Droplet digital PCR, a new approach to analyze fetal DNA from maternal blood: application to the determination of fetal RHD genotype

Ann Biol Clin (Paris). 2016 Jun 1;74(3):269-77. doi: 10.1684/abc.2016.1139.

Abstract

The discovery of free fetal DNA in the maternal circulation has inaugurated the era of non-invasive prenatal diagnosis. The latter has the advantage of avoiding the use of conventional obstetric procedures, such as chorionic villus sampling or aspiration of amniotic fluid, thus limiting the risks of miscarriage they induce. However, as free fetal DNA accounts for about 10% of cell-free DNA in maternal plasma, the presence of ambient maternal DNA can make it difficult to detect fetal alleles of paternal origin. Digital Droplet PCR (ddPCR) is a very sensitive method derived from quantitative real-time PCR (qPCR) for the detection of rare alleles and their absolute quantification by removing the necessity of standards. Here we show that this new technology can be applied in routine prenatal fetal RHD genotyping from maternal blood. In conclusion, the use of quantitative properties of digital PCR, in terms of accuracy, sensitivity and specificity, allows one to consider extending the applications of this new technology in non-invasive prenatal diagnosis of many diseases such as autosomal monogenic diseases, either dominant or recessive.

Keywords: RHD genotyping; droplet digital PCR; non-invasive prenatal diagnosis.

MeSH terms

  • Blood Chemical Analysis / methods
  • DNA / analysis*
  • DNA / metabolism
  • Female
  • Fetus / chemistry*
  • Fetus / metabolism
  • France
  • Genotype
  • Genotyping Techniques / methods
  • Humans
  • Maternal Serum Screening Tests / methods*
  • Mothers*
  • Pregnancy
  • Real-Time Polymerase Chain Reaction / methods*
  • Rh-Hr Blood-Group System / blood
  • Rh-Hr Blood-Group System / genetics*
  • Sensitivity and Specificity

Substances

  • Rh-Hr Blood-Group System
  • DNA