PNAS:加开发出一种基于半导体的DNA测序平台改善胎儿遗传测试

科研人员报告了一种基于半导体的DNA测序平台可能有助于增加胎儿遗传测试的速度并减少成本。近来基于大规模平行测序的方法已经促进了迅速的、非侵入式的出生前遗传测试，这种测试通过分析母亲血浆中流动的无细胞DNA从而测试被称为非整倍性的染色体拷贝数的异常。

Kang Zhang及其同事开发了一种基于半导体的实验台测序平台，在2-4个小时里每秒获取50亿个数据点，因此也就增加了迅速、便携而且具有成本效益的胎儿非整倍性产前诊断的效率。

这组作者通过对515名孕妇测试诊断灵敏度和特异性从而验证了这个测序平台，这些孕妇来自中国的两所医院，此前通过核型分析获得了她们的非整倍性数据。这组作者报告说，这个平台发现了全部55例唐氏综合征、16例爱德华综合征、3例Patau综合征——它们的特点都是有额外的染色体拷贝——而特异性和灵敏度在99%到100%之间。

此外，这种方法帮助识别出了15名性染色体非整倍性的胎儿。之后，这组作者将这一平台应用到了1760名没有核型分析数据的孕妇身上，结果检测到了15例唐氏综合征、爱德华综合征或Patau综合征，以及1例x染色体非整倍性。这组作者说，这个平台可能为减少医院的灵敏而具有特异性的产前遗传诊断的时间和成本铺平了道路。

原文摘要：

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing

Can Liao, Ai-hua Yin, Chun-fang Peng, Fang Fu, Jie-xia Yang, Ru Li, Yang-yi Chen,Dong-hong Luo, Yong-ling Zhang, Yan-mei Ou, Jian Li, Jing Wu, Ming-qin Mai, Rui Hou,Frances Wu, Hongrong Luo, Dong-zhi Li, Hai-liang Liu, Xiao-zhuang Zhang andKang Zhang

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

作者：生物帮