Microarray-Based Cell-Free DNA Analysis Improves Noninvasive Prenatal Testing

作者：Juneau Kara^*; Bogard Patrick E; Huang Stephanie; Mohseni Morassa; Wang Eric T; Ryvkin Paul; Kingsley Christopher; Struble Craig A; Oliphant Arnold; Zahn Jacob M

来源：Fetal Diagnosis and Therapy, 2014, 36(4): 282-286.

DOI：10.1159/000367626

• Aneuploidy
• Down syndrome
• Fetal diagnosis
• First trimester
• Noninvasive prenatal diagnosis
• Prenatal diagnosis
• Prenatal screening
• Trisomy 13
• Trisomy 18
• Trisomy 21

Objective: To develop a microarray-based method for non-invasive 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 (DANSR(TM)) 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 (FORTE(TM)) 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.

• 出版日期2014