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Next Generation Mapping a novel approach that enables the detection of unbalanced as well as balanced structural variants
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Edité par CCSD -
International audience. Structural variants (SVs) include large unbalanced (CNVs) and balanced variants (insertions, inversions and translocations). Whereas the detection of unbalanced SVs has been significantly improved by technological breakthrough such as Chromosomal Microarray Analysis (CMA), the detection of balanced SVs still relies on karyotype despite its very low resolution. Massively parallel sequencing enables the detection of some SVs but its use in clinical setting is yet limited by technical and computational challenges, among which the read length. Next Generation Mapping using the Bionano system is a novel non-sequencing based technology. Long high molecular weight DNA fragments are labelled at specific sites and then stretched out into a nano-channel system for fluorescence reading. The labelling pattern is then compared to a reference genome pattern allowing for the identification of SVs without complex bioinformatic analyses. We sought to evaluate the performance of this technology and its ease of use in a routine cytogenetic laboratory. Our study includes 29 patients bearing balanced (11 translocations and 4 inversions) or unbalanced SVs (1 unbalanced translocation, 7 CNVs ranging from 500kb to 4Mb), complex chromosomal rearrangements (n=4), isochromosomes (n=2) and one case of aneuploidy, all previously identified by karyotype or CMA. The results are analysed blindly and then compared to karyotype or CMA results. Preliminary data on four samples show reliable detection of the expected SVs. This approach has the potential to improve the resolution of the pangenome detection of different sorts of SVs, and could hence complement or even replace karyotype and CMA as a unique, simple and comprehensive test. This would have a significant clinical impact for diseases in which balanced SVs are mainly involved, such as reproductive diseases and recurrent miscarriages.
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