Identification of rare complete BRCA1 gene deletion using a combination of SNP haplotype analysis, MLPA and array-CGH techniques

Excerpt

Large genomic rearrangements (LGRs) escape detection by PCR based methods such as SSCP and DNA sequencing. Although multiplex-ligation-dependent probe amplification (MLPA), developed for detection of LGRs, is fast and easy to perform [1], still in many laboratories PCR-based techniques remain the first step in mutational screening of patients with hereditary breast and ovarian cancer (HBOC) as LGRs are much less frequent than point/small mutations in some populations [2‐4], making MLPA prior to DNA sequencing only marginally cost-effective. Alternatively, detection of unusual BRCA1 SNP haplotypes in an affected individual may be suggestive of hemizygous regions caused by LGRs [5‐9]. However, this latter approach focused only on the index case would not detect complete gene deletions that do not disturb the usual haplotypes. Herein, we report a way how the SNP haplotype analysis of the BRCA1 gene in members within a HBOC family may lead to identification of a complete gene deletion. …