AUTOMATED DETECTION OF CRYPTIC REARRANGEMENTS

该项目将开发自动化仪器和图像分析技术，以检测传统细胞遗传学难以检测的隐性染色体重排。 它结合了两种创新的FISH探针：SubTelomeric和Multiplex，具有自动化中期检测和复杂的图像分析，用于筛查特发性精神发育迟滞或多种先天性异常的患者。我们的方法使用容易获得的亚端粒或多重DNA探针，然后进行自动遗传筛选。 我们将开发一种用于染色体自动识别的成像系统，并使用复杂的图像分析来进行亚显微重排的高分辨率检测。第一阶段项目将评估高分辨率成像系统的可行性，并评估两种FISH技术在检测隐性重排方面的效率和精度。如果亚端粒探针被证明是最佳的，第二阶段将建立和临床测试原型。 如果多重FISH证明更好，第二阶段将把改进的算法纳入我们现有的系统。 第三阶段将使该仪器商业化。这种高分辨率成像系统和创新的FISH方法（亚端粒和多重）的组合，有可能成为一个主要的筛选方法检测隐蔽重排。 这种方法将彻底改变医学遗传学，特别是对特发性智力低下，先天性异常和某些癌症。一旦这些技术被开发出来并获得常规应用的资格，它们将被纳入PSI的细胞遗传学自动化设备PowerGene产品线，无论是在新的系统中销售，还是作为对细胞遗传学实验室已经使用的现有系统的升级。 因此，在该项目下开发的技术将很快实现商业化。

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.