Current techniques for the diagnosis of genetic disease are limited by an inability to detect the majority of mutations and polymorphisms in DNA. DNA molecules that differ by one or a few base pairs can most efficiently be distinguished by denaturing gradient gel electrophoresis due to sequence specific differences in melting properties of DNA. However, base changes can be detected only in domains of the molecule that melt first in these gels.Genetics Institute will improve this technique so that base pair changes can be detected in all domains of a DNA molecule. Researchers will modify DNA probes in ways that will significantly alter the melting behavior of DNA hybrids, so that new regions of the DNA molecule will be included in the first melting domain. In addition, experimental data will be used to generate computer models to predict melting behavior of modified DNA molecules. These computer programs can then be used to design optimal probes for detecting sequence changes in and DNA molecule. This technology should be broad enough for application to any gene of interest and could lead to the commercial development of diagnostic tests for a number of genetic diseases.National Institute of General Medical Sciences (NIGMS)
