IRCCS Mondino Foundation, 27100 Pavia, Italy.
Department of Neuromuscular Diseases, University College London, London WC1N 3BG, UK.
Biomolecules. 2023 Oct 19;13(10):1546. doi: 10.3390/biom13101546.
A recessive Short Tandem Repeat expansion in has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients' blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method.
已发现 中的隐性短串联重复扩展与小脑共济失调、周围神经病和前庭反射消失综合征（CANVAS）有关，是迟发性共济失调和感觉性周围神经病的常见病因。这些扩展的常用大小确定程序基于 Southern Blotting（SB），这是一种耗时且相对不精确的技术。在本文中，我们将 SB 与光学基因组映射（OGM）进行比较，OGM 是一种基于荧光标记探针之间距离测量来检测结构变异（SV）的方法，用于诊断 CANVAS 和疾病谱。这两种方法应用于 17 名 CANVAS 患者的血液样本，并比较了结果大小，显示出良好的一致性。此外，长读测序用于两名患者，以研究与 SB 或 OGM 大小的一致性。我们的研究得出结论，OGM 代表了 SB 的可行替代方法，允许使用更简单的技术、更精确的扩展大小和扩展整个基因组中 SV 分析的能力，而 SB 是一种针对特定基因座的方法。
