Comparative genome hybridization reveals widespread aneuploidy inCandida albicanslaboratory strains.

Clinical strains ofCandida albicansare highly tolerant of aneuploidies and other genome rearrangements. We have used comparative genome hybridization (CGH), in an array format, to analyse the copy number of over 6000 open reading frames (ORFs) in the genomic DNA ofC. albicanslaboratory strains carrying one (CAI-4) to three (BWP17) auxotrophies. We find that during disruption of theHIS1locus all genes telomeric toHIS1were deleted and telomeric repeats were added to a 9 nt sequence within the transforming DNA. This deletion occurred in∼10% of transformants analysed and was stably maintained through two additional rounds of transformation and counterselection of the transformation marker. In one example, the deletion was repaired, apparently via break-induced replication. Furthermore, all CAI-4 strains tested were trisomic for chromosome 2 although this trisomy appears to be unstable, as it is not detected in strains subsequently derived from CAI-4. Our data indicate CGH arrays can be used to detect monosomies and trisomies, to predict the sites of chromosome breaks, and to identify chromosomal aberrations that have not been detected with other approaches inC. albicansstrains. Furthermore, they highlight the high level of genome instability inC. albicanslaboratory strains exposed to the stress of transformation and counterselection on 5-fluoro-orotic acid. [ABSTRACT FROM AUTHOR]