A -- HIGH THROUGHPUT GENOTYPING FOR LOCATING HUMAN DISEASE GENES!!

Notice Date

October 23, 2001

Contracting Office

National Institutes of Environmental Health Sciences, Research Contracts Branch, DERT, P.O. Box 12874, Building 4401, Research Commons, 79 T.W. Alexander Drive, Research Triangle Park, NC 27709

ZIP Code

27709

Solicitation Number

NIH-HG-02-01

Response Due

December 8, 2001

Point of Contact

Contact Velvet M. Torain, Contract Specialist, 919-541-0400/Phillip D. Jones, Contracting Officer,919-541-0426,Fax No. 919-541-2712!!

Description

The Government intends to negotiate a contract with Johns Hopkins University, School of Medicine, to operate the Center for Inherited Disease Research (CIDR), a unit within the National Human Genome Research Institute (NHGRI), located at Johns Hopkins Bayview Research Campus, Triad Technology Center, Baltimore Maryland. This acquisition is for service support of the NHGRI's efforts in mapping genes responsible for "complex" inheritance diseases. Johns Hopkins shall perform high throughput genotyping for locating human disease genes. Specifically Johns Hopkins University shall be required to (1)implement and support relational databases, in ORACLE , or other database platforms as specified by the Project Officer, for storage and retrieval of clinical, genotypic, laboratory, and phenotypic data, by furnishing the following "representative" type of services such as computerized database for laboratory information collectively described as a laboratory information management system, computerized database for genotyping data, both finished and raw for experimental samples and control samples as well as bland samples, computerized database for clinical and epidemiological("phenotypic") data when necessary according to the requirements of a particular project, provide usual computer equipment and supplies (shall be UNIX compatible). The databases shall employ electronic worksheets into which laboratory workers will enter data on line using bar-code readers.(2)Establish and maintain local area computer network connectivity to allow input of data into the database from all computer workstations in the Government and CIDR offices and laboratories from both contractor and Government personnel. (3) Establish and maintain computer network connectivity from all computers within the local area network at CIDR and NGHRI and to the internet by a minimum of the equivalent of T3 line. (4) Assist in the storage of clinical and epidemiological data in the electronic database as specified by the Project Officer. To provide the following "representative" types of services such as, hold the code for samples in a secure file so that the database itself contains no identifiers that could be used to trace the samples or data back to particular individuals; enter computer readable data into the database; insure clinical and phenotypic data are carefully entered and cross-referenced to any DNA samples and genotype data generated from the sample; verify that data entry for an individual sample is accurate by independent recording; identify types, numbers, and qualifications of personnel necessary for task completion. (5) Assist in the collection, processing and storage of biological specimens from individuals participating in research studies by furnishing the following types of "representative" services such as design, develop, and furnish Project Officer written procedural manuals for collecting, transporting, and storing biological specimens, for extracting DNA, for hydrating, diluting and storing synthetic olilgonucleotides and other reagents used in fluorescence-tagged genoytping and polymerase chain reaction procedures; obtain necessary permission and approvals for collecting of biological materials required for laboratory studies; furnish all equipment necessary to carry out extraction of high molecular weight DNA, perform quality control measurements, and store DNA and other biological specimens at 4, -20 or -70 decrees C as specified by the Project Officer; extract DNA from each tube as requested, quantify the amount of DNA, and aliquot the DNA into several equivalent labeled samples at concentrations to be specified by the Project Officer; ensure that adequate caution is maintained by employees working with materials that present a biological hazard, e.g. human tissues; develop an inventory system for tracking and storage of blood, DNA samples synthetic DNA primers used in DNA sequencing and polymerase chain reaction protocols; employ electronic worksheets into which Government researchers can enter sample identification and quality control data from biological samples, DNA, and oligonucleotides, and other reagents on line either using the keyboard or bar-code readers; at the end of a study return all inventoried DNA and other biological samples to the appropriate investigators; identify types, numbers, and qualifications of personnel necessary for task completion. (6) Implement and apply methods for rapid genotyping of 12,000 DNA samples prepared and collected from researchers whose applications to use CIDR have been approved by the Board. "Representative" type services shall be provided such as employ methods for genotyping large numbers of individuals using but not limited to, gel-based resolution of micro-satellite marker alleles generated by PCR, separated on automated sequencing gels, and detected by fluorescence of dyes attached to micro satellite primers shall be used; ensure all genotypic data obtained from each individual sample includes, but is not limited to, sample ID number, the marker at which genotype is being determined, and results of genotyping expressed as allele sizes, such quality control variables such as reagent concentrations, reagent lots used, polymerase chain reaction parameters, PCR machine used, data of genotyping and researcher carrying out the genotyping; obtain genotype information for each sample and record data into the database directly using software that "reads" the genotype output from the automated sequencer for each sample; develop or import software required to read genotype information to allow the direct reading of genotype data into the database; apply all necessary statistical analyses to monitor genotyping data to insure accuracy, reproducibility, consistency with Mendelian Inheritance and Hardy-Weinberg equilibrium; identify types, numbers, and qualifications of personnel necessary for task completion; by means of blind duplicates, produce genotype data for which the error rate as determined using blind duplicates is less than 1%. The inconsistency rate as determined from Mendelian analysis must be less than 0.4%, and missing data less than 5%. (7)Assist in the implementation and application of computer-based statistical methods to locate genes responsible for complex heritable traits in humans. "Representative" types of services such as develop or import from elsewhere statistical methods for analyzing clinical and epidemiological data and the co-inheritance of DNA markers and various complex traits such as, but not limited to, multi variate regression, logistic regression, life table procedures, ANO VA , linkage analysis of discrete traits, quantitative trait linkage mapping, affected pedigree member methods, sibpair methods, identify by state and descent methods, transmission disequilibrium testing, association methods, and other methods developed by the statistical genetics community; implement statistical methods into usable computer programs either by importing them from elsewhere or by designing and constructing them; test for power, robustness, and sensitivity by simulation studies and analysis of actual data sets in order to assess their applicability to a variety of complex hereditary diseases; apply statistical methods to identify regions of the human genome that contribute to the hereditary basis of human disease. (8) At the end of each study, supply each CIDR user with paper and electronic copies (on CD-ROM or other appropriate media) of genotype data formatted into tables that can be read and used by standard statistical genetics and linkage analysis software packages. (9) Document all the individual steps in a specific study, and establish and maintain orderly records of all relevant material so that any aspect of a study can be retrieved by Government staff at any point during its course. It is anticipated that approximately 11 million genotypes shall be performed annually. The Government anticipates that this work will take approximately 8,855 direct labor hours over five years. The contract period of performance will be for five years, with an anticipated award date of March 1, 2002. Authority: 41USC253(c)(1), as set forth in FAR 6.302-1 -- Only One Responsible Source. The existing contract for this work is contract number N01-HG-65403, with Johns Hopkins University, School of Medicine. Any other interested sources desiring consideration for this requirement must fully identify their interest and capabilities to the Contract Specialist/Contracting Officer listed above by no later than December 7, 2001. See Numbered Notes 22 and 26*****

Record

Loren Data Corp. 20011025/ASOL003.HTM (W-296 SN5113O5)