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Abstract：
Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM\'s concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of the NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.
摘要：
染色体分析（CA）和染色体微阵列分析（CMA）已成功用于诊断遗传疾病。然而,由于分辨率（CA）和仅检测不平衡事件（CMA）的限制，许多疾病仍未被诊断。光学基因组作图（OGM）有可能通过捕获两种结构变体（SV）来解决这些限制，从而导致拷贝数变化和高分辨率的平衡重排。在这项研究中,我们使用先前由CA鉴定的87个SV调查了OGM的一致性，CMA,或南方印迹。总的来说,OGM与仅三个不一致的病例具有98％的一致性：（1）在着丝粒中具有一个断点的未被提及的易位；（2）在伪常染色体区域1中具有断点的未被提及的重复；（3）源自标记染色体的未被提及的镶嵌三倍体。OGM为三个先前未解决的病例提供了诊断：（1）由于平衡的相互易位导致SON基因的破坏；（2）由于反向插入导致NBEA基因的破坏；（3）由于镶嵌缺失导致TSC2基因的破坏。我们表明，OGM是一种有效的方法，用于检测许多类型的SVs在一个单一的测定，是高度一致的与传统的细胞基因组方法;然而，它在着丝粒和伪常染色体区域的SV检测能力有限。
