Ariosa Diagnostics Inc., Roche Sequencing Solutions Inc., San Jose, CA, USA.
Ultrasound Obstet Gynecol. 2018 Jun;51(6):813-817. doi: 10.1002/uog.19036. Epub 2018 May 3.
Various methods of fetal-fraction measurement have been employed in conjunction with different approaches to cell-free DNA testing for fetal aneuploidy. In this study, we determined the accuracy and reproducibility of fetal-fraction measurement using polymorphic assays that are incorporated into the test design as part of the Harmony® prenatal test and evaluated whether the single nucleotide polymorphisms selected for and used in these assays can be applied broadly to all patient populations.
Clinical maternal plasma samples were assayed using a custom microarray with Digital ANalysis of Selected Regions (DANSR) assays designed to cover non-polymorphic targets on chromosomes of interest for aneuploidy assessment (13, 18, 21, X and Y) and polymorphic targets for fetal-fraction assessment. In a consecutive series of 47 512 maternal plasma samples, fetal-fraction measurements based on polymorphic assays were compared with those from Y-sequence quantitation. Reproducibility was examined between first- and second-tube measurements for the same patient sample in 734 cases. The fraction of informative loci was calculated for 13 988 samples.
There was a strong correlation between fetal fractions determined using the polymorphic assays and using Y-chromosome sequence quantitation (r = 0.97). Fetal-fraction measurement between the first and second tubes was highly reproducible (r = 0.98). The fraction of informative loci observed in a clinical series was consistent with predictions based on assay design.
The method based on relative quantitation at polymorphic loci on a microarray is accurate and reproducible for fetal-fraction estimation and is equally informative across global populations. This study provides a useful benchmark for ensuring the reliability and accuracy of fetal-fraction measurement. © 2018 Roche Sequencing Solutions. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
在用于胎儿非整倍体检测的游离 DNA 检测中，各种胎儿比例测量方法与不同的方法结合使用。在这项研究中，我们通过整合到测试设计中的多态性检测来确定胎儿比例测量的准确性和可重复性，这些检测是 Harmony®产前测试的一部分，并评估了用于这些检测的单核苷酸多态性是否可以广泛应用于所有患者群体。
使用带有 Digital ANalysis of Selected Regions (DANSR) 检测的定制微阵列对临床孕妇血浆样本进行检测，这些检测设计用于覆盖非多态性目标，用于评估非整倍体的目标（13、18、21、X 和 Y）和用于评估胎儿比例的多态性目标。在连续的 47512 例孕妇血浆样本中，基于多态性检测的胎儿比例测量结果与 Y 序列定量结果进行了比较。在 734 例患者中，检查了同一患者样本的第一管和第二管测量之间的可重复性。对 13988 例样本计算了信息性基因座的分数。
使用多态性检测确定的胎儿比例与使用 Y 染色体序列定量确定的胎儿比例之间具有很强的相关性（r=0.97）。第一管和第二管之间的胎儿比例测量高度可重复（r=0.98）。在临床系列中观察到的信息性基因座分数与基于检测设计的预测一致。
基于微阵列上多态性位点相对定量的方法可准确且可重复地进行胎儿比例估算，并且在全球人群中同样具有信息性。本研究为确保胎儿比例测量的可靠性和准确性提供了有用的基准。® 由 John Wiley & Sons Ltd 代表国际妇产科超声学会出版。
