Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Clin Chem. 2013 Aug;59(8):1228-37. doi: 10.1373/clinchem.2013.203679. Epub 2013 Apr 19.
With the advent of massively parallel sequencing (MPS), DNA analysis can now be performed in a genomewide manner. Recent studies have demonstrated the high precision of MPS for quantifying fetal DNA in maternal plasma. In addition, paired-end sequencing can be used to determine the size of each sequenced DNA fragment. We applied MPS in a high-resolution investigation of the clearance profile of circulating fetal DNA.
Using paired-end MPS, we analyzed serial samples of maternal plasma collected from 13 women after cesarean delivery. We also studied the transrenal excretion of circulating fetal DNA in 3 of these individuals by analyzing serial urine samples collected after delivery.
The clearance of circulating fetal DNA occurred in 2 phases, with different kinetics. The initial rapid phase had a mean half-life of approximately 1 h, whereas the subsequent slow phase had a mean half-life of approximately 13 h. The final disappearance of circulating fetal DNA occurred at about 1 to 2 days postpartum. Although transrenal excretion was involved in the clearance of circulating fetal DNA, it was not the major route. Furthermore, we observed significant changes in the size profiles of circulating maternal DNA after delivery, but we did not observe such changes in circulating fetal DNA.
MPS of maternal plasma and urinary DNA permits high-resolution study of the clearance profile of circulating fetal DNA.
随着高通量测序（MPS）的出现，现在可以对基因组进行 DNA 分析。最近的研究表明，MPS 可以高精度地定量母体血浆中的胎儿 DNA。此外，双端测序可用于确定每个测序 DNA 片段的大小。我们应用 MPS 对循环胎儿 DNA 的清除曲线进行了高分辨率研究。
我们使用双端 MPS 分析了 13 名剖宫产妇女产后的连续血浆样本。我们还通过分析产后连续的尿液样本，研究了其中 3 名个体的循环胎儿 DNA 的跨肾排泄情况。
循环胎儿 DNA 的清除呈两相，动力学不同。初始快速相的平均半衰期约为 1 小时，而随后的缓慢相的平均半衰期约为 13 小时。产后约 1 至 2 天，循环胎儿 DNA 最终消失。尽管跨肾排泄参与了循环胎儿 DNA 的清除，但并非主要途径。此外，我们在产后观察到循环母体 DNA 的大小谱发生了显著变化，但在循环胎儿 DNA 中未观察到这种变化。
对母体血浆和尿液 DNA 的 MPS 允许对循环胎儿 DNA 的清除曲线进行高分辨率研究。
