HIGH THROUGHPUT GENOTYPING FOR LOCATING HUMAN DISEASE GENES

Release Date:  November 26, 2001

NOTICE:  NOT-ES-02-005

RFP AVAILABLE:  NIH-ES-02-01

National Institute of Environmental Health Sciences

Correction:  This action originally publicized in the CBD dated October 
23, 2001, is revised to correctly state the RFP No. as NIH-ES-02-01 
(not NIH-HG-02-01) and to correctly state the number of DNA samples to 
be obtained over 5 years and to correctly state the number of DNA 
samples obtained each performance year.  All the corrections are made 
in uppercase letters.  The revised synopsis of the requirement is 
as follows:

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 IDRB/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 to the 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 genotyping 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 (LABELED TUBES 
CONTAINING DNA WILL BE PROVIDED TO THE CONTRACTOR BY INVESTIGATORS WHO 
HAVE BEEN APPROVED FOR GENOTYPING SERVICES AT CIDR.),quantify the 
amount of DNA and aliquot the DNA into several equivalent labeled 
samples at concentrations to be specified by the Project Officer 
(APPROXIMATELY 105,000 DNA SAMPLES WILL BE OBTAINED OVER 5 YEARS 
(ANTICIPATED YEARLY NUMBER IS 17,000 IN YEAR 1, 22,000 IN YEARS 2 
THROUGH 5), OF THESE, UP TO 10,500 WILL BE OF MURINE ORIGIN (1,700 IN 
FIRST YEAR, 22,000 IN YEARS 2 THROUGH 5),ensure that adequate caution 
is maintained by employees working with materials that present 
biological hazard, e.g., human tissues, develop an inventory system for 
tracking and storage of blood, DNA samples synthetic DNA primers used 
in GENOTYPING ,and OTHER REAGENTS USED IN DNA SEQUENCING AND polymerase 
chain reaction protocols, ENSURE STORAGE OF INVENTORY AND QUALITY 
CONTROL INFORMATION ABOUT DNA IN THE DATABASE SHALL INCLUDE, BUT IS NOT 
LIMITED TO, THE FOLLOWING INFORMATION: SUBJECT ID NUMBERS, NUMBER OF 
LABELED VIALS 260/280 ABSORPTION READINGS AND RATIOS, ETC., ENSURE 
STORAGE OF OLIGONUCLEOTIDES WHICH SHALL INCLUDE, BUT IS NOT LIMITED TO 
,PRIMER SET ID NUMBERS, NUMBER OF LABELED VIALS, OLIGONUCLEOTIDES 
SYNTHESIS QUALITY CONTROL DATA FROM MANUFACTURER, ETC.,  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 17,000 DNA samples IN YEAR ONE AND 22,000 DNA 
SAMPLES (IN EACH OF YEARS 2-5) THAT ARE 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, 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 WHEN SAMPLES ARE FROM PEDIGREES LARGE ENOUGH TO 
WARRANT SUCH ANALYSIS, 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% FOR HUMAN SAMPLES AND 10% FOR MOUSE SAMPLES. (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, ANOVA, 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.  (10) ESTABLISH AND STAFF A RESEARCH & DEVELOPMENT 
UNIT TO DESIGN, DEVELOP AND TEST ASSAYS FOR DETECTING SINGLE NUCLEOTIDE 
POLYMORPHISMS (SNPs) IN HUMAN DNA. PROJECT OFFICER SHALL SPECIFY WHICH 
GENOTYPING METHOD WILL BE USED AND WHICH SNP ASSAYS WILL BE DEVELOPED.  
GOAL IS TO HAVE NO FEWER THAN 2000 WORKING ASSAYS FOR SNPs THROUGHOUT 
THE HUMAN GENOME DISTRIBUTED AS SPECIFIED BY PROJECT OFFICER BY THE END 
OF YEAR ONE.  AT THE OPTION OF THE PROJECT OFFICER ADDITIONAL SNP  
ASSAYS MAY NEED TO BE DESIGNED, DEVELOPED, AND TESTED AT A RATE OF UP 
TO 5,000 SNP ASSAYS PER YEAR FOR YEARS 2 THROUGH 5. (11) MODIFY AND 
REFINE, AS NEEDED, THE SET OF MOUSE MICROSATELLITE MARKERS TO MAKE SURE 
THAT MARKERS THAT SHOW A FAILURE RATE >10% ARE REPLACED BY OTHER, 
NEARBY MARKERS, WITH A HIGHER SUCCESS RATE (>90%).  GENOTYPE UP TO AN 
ADDITIONAL 24 STRAINS OF MICE (UP TO 8 PER YEAR FOR EARS 1 -3) AT ALL 
MARKERS IN THE MOUSE PANEL, AS SPECIFIED BY THE PROJECT OFFICER. It is 
anticipated that approximately 11 million genotypes shall be performed 
annually.  The Government anticipates that this work will take 
approximately 724,000 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 15, 2001.  See Numbered Notes 22 and 26.

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