NOT-HG-01-002: OPPORTUNITY FOR OBTAINING DNA SEQUENCE OF REGIONS OF HIGH BIOMEDICAL INTEREST FROM MODEL ORGANISM GENOMES

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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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