MAPPING SEGMENTAL IMBALANCES USING COMPARATIVE GENOMIC HYBRIDIZATION AND EIGENANALYSIS

We have tested a new approach to comparative genomic hybridization (CG H) analysis using digital ratio images and eigenanalysis, which allows the recognition of consistent patterns along the chromosomes and disc ards random (background noise) patterns. We have performed test experi ments using genomic DNAs from a patient with a duplication, another wi th a deletion of a chromosome segment, and a prostate cancer biopsy. I mage ratio analysis was performed, and ratio images of the relevant ch romosome were subjected to eigenanalysis. The results showed a high-co ntrast enhancement of the regions corresponding to the unbalanced geno mic segment, with clearly defined limits between normal and abnormal f luorescence ratios. The combination of digital ratio images and eigena nalysis allowed the precise mapping of unbalanced regions consistent w ith other methods of analysis. Because there is no limit to the number of chromosomes that can be analyzed at any one time, the method has t he potential of increasing the sensitivity of CGH by reducing the nois e component.