AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS

该项目将开发自动化仪器和图像分析技术，以检测间期FISH中常规细胞遗传学难以检测的基因复制或缺失。越来越多的遗传疾病是由染色体异常引起的，这些异常与重复或缺失有关。这些包括：(1)神经病变；Charcot- Marie-Tooth病（CMT1A）和遗传性神经病伴压迫性麻痹（HNPP），(2)神经系统疾病；Pelizaeus-Merzbacher病（PMD）和x连锁痉挛性截瘫（SPG2），(3)肌肉萎缩疾病；Duchene （DMD）和Becker Muscular Dystrophy (BMD),(4)邻接基因综合征；Smith-Magenis综合征（SMS）。我们的方法是使用现成的DNA探针，然后通过自动遗传筛选来检测重复/缺失。我们将开发一种成像系统，用于间期细胞的自动识别，并使用复杂的图像分析对微观重排进行高分辨率检测和分离。一期项目将评估自动化成像系统的可行性，并评估FISH点识别和分离的效率和精度。第二阶段将建立和临床测试原型。第三阶段将使该仪器商业化。这种高分辨率成像系统，结合了创新的FISH点检测算法，具有巨大的潜力，成为检测基因重复/缺失的主要筛选方法。计算机自动化将通过降低成本和减轻人类繁琐的工作，使基因筛查在大规模上变得可行。该方法将对医学遗传学最有价值，特别是筛选CMT1A/HNPP， PMD/SPG2, DMD/BMD， SMS。建议的商业应用：一旦这些技术被开发出来并符合常规应用条件，它们将被纳入PSI的PowerGene细胞遗传学自动化设备产品线，无论是在新销售的系统中，还是在细胞遗传学实验室中已经使用的现有系统的升级。因此，在这个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, 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.