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
http://www.nhgri.nih.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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