Chromosome banding is one of the most widely used techniques in routine cytogenetics (1) and has been invaluable in the search for chromosomal aberrations causally related to, for example, congenital mental retardation and malformation syndromes. Conceptual and technical developments in molecular cytogenetics are now enhancing the resolving power of conventional chromosome analysis techniques from the megabase to the kilobase level. Tools that have mediated these developments include (i) the generation of genome-wide clone resources integrated into the finished human genome sequence, (ii) the development of high-throughput microarray platforms, and (iii) the optimization of comparative genomic hybridization protocols and data analysis systems. Together, these developments have accumulated in a so-called 'molecular karyotyping' technology that allows the sensitive and specific detection of single copy number changes of submicroscopic chromosomal regions throughout the entire human genome.

Array-based comparative genomic hybridization (CGH) builds upon previously well-established CGH procedures (2, 3) using differentially labeled test and reference DNAs to be co-hybridized to cloned genomic fragments with known physical locations, in a microarray format (4, 5). In comparison with conventional CGH, the array format provides a higher resolution, a higher dynamic range, and better possibilities for automation. In addition, it allows for direct linking of copy number alterations to known genomic sequences.

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