Prenatal Diagnosis Innovation: Genome Sequencing of Maternal Plasma

Annu Rev Med. 2016;67:419-32. doi: 10.1146/annurev-med-091014-115715. Epub 2015 Oct 15.


Noninvasive prenatal testing (NIPT) is accomplished by analysis of circulating cell-free fetal nucleic acids in maternal plasma. The advent of massively parallel sequencing (MPS) has enabled NIPT of chromosomal aneuploidies with unprecedented robustness, and these tests are now widely available for clinical use. Moreover, MPS-based NIPT of subchromosomal deletions/duplications and single-gene disorders has also been achieved, and the number of applications is growing. In addition to specific fetal genetic disorders, the whole fetal genome, transcriptome, and methylome have been revealed by deep sequencing of maternal plasma. The analysis of the fetal transcriptome and methylome may yield valuable information on fetal and maternal health. With continued improvement in sequencing technology and reduction in sequencing costs, the analysis of cell-free nucleic acids would play an increasingly important role in prenatal screening, diagnosis, monitoring, and risk stratification of fetal as well as maternal conditions.

Keywords: cell-free DNA; methylome; next-generation sequencing; noninvasive prenatal testing; transcriptome.

Publication types

  • Review

MeSH terms

  • Aneuploidy
  • DNA / blood*
  • DNA Methylation
  • DNA Mutational Analysis
  • Fetal Diseases / diagnosis*
  • Fetal Diseases / genetics*
  • Genetic Testing / methods*
  • Genome, Human*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Polymorphism, Single Nucleotide
  • Prenatal Diagnosis / methods*
  • Transcriptome


  • DNA