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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