美国Ariosa：微阵列芯片首次用于无创产前检测，比高通量测序更快更可靠

 《Fetal Diagnosis and Therapy》9月15日报道了美国Ariosa Diagnostics公司通过微阵列芯片（microarray）进行无创产前检测（Non-Invasive Prenatal Test，NIPT)的研究成果。Ariosa的CEO Ken Song表示，这是微阵列芯片首次被应用于NIPT领域。目前，Ariosa的招牌产品Harmony Prenatal Test以及市场上的其它NIPT产品均采用高通量测序技术对母体血浆中的胎儿游离DNA片段进行定量分析，从而评估胎儿患有染色体非整倍体疾病（21-三体、18-三体和13-三体）的风险。

据报道，Ariosa的研究人员通过DANSR（Digital Analysis of Selected Regions）分析878份母体血浆中游离DNA的指定染色体区域（21、18和13号染色体），并通过FORTE（Fetal-Fraction Optimized Risk of Trisomy Evaluation）算法评估胎儿患有染色体非整倍体疾病（21-三体、18-三体和13-三体）的风险。在对游离DNA进行定量检测时，他们分别采用了高通量测序和微阵列芯片（由Affymetirx定制）两种方法。研究结果显示，通过这两种方法所得到的染色体非整倍体判读结果完全一致。与高通量测序相比，微阵列芯片检测结果的差异性更低（0.051 versus 0.099，p<0.0001），但是分析时间由56小时缩短至7.5小时。此外，由于微阵列芯片可以检测更多的多态性位点，母体血浆游离DNA中胎儿成分的精确度提升了1.6倍（p<0.0001）。该研究结果显示，基于微阵列芯片的NIPT可以在更短的时间内获得更可靠的检测结果。

原文标题：Microarray-Based Cell-Free DNA Analysis Improves Noninvasive Prenatal Testing

原文摘要：
  Objective: To develop a microarray-based method for noninvasive prenatal testing (NIPT) and compare it with next generation sequencing.
  Methods: Maternal plasma from 878 pregnant women, including 187 trisomy cases (18 trisomy 13, 37 trisomy 18, 132 trisomy 21), was evaluated for trisomy risk. Targeted chromosomes were analyzed using Digital Analysis of Selected Regions (DANSRTM) assays. DANSR products were subsequently divided between two DNA quantification methods: microarrays and next-generation sequencing. For both microarray and sequencing methodologies, the Fetal-Fraction Optimized Risk of Trisomy Evaluation (FORTETM) algorithm was used to determine trisomy risk, assay variability across samples, and compute fetal fraction variability within samples.
  Results: NIPT using microarrays provided faster and more accurate cell-free DNA (cfDNA) measurements than sequencing. The assay variability, a measure of variance of chromosomal cfDNA counts, was lower for microarrays than for sequencing, 0.051 versus 0.099 (p < 0.0001). Analysis time using microarrays was faster, 7.5 versus 56 h for sequencing. Additionally, fetal fraction precision was improved 1.6-fold by assaying more polymorphic sites with microarrays (p < 0.0001). Microarrays correctly classified all trisomy and nontrisomy cases.
  Conclusions: NIPT using microarrays delivers more accurate cfDNA analysis than next-generation sequencing and can be performed in less time.

原文链接：http://www.karger.com/Article/FullText/367626