Uncertainty of fetal fraction determination in Non-Invasive Prenatal Screening by highly polymorphic SNPs

J Biotechnol. 2019 Jun 20:299:32-36. doi: 10.1016/j.jbiotec.2019.04.020. Epub 2019 Apr 26.

Abstract

Fetal fraction and the chromosome representation are the two key quantities used in Non-Invasive Prenatal Screening (NIPS) to determine the aneuploidy status of a fetus. Several methods for fetal fraction determination have been proposed in the literature, including a class of the methods, denoted snpFF, based on high-coverage targeted sequencing of highly polymorphic Single Nucleotide Polymorphisms (SNPs). The variant of snpFF, investigated here, has similar properties as the other variants of snpFF. We point out that the variability of the individual informative SNPs-based estimates of fetal fraction increases with the increase of fetal fraction. At 4% fetal fraction the Inter-Quartile Range (IQR) of the individual estimates of fetal fraction is around 3% and it increases to 6% at 15% fetal fraction. snpFF cannot detect fetal fraction below 2.5% because the number of informative SNPs becomes too small, even zero.

Keywords: Fetal fraction; NIPS; Single nucleotide polymorphism.

Publication types

  • Comparative Study

MeSH terms

  • Aneuploidy
  • Cell-Free Nucleic Acids / analysis
  • Female
  • Fetus / chemistry
  • Genetic Testing / methods*
  • Gestational Age
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Sequence Analysis, DNA / methods

Substances

  • Cell-Free Nucleic Acids