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FBO DAILY ISSUE OF AUGUST 24, 2011 FBO #3560
SOLICITATION NOTICE

B -- Whole Exome Sequencing of Genes Underlying Subclinical Atherosclerosis

Notice Date

8/22/2011
 

Notice Type

Presolicitation
 

NAICS

541712 — Research and Development in the Physical, Engineering, and Life Sciences (except Biotechnology)
 

Contracting Office

Department of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute, Rockledge Dr. Bethesda, MD, Office of Acquisitions, 6701 Rockledge Dr RKL2/6100 MSC 7902, Bethesda, Maryland, 20892-7902
 

ZIP Code

20892-7902
 

Solicitation Number

NHLBI-CSB-(HL)-2011-283-DDC
 

Archive Date

9/9/2011
 

Point of Contact

Deborah - Coulter, Phone: (301) 435-0368
 

E-Mail Address

dc143b@nih.gov
(dc143b@nih.gov)
 

Small Business Set-Aside

N/A
 

Description

THIS IS A NOTICE OF INTENT, NOT A REQUEST FOR A PROPOSAL. A SOLICITATION DOCUMENT WILL NOT BE ISSUED AND PROPOSALS WILL NOT BE REQUESTED. The COAC Services Branch, Office of Acquisitions, DERA, National Heart, Lung, and Blood Institute (NHLBI), NIH, for the Framingham Heart Study/Center for Cardiovascular Genomics (FHS)/(CCG), intends to negotiate and award a purchase order on a noncompetitive sole source basis to Broad Institute, Seven Cambridge Center, Cambridge, MA 02142, for the Whole Exome Sequencing of Genes Underlying Subclinical Atherosclerosis services as outline below. The reference number: NHLBI-CSB-(HL)-2011-283-DDC Background Cardiovascular disease (CVD) is the leading cause of death and serious illness in the United States. In 1948, the Framingham Heart Study (FHS) -- under the direction of the National Heart Institute (now known as the National Heart, Lung, and Blood Institute; NHLBI) -- embarked on an ambitious project in health research. At the time, little was known about the general causes of heart disease and stroke, but the death rates for CVD had been increasing steadily since the beginning of the century and had become an American epidemic. Purpose and Objectives: The objective of the FHS has been to identify the common factors or characteristics that contribute to CVD by following its development over time in a large group of participants who had not yet developed overt symptoms of CVD or suffered a heart attack or stroke. The FHS continues to make important scientific contributions by enhancing its research capabilities and capitalizing on its inherent resources. New diagnostic technologies, such as carotid-artery ultrasound to measure as carotid intimal medial thickness (IMT) and plaque, multidetector computerized tomography of the coronary arteries to measure coronary artery calcium (CAC) and aortic calcium (AC) have been completed in two serial examination cycles of the FHS. While pursuing the study's established research goals, the NHLBI and the Framingham investigators have expanded their research into other areas such as the role of genetic factors in CVD. Framingham investigators also collaborate with leading researchers from around the country and throughout the world on genetics and genomics projects in subclinical atherosclerosis, myocardial infarction, stroke and dementia, as well as risk factors for these conditions, including hypertension, hyperlipidemia and diabetes. In the largest genomewide association studies (GWAS) for subclinical atherosclerosis to date, our group has described for the first time common genetic variants (single nucleotide polymorphisms, or SNPs) in multiple genes underlying carotid IMT/plaque and CAC. Several of these SNPs are concordant with loci underlying myocardial infarction and lipids. We hypothesize that a substantial proportion of the unknown heritability of clinical CVD and subclinical atherosclerosis and its risk factors is determined by low frequency and rare ("private") genetic variants. Sequencing of the entire exome (exomewide sequencing) using next-generation DNA sequencing methodology is now underway to discover causal variants underlying clinically apparent CVD and CVD risk factors in research participants at the extremes of these conditions; further, exomewide studies are underway in families with rare, highly penetrate conditions. However, no exomewide studies are yet planned to discover the role of lower frequency variants in subclinical atherosclerosis or in collections of multiple families. This project seeks to identify the low frequency and rare genetic sequence variations underlying subclinical atherosclerosis in families drawn from the FHS. The presence and quantity of subclinical atherosclerosis has been determined by carotid ultrasonography (as IMT and plaque) in the Offspring cohort, and by computed tomography testing (as CAC and AC) in the Offspring and Gen3 cohorts. Increasing levels of carotid IMT/plaque and CAC each independently predict the incidence of myocardial infarction and stroke, leading causes of death and morbidity in men and women. We propose to conduct exomewide sequencing in individuals from multiple families harboring participants with evidence of high levels of subclinical atherosclerosis. Exome sequence data from the Broad Institute, as well as GWAS data, are available for secondary analyses in dbGaP to Dr. O'Donnell through approved research proposals for up to 1000 FHS participants as well as several thousand additional participants from other NHLBI cohorts. The Broad resequencing facility will conduct sequencing of DNA in at least 200 individuals and up to 300 total individuals. Sequencing will be performed using 1 mcg of DNA, which provides enough material for validation genotyping and repeat analysis of any failed samples. Sequencing will be conducted using next-generation sequencing protocols that have been refined in other large exome sequencing projects (Illumina paired-end resequencing). The period of performance for this contract is September 30, 2011 through September 29 2012. I. Contractor Requirements A. Contractor will provide whole exome sequence variant information (VCF files) on at least 200 individuals but up to 300 total individuals. B. Contractor will provide sequencing services to sequence the entire exome in up to 300 but at least 200 DNA samples. C. The Contractor will provide high quality sequencing results with a. a call rate in excess of 80% b. reproducibility in excess of 99% D. The contractor will accept for genotyping SNPs for which Reference Sequence (RefSeq) accession numbers (rs numbers) are available as well as SNPs for which no accession number is available, but for which flanking sequence is provided. In such cases NHLBI will provide the flanking sequence information in FASTA format. The Contractor will review the requested assays and return SNP Score files to NHLBI. E. Quality control measures will be applied by the Contractor and genotyping results from each genotype plate will be accompanied by quality control information reflecting call rate, reproducibility rate, and other appropriate measures of quality. F. Contractor will specify any special packaging, marking, or shipping instructions for plates to be shipped for genotyping. G. Each DNA sample received will be identified by the Contractor using the identifiers provided by NHLBI. II. Government Responsibilities A. Using blinded replicates and family structure data, NHLBI will inspect the results provided by the Contractor and review them for fulfillment of the quality control measures stipulated above (Section IA). SNPs that do not fulfill quality metrics will be identified by NHLBI (Dr. Hwang at the NHLBI Framingham Heart Study). The Contractor will be notified about genotyping quality failure within 30 days of receipt by NHLBI of the final genotyping results files. NHLBI will be credited for any SNPs that do not meet specified quality measures. B. NHLBI will provide to the Contractor plates with standard concentrations of DNA and identifiers for each plate. In addition, NHLBI will provide a list of identifiers for each DNA sample within each plate. III. Reporting Requirements and Deliverables A. Genotyping results as VCF files will be returned by Contractor to NHLBI in a standard VCF format in a nonproprietary database in which each SNP is identified by standard accession number or by FASTA number when an accession number is not available. B. Return of genotyping by the Contractor will be accompanied by summary quality control measures for each DNA plate and for the project overall. C. Genotyping will be returned to NHLBI within 12-16 weeks of receipt of DNA samples from NHLBI. D. Contractor will maintain the DNA plates in the event additional genotyping is required. Program Management and Control Requirements No special management or control systems are required under this contract.
 

Web Link

FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NHLBI/NHLBI-CSB-(HL)-2011-283-DDC/listing.html)
 

Place of Performance

Address: NIh, Framingham, Massachusetts, 01702, United States

Zip Code: 01702
 

Record

SN02544491-W 20110824/110822235645-f3311803c2b3ef34e858eaccace60c03 (fbodaily.com)
 

Source

FedBizOpps Link to This Notice
(may not be valid after Archive Date)

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