Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach
Low-pass whole-genome sequencing in clinical cytogenetics: a validated approach
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DOI：
10.1038/gim.2015.199
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发表时间：
2016-09-01
影响因子：
8.8
通讯作者：
Xu, Zhengfeng
中科院分区：
文献类型：
--
作者：
Dong, Zirui;Zhang, Jun;Xu, Zhengfeng
目的：染色体微阵列分析是检测拷贝数变异（CNV）产前和产后诊断的金标准。我们的目的是确定下一代测序（NGS）技术是否可以成为常规临床应用中CNV检测的替代方法;方法：使用低覆盖率全基因组测序管道对570名患者的多中心组进行全基因组CNV分析（> 50 kb）。将这些样品用于染色体分析; CNV（即，致病性CNVs，pCNVs）根据美国医学遗传学和基因组学学会指南进行分类。结果：总共检测了198例流产，37例死胎，149例产前和186例产后样本。我们的方法对549个样本（96.3%）产生了结果。除了119例非整倍体受试者外，还有103例pCNV在82个样本中识别出74个丢失和29个获得，诊断率为53.2%（95%置信区间：45.8，60.5）、14.7%（5.0，31.1）、28.5%（21.1，36.6）和30.1%（23.6，37.3）。嵌合现象的检出率低至25%。结论：采用高分辨率全基因组方法可诊断染色体疾病或微缺失/微重复综合征患者。我们的研究揭示了NGS促进遗传诊断的潜力，这在产前和产后组中并不明显。
Purpose: Chromosomal microarray analysis is the gold standard for copy-number variant (CNV) detection in prenatal and postnatal diagnosis. We aimed to determine whether next-generation sequencing (NGS) technology could be an alternative method for CNV detection in routine clinical application;Methods: Genome-wide CNV analysis (>50kb) was performed On a multicenter group of 570 patients using a low-coverage whole-genome sequencing pipeline. These samples were referred for chromosomal analysis; CNVs (i.e., pathogenic CNVs, pCNVs) were classified according to the American College of Medical Genetics and Genomics guidelines.Results: Overall, a total of 198 abortuses, 37 stillbirths, 149 prenatal, and 186 postnatal samples were tested. Our approach yielded results in 549 samples (96.3%). In addition to 119 subjects with aneuploidies, 103 pCNVs (74 losses and 29 gains) were identified in 82 samples, giving diagnostic yields of 53.2% (95% confidence interval: 45.8, 60.5), 14.7% (5.0, 31.1), 28.5% (21.1, 36.6), and 30.1% (23.6, 37.3) in each group, respectively. Mosaicism was observed at a level as low as 25%.Conclusions: Patients with chromosomal diseases or microdeletion/microduplication syndromes were diagnosed using a high-resolution genome-wide method. Our study revealed the potential of NGS to facilitate genetic diagnoses that were not evident in the prenatal and postnatal groups.