 Hi, today I would like to present you a study published in Human Mutation that describes novel genetic tests for the detection of large enrichment in the breast cancer genes BRCA-1 and BRCA-2. The study has been mainly carried out in the research and development laboratories of Genomic Vision. Genomic Vision is a biotechnology company based in Paris, specialized in the development of genetic tests and a search tool for life science. The company has been founded in 2005 by Dr. Aaron Ben-Simon as a spin-off of the Panster Institute. We collaborated closely with Etienne Roulot and colleagues from the Hôpital Réunion in Saint-Claude, which is part of the Institut Curie. As you may know, breast cancer affects 10% of the female population. It is estimated that 1.4 million women will be diagnosed of breast cancer annually. Almost half a million women are dying of breast cancer worldwide. General mutations in the breast cancer genes BRCA-1 and BRCA-2 account for 5-10% of all breast cancer cases. A mutation in one of these two genes confers 10-20 times higher risk to develop breast cancer. Most common mutations have a small size and are mostly point mutations. These small mutations can be easily detected by sequencing. Mutations also include large rearrangements, mostly deletions and duplications of large genomic regions that escape detection by sequencing. It is becoming evident that even sophisticated technology like next generation sequencing show big limitation in the detection of these large rearrangements. The reason is the high content of repetitive sequences, about 50% in both genes. As you can see, hollow sequences represent 42% of the BRCA-1 genomic region and 70% of BRCA-2. The bottom line is that there is a clear need for alternative technologies capable of detecting large rearrangements efficiently. We propose molecular combing as a technology for the detection and characterizations of large rearrangements and other structural variations. What is molecular combing? It is a powerful fish-based technique for direct visualization of single DNA molecules that are stretched and attached to specially treated glass surfaces. The slides are lifted out of the solution and DNA is combed by the action of the receding meniscus. DNA is uniformly stretched and irreversibly bound to the surface. After combing, the slide is covered with the line double-stranded DNA molecules and up to 200 genomes can be visualized in parallel. Fluorescent DNA probes bind specifically to comb DNA and the generated signals can be analyzed by automated fluorescence microscopy. Molecular combing is particularly suited for the detection of deletions, amplifications, inversions and copy number variations. Structural variations in the genome can be detected thanks to genomic Morse codes. A genomic Morse code is a series of signals and gaps designed to physically map and define with a specific signature a particular genomic region. We have designed high-resolution genomic Morse codes to physically map the BRCA-1 and BRCA-2 genomic regions. Each exon is associated to a specific signal or gap so that a large rearrangement can be precisely mapped on the gene but also on the genomic regions surrounding the gene. We detected and characterized 10 different large rearrangements with sizes of 3 to 40 kilobases. We characterized deletions and duplications on both genes, including four novel mutations. The mutations were confirmed by high-resolution CGH rays and breakpoints were characterized by sequencing. Molecular combing allowed to localize and visualize several tandem repeat duplications on both genes. This is really a big added value of our test. In fact, CGH rays cannot be applied to fully characterize tandem duplications. As a conclusion, we propose molecular combing as a diagnostic genetic test for the detection and characterizations of large rearrangements in the genes BRCA-1 and BRCA-2. Our test can be combined with an essay capable of detecting point mutations. If you want to know more about this exciting study, we invite you to read the manuscript in the current issue of human mutation. Thank you for your attention and happy reading!