AUTOMATED DETECTION OF CRYPTIC REARRANGEMENTS

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This project will develop automated instrumentation and image analysis techniques to detect cryptic chromosomal rearrangements, which are difficult to detect by conventional cytogenetics. It combines two innovative FISH probes: SubTelomeric and Multiplex , with automated metaphase detection and sophisticated image analysis, for screening patients with idiopathic mental retardation or multiple congenital anomalies. Our approach uses readily available subtelomeric or multiplex DNA probes, followed by automated genetic screening. We will develop an imaging system for the automated identification of chromosomes and use sophisticated image analysis for high resolution detection of submicroscopic rearrangements. The Phase I project will evaluate feasibility for the high resolution imaging system, and evaluate the two FISH techniques for efficiency and precision in cryptic rearrangement detection. If subtelomeric probes prove optimal, Phase II will build and test a prototype clinically. If multiplex FISH proves better, Phase II will incorporate the improved algorithms into our existing system. Phase III will commercialize the instrument. This combination of a high resolution imaging system and the innovative FISH approaches (subtelomeric and multiplex), has the potential to become a primary screening method for the detection of cryptic rearrangements. This approach will revolutionize medical genetics, particularly for idiopathic mental retardation, congenital abnormalities, and some cancers. PROPOSED COMMERCIAL APPLICATION As soon as the techniques are developed and qualified for routine application, they will be incorporated into PSI s PowerGene product line of cytogenetics automation equipment, both in new systems sold and as an upgrade to existing systems already in use in cytogenetics labs. Thus commercialization of the technology developed under this project will occur quickly.