Using QuantiSNP on the combined datasets (∼400,000 SNPs) all breakpoints were mapped with high-resolution (Supplementary Table S2A). In Figure 6, we compare the performance of BeadStudio LOH+ and QuantiSNP in mapping the breakpoint using the HumanHap300 data to the data collected with other technologies (FISH, sequencing, PCR and MLPA). QuantiSNP accurately mapped 12/15 breakpoints analysed, while BeadStudio LOH+ mapping was accurate only in 6 instances. Some of the deletion/duplication events were detected and mapped in multiple segments. While this never happened (0/11) for QuantiSNP, BeadStudio LOH+ broke the deletion/duplication events in 3/11 cases analysed. Using QuantiSNP on sample No.14 (previously characterized by exon-specific PCR to harbour deletion of exons 46–50 of the DMD gene), we were able to design primers for an amplicon of predicted maximum size 7428 bp. The long-range PCR resulted in a 4627 bp fragment, that was subsequently analysed by restriction enzyme mapping allowing the sequencing across the breakpoint of a smaller PCR amplicon (Figure 7). BeadStudio LOH+ did not detect the deletion on chromosome 3p in sample No.18, while this was detected, and correctly mapped, in the combined dataset QuantiSNP analysis.
