Comparative genome hybridization on tiling microarrays to detect aneuploidies in yeast

Chromosomal aberrations resulting in aneuploidies have been implicated in the development of most cancers and numerous other genetic disorders. Aneuploidies are a key feature of genomic instability, so classification of these copy number changes will be important in understanding how rearrangements arise and how ongoing instability is maintained. Traditional methods for detecting copy number changes have relatively poor resolution, making accurate detection of breakpoints impossible. The advent of microarray technology and its advance over the years has improved the ability to detect aneuploidies with greater accuracy. Mammalian comparative genome hybridization on microarrays (array-CGH) has been applied to the study of many carcinomas, identifying common copy number changes in key regions including known oncogenes. However, the large size of mammalian genomes has made it impractical to perform whole genome CGH at high resolution. Yeast has been established as a useful model for studying pathways relevant to oncogenesis, particularly those that maintain the integrity of the genome. Given the smaller size of the yeast genome, oligonucleotide tiling arrays have been developed that allow for nucleotide resolution of the whole genome on a single chip. Here we describe in detail how to use these arrays to detect copy number variations in yeast. This method will be useful in many different studies, but particularly in monitoring and cataloguing the changes resulting from genetic instability.