HIGH THROUGHPUT GENOTYPING FOR LOCATING HUMAN DISEASE GENES

Release Date:  October 25, 2001

NOTICE:  NOT-ES-02-004

RFP:  NIH-HG-02-01

National Institute of Environmental Health Sciences

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 NHGRI 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.

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