Holesova Zuzana, Budis Jaroslav, Kucharik Marcel, Gazdarica Juraj, Carska Daria, Minarik Gabriel, Hyblova Michaela, Szemes Tomas
Geneton Ltd, Bratislava, Slovakia.
Comenius University Science Park, Bratislava, Slovakia.
PLoS One. 2025 Jul 11;20(7):e0327714. doi: 10.1371/journal.pone.0327714. eCollection 2025.
Non-invasive prenatal testing (NIPT) has revolutionized prenatal diagnostics by providing a safer alternative to invasive techniques such as amniocentesis and chorionic villus sampling. NIPT detects chromosomal abnormalities through the analysis of cell-free fetal DNA (cffDNA) in maternal plasma. One of the critical factors influencing accuracy of NIPT is the fetal fraction (FF) - the proportion of fetal cell-free DNA relative to total cell-free DNA in maternal plasma. This study investigates the potential of using telomere length measurements as a novel biomarker for fetal fraction prediction in NIPT. Telomere-derived fragments, which differ between maternal and fetal DNA, may serve as a measure of FF due to the distinct telomere length. Specifically, deviations from the expected shorter telomere lengths of maternal DNA toward longer lengths could be more pronounced at higher FF levels. Various models incorporating telomere content and features selected by Ordinary Least Squares (OLS) were evaluated to enhance fetal fraction prediction. Our results showed that telomere content also works as an independent predictor (with Pearson correlation 0.23), yielding a small improvement in prediction precision when combined with traditional models.
无创产前检测（NIPT）通过提供一种比羊膜穿刺术和绒毛取样等侵入性技术更安全的替代方法，彻底改变了产前诊断。NIPT通过分析母体血浆中的游离胎儿DNA（cffDNA）来检测染色体异常。影响NIPT准确性的关键因素之一是胎儿游离DNA比例（FF），即胎儿游离DNA相对于母体血浆中总游离DNA的比例。本研究探讨了使用端粒长度测量作为NIPT中预测胎儿游离DNA比例的新型生物标志物的潜力。由于端粒长度不同，母体和胎儿DNA中的端粒衍生片段可能作为FF的一种衡量指标。具体而言，在较高的FF水平下，母体DNA预期较短的端粒长度向较长长度的偏差可能会更加明显。评估了各种结合端粒含量和通过普通最小二乘法（OLS）选择的特征的模型，以提高胎儿游离DNA比例的预测能力。我们的结果表明，端粒含量也可作为独立预测指标（皮尔逊相关系数为0.23），与传统模型结合时，预测精度略有提高。
