Identification of origin of unknown derivative chromosomes by array-based comparative genomic hybridization using pre- and postnatal clinical samples

Microarray-based comparative genomic hybridization (array CGH) is a high-resolution and comprehensive method for detecting both genome-wide and chromosome-specific copy-number imbalance. We have developed an array CGH analysis system (consisting of an array CGH chip plus its exclusive analysis software) for constitutional genetic diagnosis and have evaluated the suitability of our system for molecular diagnosis using pre- and postnatal clinical samples. In a blind study, each of the 264 sample karyotypes identified by array CGH analysis was consistent with that identified by traditional karyotype analysis - with one exception, case (47, XXX) - and we were able to identify origins, such as small supernumerary marker chromosomes, which cannot be determined by conventional cytogenetics. We also acquired very accurate, fast and reliable results using a diminutive amount of clinical samples. Taken together, the array CGH platform developed in this study is a rapid, powerful and sensitive technology for pre- and postnatal diagnosis using a very small amount of clinical sample.