Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, 1090 Vienna, Austria.
Genes (Basel). 2021 Dec 8;12(12):1958. doi: 10.3390/genes12121958.
In recent years, optical genome mapping (OGM) has developed into a highly promising method of detecting large-scale structural variants in human genomes. It is capable of detecting structural variants considered difficult to detect by other current methods. Hence, it promises to be feasible as a first-line diagnostic tool, permitting insight into a new realm of previously unknown variants. However, due to its novelty, little experience with OGM is available to infer best practices for its application or to clarify which features cannot be detected. In this study, we used the Saphyr system (Bionano Genomics, San Diego, CA, USA), to explore its capabilities in human genetic diagnostics. To this end, we tested 14 DNA samples to confirm a total of 14 different structural or numerical chromosomal variants originally detected by other means, namely, deletions, duplications, inversions, trisomies, and a translocation. Overall, 12 variants could be confirmed; one deletion and one inversion could not. The prerequisites for detection of similar variants were explored by reviewing the OGM data of 54 samples analyzed in our laboratory. Limitations, some owing to the novelty of the method and some inherent to it, were described. Finally, we tested the successful application of OGM in routine diagnostics and described some of the challenges that merit consideration when utilizing OGM as a diagnostic tool.
近年来，光学基因组图谱（OGM）已发展成为检测人类基因组中大规模结构变体的一种极有前途的方法。它能够检测到其他当前方法认为难以检测的结构变体。因此，它有望成为一种一线诊断工具，使人们能够深入了解以前未知的变体领域。然而，由于其新颖性，OGM 的应用经验很少，无法推断出最佳实践，也无法明确哪些特征无法检测到。在这项研究中，我们使用了 Saphyr 系统（Bionano Genomics，圣地亚哥，加利福尼亚州，美国），探索其在人类遗传诊断中的能力。为此，我们测试了 14 个 DNA 样本，以确认总共 14 种不同的结构或数值染色体变体，这些变体最初是通过其他方法检测到的，即缺失、重复、倒位、三体和易位。总体而言，有 12 个变体可以得到确认；有一个缺失和一个倒位无法确认。通过回顾我们实验室分析的 54 个样本的 OGM 数据，探索了检测类似变体的前提条件。描述了一些由于方法的新颖性和固有原因而产生的局限性。最后，我们测试了 OGM 在常规诊断中的成功应用，并描述了在将 OGM 用作诊断工具时值得考虑的一些挑战。
