TY - JOUR T1 - Next generation cytogenetics: genome-imaging enables comprehensive structural variant detection for 100 constitutional chromosomal aberrations in 85 samples JF - bioRxiv DO - 10.1101/2020.07.15.205245 SP - 2020.07.15.205245 AU - Tuomo Mantere AU - Kornelia Neveling AU - Céline Pebrel-Richard AU - Marion Benoist AU - Guillaume van der Zande AU - Ellen Kater-Baats AU - Imane Baatout AU - Ronald van Beek AU - Tony Yammine AU - Michiel Oorsprong AU - Daniel Olde-Weghuis AU - Wed Majdali AU - Susan Vermeulen AU - Marc Pauper AU - Aziza Lebbar AU - Marian Stevens-Kroef AU - Damien Sanlaville AU - Dominique Smeets AU - Jean Michel Dupont AU - Alexander Hoischen AU - Caroline Schluth-Bolard AU - Laïla El Khattabi Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/16/2020.07.15.205245.abstract N2 - Chromosomal aberrations and structural variations are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics, karyotyping and CNV-microarrays, in spite of the low resolution of the first one and the inability to detect neither balanced SVs nor to provide the genomic localization or the orientation of duplicated segments, of the latter. We here investigated the clinical utility of high resolution optical mapping by genome imaging for patients carrying known chromosomal aberrations in a context of constitutional conditions.For 85 samples, ultra-high molecular weight gDNA was isolated either from blood or cultured cells. After labeling, DNA was processed and imaged on the Saphyr instrument (Bionano Genomics). A de novo genome assembly was performed followed by SV and CNV calling and annotation. Results were compared to known aberrations from standard-of-care tests (karyotype, FISH and/or CNV-microarray).In total, we analyzed 100 chromosomal aberrations including 7 aneuploidies, 35 translocations, 6 inversions, 2 insertions, 39 copy number variations (20 deletions and 19 duplications), 6 isochromosomes, 1 ring chromosome and 4 complex rearrangements. High resolution optical mapping reached 100% concordance compared to standard assays for all aberrations with non-centromeric breakpoints.Our study demonstrates the ability of high resolution optical mapping to detect almost all types of chromosomal aberrations within the spectrum of karyotype, FISH and CNV-microarray. These results highlight its potential to replace these techniques, and provide a cost-effective and easy-to-use technique that would allow for comprehensive detection of chromosomal aberrations.Competing Interest StatementDeclaration of Interests Bionano Genomics sponsored part of the reagents used for this manuscript. Other than this, the authors declare no competing interest. AbbreviationsCNVcopy number variantDDdevelopmental disorderDLE-1direct Labeling Enzyme-1DLSdirect Label and StainEDTAethylenediaminetetraacetic acidFISHfluorescence in situ hybridizationFSHDfacioscapulohumeral dystrophygDNAgenomic DNAIDintellectual disabilityi.e.id est (that is)MCAmultiple congenital malformationsNGSnext generation sequencingSVstructural variantUHMWultra-long high molecular weightWESwhole exome sequencingWGSwhole genome sequencing ER -