Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy

Prenat Diagn. 2012 Jan;32(1):3-9. doi: 10.1002/pd.2922. Epub 2012 Jan 6.


Objective: To develop a novel prenatal assay based on selective analysis of cell-free DNA in maternal blood for evaluation of fetal Trisomy 21 (T21) and Trisomy 18 (T18).

Methods: Two hundred ninety-eight pregnancies, including 39 T21 and seven T18 confirmed fetal aneuploidies, were analyzed using a novel, highly multiplexed assay, termed digital analysis of selected regions (DANSR™). Cell-free DNA from maternal blood samples was analyzed using DANSR assays for loci on chromosomes 21 and 18. Products from 96 separate patients were pooled and sequenced together. A standard Z-test of chromosomal proportions was used to distinguish aneuploid samples from average-risk pregnancy samples. DANSR aneuploidy discrimination was evaluated at various sequence depths.

Results: At the lowest sequencing depth, corresponding to 204,000 sequencing counts per sample, average-risk cases where distinguished from T21 and T18 cases, with Z statistics for all cases exceeding 3.6. Increasing the sequencing depth to 410,000 counts per sample substantially improved separation of aneuploid and average-risk cases. A further increase to 620,000 counts per sample resulted in only marginal improvement. This depth of sequencing represents less than 5% of that required by massively parallel shotgun sequencing approaches.

Conclusion: Digital analysis of selected regions enables highly accurate, cost efficient, and scalable noninvasive fetal aneuploidy assessment.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 21 / genetics
  • Cost-Benefit Analysis
  • DNA / blood*
  • Down Syndrome / blood
  • Down Syndrome / diagnosis*
  • Down Syndrome / genetics
  • Female
  • Fetus
  • Genetic Testing / methods
  • Humans
  • Image Processing, Computer-Assisted
  • Pregnancy / blood*
  • Pregnancy Complications / diagnosis*
  • Pregnancy Complications / genetics
  • Prenatal Diagnosis / economics
  • Prenatal Diagnosis / methods*
  • Prospective Studies
  • Reproducibility of Results
  • Trisomy / diagnosis*
  • Trisomy / genetics


  • DNA