The development and validation of novel approaches to accurately and quickly map copy number changes in the human genome is important for the implementation of novel diagnostic strategies. Oligonucleotide array platforms originally developed for SNP genotyping have been successfully used for segmental aneuploidy profiling (4,5,7). Here we present a novel statistical algorithm that uses Objective Bayes inference for a HMM with calibrated prior parameter settings. We validated the technique using Illumina BeadArray™ SNP genotyping technology on well-characterized clinical samples. OB-HMMs resulted in the confident identification with high probability of known copy number alterations, as verified with other molecular cytogenetics and/or molecular biology techniques. Our results show the power of the QuantiSNP approach in accurately mapping breakpoints (12/15 versus only 6 for BeadStudio) (Figure 6) and demonstrate an instance where only the QuantiSNP mapping allowed the direct sequencing and subsequent definition of the breakpoint at the base-pair level (sample No.14) (Figure 7). As for the minimum size in base pairs of copy number changes that can be identified, this is limited only by the resolution and coverage of the SNPs on
