Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations.
Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations.
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扩大无创产前检测的范围以检测胎儿染色体拷贝数变异
DOI：
10.3389/fmolb.2021.649169
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发表时间：
2021
影响因子：
5
通讯作者：
Lu D
中科院分区：
文献类型：
--
作者：
Chen S;Zhang L;Gao J;Li S;Chang C;Chen Y;Fei H;Zhang J;Wang Y;Huang H;Xu C;Lu D
无创产前检测 (NIPT) 对于常见胎儿三体性是有效的。然而，人们对无细胞 DNA 检测检测其他染色体异常的有用性知之甚少。我们分析了下一代测序（NGS）中不同读取深度的阳性率，并确定了 NIPT 中胎儿拷贝数变异（CNV）检测的策略。通过羊膜穿刺术和染色体微阵列分析 (CMA) 对在 4-6 M 读取深度下接受 NGS NIPT 的孕妇和疑似 CNV 的胎儿进行分析。将这些胎儿样本以25 M的读取深度重新测序并确定阳性检出率。随着读取深度的增加，阳性CNV检出率增加。 NGS 检测 25 M 小片段 CNV 阳性检出率高于核型分析。增加 NGS 的读取深度可提高阳性 CNV 检测率，同时降低假阳性检测率。 NGS 进行的 NIPT 可能是一种准确的胎儿染色体分析方法，可降低出生缺陷率。
Non-invasive prenatal testing (NIPT) for common fetal trisomies is effective. However, the usefulness of cell-free DNA testing to detect other chromosomal abnormalities is poorly understood. We analyzed the positive rate at different read depths in next-generation sequencing (NGS) and identified a strategy for fetal copy number variant (CNV) detection in NIPT. Pregnant women who underwent NIPT by NGS at read depths of 4–6 M and fetuses with suspected CNVs were analyzed by amniocentesis and chromosomal microarray analysis (CMA). These fetus samples were re-sequenced at a read depth of 25 M and the positive detection rate was determined. With the increase in read depth, the positive CNV detection rate increased. The positive CNV detection rates at 25 M with small fragments were higher by NGS than by karyotype analysis. Increasing read depth in NGS improves the positive CNV detection rate while lowering the false positive detection rate. NIPT by NGS may be an accurate method of fetal chromosome analysis and reduce the rate of birth defects.