Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Med Genet. May 27, 2015; 5(2): 23-27
Published online May 27, 2015. doi: 10.5496/wjmg.v5.i2.23
Comparison of next generation sequencing-based and methylated DNA immunoprecipitation-based approaches for fetal aneuploidy non-invasive prenatal testing
Georgia Christopoulou, Elisavet A Papageorgiou, Philippos C Patsalis, Voula Velissariou
Georgia Christopoulou, Voula Velissariou, AlfaLab Cytogenetics and Molecular Biology Center, Hygeia Group, 115 24 Athens, Greece
Elisavet A Papageorgiou, NIPD Genetics Ltd., the Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus
Philippos C Patsalis, Ministry of Health, Government Office, Prodromou, 1448 Nicosia, Cyprus
Author contributions: All authors designed the structure and content of the manuscript; Christopoulou G wrote the manuscript; Papageorgiou EA and Velissariou V revised the manuscript; Patsalis PC and Velissariou V made the final revisions; all authors have read and approved the final manuscript.
Conflict-of-interest: Elisavet A Papageorgiou is currently employed by and owns shares of NΙPD Genetics. Philippos C Patsalis also owns shares of ΝΙPD Genetics. Elisavet A Papageorgiou and Philippos C Patsalis have filed a PCT patent application for the MeDΙP real time qPCR based NΙPD approach (PCT Patent Αpplication No.PCT/1B2011/Ο00217). Vοu1a Velissariou and Georgia Christopoulοu declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Voula Velissariou, PhD, Head of Cytogenetics, AlfaLab Cytogenetics and Molecular Biology Center, Hygeia Group, Anastassiou Str., 115 24 Athens, Greece.
Telephone: +30-210-6902096 Fax: +30-210-6902083
Received: January 24, 2015
Peer-review started: January 27, 2015
First decision: March 15, 2015
Revised: April 7, 2015
Accepted: April 16, 2015
Article in press: April 20, 2015
Published online: May 27, 2015

Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing (NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother’s plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing (NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.

Keywords: Next generation sequencing, Differential methylation, Epigenetics, Fetal aneuploidy, Methylation dependent immunoprecipitation, Non-invasive prenatal testing

Core tip: Non-invasive prenatal screening and diagnosis of fetal aneuploidies has been a challenging field for many researchers. Different methodologies have been developed, mainly based on next-generation sequencing and epigenetic modifications. At present, non-invasive prenatal testing services are offered using next generation sequencing-based technologies which have great potential, but currently they present with certain limitations. Epigenetic approaches may overcome some of these limitations and seem to have promising potential for wider applications.