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A -- High Throughput Genotyping for Studying the Genetic Contributions to Human Disease

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541710 — Research and Development in the Physical, Engineering, and Life Sciences
Contracting Office
Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, Contracts Operations Branch 6701 Rockledge Dr RKL2/6100 MSC 7902, Bethesda, MD, 20892-7902
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The Center for Inherited Disease Research (CIDR) is a program dedicated to providing high quality, high throughput genotyping in support of efforts to locate and identify genes responsible for human disease. The identification of the locations of genes that predispose to or are responsible for a variety of human diseases will greatly benefit the programs of the National Institutes of Health. When the chromosomal localizations of genes contributing to such diseases are in hand, the genes likely to be involved can be identified and the functioning of their gene products in normal and disease states can be studied. New DNA-based diagnostic methods can be developed. Ultimately, identification of the genes can illuminate the biochemical and physiological pathways that have become deranged in these disorders and thus provide insights that may be crucial to developing both preventive and therapeutic interventions, thereby improving the public health. CIDR is a program established and supported by twelve NIH Institutes: National Human Genome Research Institute (NHGRI), National Cancer Institute, National Institute of Dental and Craniofacial Research, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, National Eye Institute, National Institute of Environmental Health Sciences, National Institute on Aging, National Institute of Deafness and other Communication Disorders, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute on Drug Abuse. NHGRI provides the scientific and administrative oversight. The purpose of this acquisition is to provide high quality, high throughput human and mouse genotyping services and statistical genetics expertise dedicated towards finding the genetic basis for disease in support of extramural and intramural research programs supported by the twelve participating Institutes. Services to be provided include: (1) Short tandem repeat (STRP) genotyping to allow whole genome linkage scans of at least 10,000 human samples per year at an average marker spacing of ~10 cM. (2) Single nucleotide polymorphism (SNP) genotyping using 6,000-10,000 uniformly spaced loci to allow SNP whole genome linkage scans of 24,000 human samples per year. (3) SNP genotyping of custom sets of between 380 and 3000 SNPs on 36,000 human DNA samples per year. This genotyping needs to be done in a CLIA-approved manner if required by the investigator?s study design. (4) SNP genotyping of human MHC region with ~1200 or ~2400 SNPs. This genotyping needs to be done in a CLIA-approved manner if required by the investigator?s study design. (5) SNP genotyping of up to ~1500 SNPs in 2,000 mouse DNA samples per year. (6) SNP genotyping at 250,000 to 500,000 loci designed to capture >~80% of the variation in human DNA, when taking human linkage disequilibrium into account, for the purposes of genome-wide association studies. Genotyping for genome wide association studies must have a capacity of 10,000 samples in the first year, increasing to 20,000 samples in years 2-5. (7) Consultation on statistical genetics questions including power estimates for assessing sample size requirements before production genotyping is carried out, and analysis of genotyping data after production genotyping is complete. (8) Strict quality control to include testing of all samples for adequacy of amount and quality of DNA prior to full genotyping. Use of pedigree structure information to test for inheritance errors, misattributed parentage, and incorrect gender assignments, all of which might point to sample mix-ups. Opportunity for investigators who submit their projects to CIDR to replace problematic DNA samples that do not pass pre-testing quality control before production genotyping is undertaken. (9) Accurate quality control reports for each project and an annual summary over all projects on missing data, pedigree structure errors, and blind duplicate error rates, using either available software or designing and implementing novel software to generate these reports. (10) Databases for laboratory information management (tracking samples and reagent usage, DNA and reagent quality control), collecting genotyping results, and analyzing genotypes for data quality control metrics. (11) Ability to provide results on CD-ROM or removable hard disk media in a format mutually agreed upon by the CIDR Program and the submitting Investigator. (12) Data back-up in a secure location off-site that is specially designed to provide protection from physical damage to storage media. (13) Ability to receive and interpret electronically encoded family and pedigree structure information. (14) Capacity to receive >30,000 DNA samples per year from submitting investigators in multi-well, barcode encoded plates. Ability to aliquot, dilute, test, store and genotype these DNA samples without cross-contamination. (15) Expertise in evaluating and implementing novel genotyping technologies and work flow procedures in order to keep CIDR?s methodology up to date and cost effective. (16) Ability to provide SNP genotyping results in a CLIA approved manner upon request for clinical studies. Responses to this synopsis will be evaluated based on the following technical evaluation criteria which are listed in approximate descending order of importance: (1) Evidence of availability and skill of staff, including project management, to provide all of these services including sample and reagent handling, tracking and reagent and sample quality control using a Laboratory Information Management system, high throughput production genotyping, analysis to provide data quality control assessments, statistical genetics expertise in study design and data analysis, and database management. (2) Evidence of ability to hire and retain senior staff with the necessary qualifications to import and/or implement highly technical genotyping methods, work flow procedures, to implement and apply state-of-the-art statistical genetics programs for study design and data analysis, and to import or create novel computer algorithms and programs in support of the goals of the CIDR Program. These qualifications are to include having academic appointments in a university or government-based organized research unit (Department, Branch, Institute or Center) specializing in genetics research. (3) Evidence of prior experience in providing the database support, data back-up, and data analysis required for linkage and association studies involving many thousands of samples and hundreds of thousands of loci. (4) Demonstrated prior experience in high throughput genotyping of DNA samples at a rate of >24,000 samples per year. (5) Demonstrated ability to provide SNP genotyping service on at least two different platforms, with SNP sets ranging in size from a few hundred SNPs to >~250,000 SNPs genotyped per sample. Ability to provide SNP genotyping results on up to 3,000 SNPs per sample in a CLIA approved manner, when requested by the submitting investigator. (6) Demonstrated ability to perform genome-wide STRP genotyping at ~10 cM interval in a highly multiplexed, cost-efficient manner. Johns Hopkins University has been providing these services under a noncompetitive contract since the CIDR program was created in 1996. The NHLBI, on behalf of NHGRI, intends to negotiate on a non-competitive basis with Johns Hopkins University for a five year contract to continue to provide these services. This synopsis is intended to test the market to determine if our planned non-competitive award to Johns Hopkins University should be done competitively instead; there is no solicitation at this time. Responses are due at the following address not later than December 16, 2005: National Institutes of Health, National Heart, Lung, and Blood Institute, Office of Acquisitions, 6701 Rockledge Drive, Room 6138, Bethesda, MD 20892-7902 (use 20817 for express mail) Attention: Lynn M. Furtaw, Contracting Officer. Authority: 41 U.S.C. 253(c)(1) as set forth in FAR 6.302-1. This is not a request for Proposals. See Numbered Note 22.
SN00924967-W 20051104/051102211753 (fbodaily.com)
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