Our goal is the development of a high-throughput automated sequencing instrument adapted for identification of rarely present mutations and polymorphism in mixed populations of DNA molecules and validation of the instrument using the p53 gene as a model system. Operation of the machine is based on a novel detection technique which offers the ultra-high resolution of mixed fluorescent markers. Main features of the machine: . analysis of mixed DNA samples with 1% resolution; . throughput of 6,000,000 bp/year; . low amount of labeled DNA material; . Easy-to-replace capillary cassette; . adapted to color sequencing with different dye sets; In Phase 1 we shall demonstrate a feasibility of 1% resolution of mixed DNA samples and test this detection system using clinical DNA material. In Phase II we shall develop a pilot prototype of the machine and validate the machines using the p53 gene as a model system. In Phase III we shall organize manufacturing of the 12-capillary cassettes and 12-lane automated sequence for diagnostics of mixed DNA samples.
The proposed automated sequencing machine will find applications in clinical diagnostics of genetic disease, primarily cancer. Its unique capability to precisely quantify contaminated DNA samples will ensure a dominant position in an important market segment.