Prenatal Blood Group Analysis in High Risk Pregnancies
Small Business Information
30 Spring Mill Drive, Malvern, PA, 19355
AbstractThis is to develop an assay for the identification of fetal blood group antigens using a DNA basedassay method that would allow the use of cells obtained at amniocentesis. The Investigator indicatesapproximately 16% of all multigravida pregnancies in the United States occur in women who are Rhnegative and 84% of the male population is Rh positive, approximately 13% of fetuses are at risk fordevelopment of a hemolytic diseases in the newborn due to Rh incompatibility. Although less than onepercent of fetuses actually develop full blown erythroblastosis fetalis, this outcome is so severe thatserial amniocentesis and percutaneous umbilical blood sampling was adopted for use in all multigravidaRh pregnancies by the American College of Obstetricians and Gynecologists. This is required becauseall women at risk, even though approximately 16% of the total women at risk are bearing Rh negativefetuses and thus are at no risk for hemolytic disease of the newborn. In order to achieve the goals ofdesired, the Investigator plans to develop a commercial diagnostic test. His Specific Aims inaccomplishing this goal are (1) to use PCR and DNA sequencing for molecular characterization of multipleRh forms obtained from clinical partners, (2) correlate the DNA sequence information with serologicaldata, (3) development of a DNA heteroduplex screen that will allow rapid identification of multiplealleles,and (4) screening, identification and clinical correlation of Rh isoforms from amniocenteses todemonstrate the utility of the test in predicting hemolytic disease in the newborn. Thus, during PhaseI of this proposal, the Investigator plans to identify the major Rh isoforms and by demonstrating thatDNA based technology can be adapted to amniotic specimens. Subsequently during Phase II, he plansto convert to laboratory procedures for Rh isoforms into a kit format that can be used by any laboratoryperforming PCR amplifications of DNA samples. He recognizes that the specific type of assay procedurefor identifying isoforms will be governed to some extent by the number of alleles that are identifiedduring phase I. If the allele number is large, heteroduplex method will be employed and converted toamplified kit formats for direct analysis on amniotic samples. He indicates that his laboratory hasdemonstrated that mutant alleles from a variety of genetic disorders can be identified in this manner andhas a patent pending on the method of using heteroduplex patterns for identification of specific alleles.He plans to include all the components in kits needed for performance of the tests. This will includesmall precast gels, all necessary primers, buffers, a inexpensive gel apparatus and a visual allele patternrecognition template. If there is a low number of alleles, they plan to adopt an allele specific oligonu-cleotide assay based on a microtiter plate format. This would incorporate fluorescently labeled probes,along with a commercially available microtiter plate reader.
* information listed above is at the time of submission.