NETWORK FOR LARGE SCALE SEQUENCING OF THE MOUSE GENOME - UPDATE Release Date: February 19, 1999 RFA: HG-99-001 P.T. National Human Genome Research Institute Application Receipt Date: April 29, 1999 PURPOSE 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 http://www.nih.gov/science/mouse/princetonmtg.html. 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 http://www.nih.gov/science/mouse/rfa_cbmgsn.html 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 standards https://www.genome.gov:80/Grant_info/Funding/Statements/RFA/quality_standard.html. 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: http://www.nih.gov/science/mouse/rfa_cbmgsn.html 2. The mouse C57BL6/J BAC library mentioned in the RFA is available from Dr. Pieter de Jong at the Roswell Park Cancer Institute. http://bacpac.med.buffalo.edu/mouse_bac.html 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 sequence: 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. INQUIRIES 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 Email: Jane_Peterson@nih.gov Email: Bettie_Graham@nih.gov 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 Email: Jean_Cahill@nih.gov


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