Abstract：
Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.
摘要：
低通全基因组测序(LP-WGS)已被用作在临床环境中检测拷贝数变体(CNV)的替代方法。与染色体微阵列分析（CMA）相比，基于测序的方法以较低的成本提供了类似的CNV检测分辨率.在这项研究中,我们评估了LP-WGS作为CMA更实惠的替代方案的效率和可靠性.共有1363名原因不明的神经发育迟缓/智力障碍患者，自闭症谱系障碍，和/或多种先天性异常纳入研究。这些患者来自巴西不同州的15个非营利组织和大学中心。在1x覆盖率（>50kb）的LP-WGS分析显示22％的病例（304/1363）的阳性检测结果，其中219和85对应于致病性/可能致病性（P/LP）CNVs和不确定意义（VUS）的变体，分别。在我们的队列中观察到的16%(219/1363)诊断产率与文献中报道的CMA的15%-20%相当。使用商业软件，正如这项研究所证明的，简化了测试在临床环境中的实施。尤其是像巴西这样的国家，CMA的成本对大多数人口构成了巨大的障碍，LP-WGS成为研究细胞遗传学中拷贝数变化的经济有效的替代方案。
