The program will continue 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 clone or region whose sequence is being 
requested, its importance, and its readiness to be sequenced.  A panel of peer 
reviewers will evaluate the requests and advise the NHGRI on the priority of the 
requests. Those requests judged to be of highest priority will then be chosen by 
the participating sequencing centers for inclusion in their sequencing 
pipelines, 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 eligible organisms (plants and prokaryotes are excluded).  
Requestors must also provide the BAC clone(s), if chosen, to the participating 
sequencing centers. 

SCOPE OF REQUEST

Requests may be for half-shotgun (approximately 4-fold coverage), full shotgun 
coverage (6-10-fold coverage) or finished sequence.  Investigators should 
provide appropriate justification for the requested level of coverage.  Any BAC 
sequenced from the mouse RPCI-23 library or the rat BAC library designated for 
genomic sequencing by the NHGRI Genome Sequencing Network will be finished so 
that the sequence will be maximally useful to the centers generating the 
sequence of the entire genome.  

PROCEDURE FOR SUBMITTING A REQUEST

Requests to have BAC clone(s) sequenced must be submitted electronically 
according to the following instructions. The request form 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 is included within the identified 
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 available information about the clone(s) 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’s 
sequencing pipelines can be found at: http://www.ncbi.nlm.nih.gov/genome/clone/.

6.  Requestors must agree to the following terms and conditions:

(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 (Guyer, M.  
Statement on the rapid release of genomic DNA sequence.  Genome Res. 8, 413 
(1998.).  No sequence data will be made available to the requestor prior to 
public release.

(b) Any publication using these data will acknowledge the source of the DNA 
sequence data using the following statement:  "The sequence data were generated 
by [name of sequencing center] through the NIH-funded Genome Sequencing 
Network."

(c) If BAC clone(s) sequenced through the public effort are not available 
commercially, the requestor must agree to make arrangements for the clone(s) to 
be distributed, upon request, to the scientific community in an expeditious 
manner immediately upon publication of a research paper using any or all of the 
sequence information generated through the public effort. 

The submission dates for the 2001 Program are April 1, July 1, and October 1.  
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 date. 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 the region(s) of interest is contained in the identified 
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 (http://www.ncbi.nlm.nih.gov/genome/clone/) with an indication of the 
priority recommended.  Neither the name of the investigator who requested that 
the clone(s) be sequenced nor any information about the significance of the 
region(s)contained in the clones will 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.

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 that 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 
sequence of interest, 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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