NOT-ES-01-003: IDENTIFICATION OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN DISEASE SUSCEPTIBILITY GENES

Department of Health
and Human Services (HHS)

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IDENTIFICATION OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN DISEASE SUSCEPTIBILITY GENES Release Date: March 20, 2001 NOTICE: NOT-ES-01-003 RFP NIH-ES-01-07 National Institute of Environmental Health Sciences The NIEHS is soliciting offers for a contract to: (1) establish a catalog of Single Nucleotide Polymorphisms (SNPs) in environmental response genes based on direct re-sequencing of selected genes and (2) use high-throughput sequencing technologies utilizing a national sample repository for analysis of sequence variation in the US population and to make this data available to the scientific community via centralized public databases. It is anticipated that the contractor shall re-sequence approximately 20 genes per year for a total of 60 genes over the three year term of the base contract and up to 300 genes during the potential 4 year period of the contract (if options are exercised in years 2 and 3 for re-sequencing of an additional 70 genes per year and for a 4th year to re-sequence an additional 100 genes). The Contractor shall use the DNA Polymorphism Discovery Resource (see https://www.genome.gov/Grant_info/Funding/RFA/discover_polymorphisms.html, a resource of DNA samples and cell lines from 450 U.S. Residents (Catalog Number MPDR 450) to discover DNA sequence polymorphisms and all resequencing tasks. The Contractor shall align known cDNA sequences from each candidate gene (obtained from GenBank, see http://www.ncbi.nlm.nih.gov/ or other databases such as TIGR data http://www.tigr.org with genomic sequences in order to determine the precise exon-intron structure. The Contractor shall design PCR primers to amplify each exon, intron, promoters regions, and at least 500 bps from the 5"UTR, and 500 bps from the 3"UTR from genomic DNA. The contractor shall perform actual polymorphism discovery by direct sequencing, using conventional dye-primer sequencing, on Applied Biosystems 3700 capillary machines or comparable high-throughput sequencing technology. Ultimately, the experimental data generated by the contractor for each gene shall be a table of genotypes, with one row for each of the 450 individuals, and one column for each of the polymorphisms found in that gene. The Contractor shall provide a genotype table for all discovered and validated SNPs indicating the specific region of the gene where the SNPs map, and the allele frequency for each SNP. Total number of SNPs shall be listed by functional context as: non-synonymous, synonymous, 5"UTR, 3"UTR, frameshift, splice site, intron, and promoter regions. The Contractor shall identify SNP frequencies in each re-sequenced gene. For each identifiable SNP the contractor shall provide sequence content of 1 KB on both sides of the SNP. For the purpose of this contract, "finished" means when a given gene has been re-sequenced in all 450 DNA samples and all SNPs have been identified, validated and, submitted to the dbSNP, along with their allele frequencies http://www.ncbi.nlm.nih.gov/SNP/index.html. The contractor"s facilities must be adequate to accommodate and include modern molecular biology research instrumentation, such as automated DNA sequencers and computers. The facility shall be capable of handling at least 200,000 sequencing lanes/year, with potential to increase to at least 500,000 sequencing lanes/year in subsequent years. It is expected that the Contractor shall have, at a minimum, a dedicated ABI 3700 sequencer or comparable instrumentation for this project. Award of one cost-reimbursement, completion type contract on September 30, 2001on an open competition basis is contemplated as a result of this solicitation. The estimated level of effort is for the base contract is 35,760 labor hours and 119,200 for all options. The estimated period of performance is 3 years for the base contract and 4 years if all options are exercised. Interested organizations should request either a streamlined or full RFP package. If no selection is made, a streamlined version of the RFP will be provided, which will include only the Statement of Work, deliverables and reporting requirements, special requirements, and technical evaluation criteria. After examination of these documents, any organization interested in responding to this RFP must request the entire RFP by written, telephonic ((919) 541-0416), telefax request ((919) 541-2712), or e-mail request (whaley@niehs.nih.gov). The electronic version of the CBD synopsis and the RFP (which will be available on or about April 4, 2001) will be available on the Internet at: http://www.niehs.nih.gov/dert/rcb/rfp.htm. All responsible sources may submit a proposal which shall be considered by the Agency. Expected release date of the RFP is April 4, 2001 with proposals due May 18, 2001. Requests should reference RFP NIH-ES-01-07and should be forwarded to: National Institute of Environmental Health Sciences Research Contracts Branch, DERT ATTN: Marilyn B. Whaley, Contracting Officer 79 T.W. Alexander Drive, 4401 Building P. O. Box 12874 Research Triangle Park, NC 27709 Melissa M. Pittman National Institute of Environmental Health Sciences Research Contracts Branch P.O. Box 12874 Research Triangle Park, NC 27709 919-316-4625 919-541-2712 (FAX) pittman@niehs.nih.gov

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