AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS

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This project will develop automated instrumentation and image analysis techniques to detect, in interphase FISH, gene duplications or deletions which are difficult to detect by routine cytogenetics. There is a growing list of genetic disorders that result from chromosomal anomalies, related to either duplications or deletions. These include: (1) neuropathies; Charcot- Marie-Tooth Disease (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP), (2) neurological disorders; Pelizaeus-Merzbacher Disease (PMD) and X-Linked Spastic Paraplegia (SPG2), (3) muscular wasting disorders; Duchene (DMD) and Becker Muscular Dystrophy (BMD), (4) contiguous-gene syndromes; Smith-Magenis Syndrome (SMS). Our approach is to use readily available DNA probes, followed by automated genetic screening to detect duplications/deletions. We will develop an imaging system for the automated identification of interphase cells, and use sophisticated image analysis for high-resolution detection and separation of microscopic rearrangements. The Phase I project will evaluate feasibility of the automated imaging system, and evaluate the efficiency and precision of FISH dot identification and separation. Phase II will build and test a prototype clinically. Phase III will commercialize the instrument. This high resolution imaging system, incorporating innovative FISH dot detection algorithms,has tremendous potential to become a primary screening method for detecting gene duplications/deletions. Computer automation will make genetic screening practical on a large scale by reducing costs and relieving humans of tedious duties. This approach will be most valuable to medical genetics, particularly for screening CMT1A/HNPP, PMD/SPG2, DMD/BMD, SMS. PROPOSED COMMERCIAL APPLICATIONS: 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.