Noninvasive prenatal molecular karyotyping from maternal plasma

PLoS One. 2013 Apr 17;8(4):e60968. doi: 10.1371/journal.pone.0060968. Print 2013.


Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal microdeletions from maternal plasma using massively parallel sequencing have been reported. However, these previous reports were either polymorphism-dependent or used statistical analyses which were confined to one or a small number of selected parts of the genome. In this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb resolution across the whole genome through the massively parallel sequencing of maternal plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In three cases, fetal microdeletions have been detected successfully from maternal plasma. In two cases, fetal microduplications have been detected successfully from maternal plasma. In the remaining case, the plasma DNA sequencing result was consistent with the pregnant mother being a carrier of a microduplication. Simulation analyses were performed for determining the number of plasma DNA molecules that would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular karyotyping from maternal plasma by massively parallel sequencing is feasible and would enhance the diagnostic spectrum of noninvasive prenatal testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing / genetics
  • Chromosome Deletion
  • Chromosome Duplication
  • Chromosomes, Human / genetics
  • Computer Simulation
  • DNA / blood*
  • DNA / genetics
  • DNA Copy Number Variations
  • Female
  • Fetus / metabolism
  • Genome, Human / genetics
  • Humans
  • Karyotyping / methods*
  • Mothers*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Statistics as Topic


  • DNA

Grant support

This work was supported by University Grants Committee of the Government of the Hong Kong Special Administrative Region, under the Areas of Excellence Scheme (AoE/M-04/06); Hong Kong Research Grants Council General Research Fund (CUHK 463710); Sponsored Research Agreement from Sequenom Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.