J Korean Med Assoc.  2015 Nov;58(11):995-1002. 10.5124/jkma.2015.58.11.995.

Non-invasive prenatal test using cell free DNA

• Kim K

• KMID: 2195128
• DOI: http://doi.org/10.5124/jkma.2015.58.11.995

Abstract

Although conventional prenatal screening tests for Down syndrome have been developed over the past 20 years, the positive predictive value of these tests is around 5%. Through these tests, many pregnant women have taken invasive tests including chorionic villi sampling and amniocentesis for confirming Down syndrome. Invasive test carries the risk of fetal loss at a low but significant rate. There is a large amount of evidence that non-invasive prenatal test (NIPT) using cell free DNA in maternal serum is more sensitive and specific than conventional maternal serum and/or ultrasound screening. Therefore implementing NIPT will increase aneuploidy detection rate and concurrently decrease fetal loss rate accompanying invasive test. More than 1,000,000 NIPT were performed globally since 2011. The uptake rate of NIPT is expected to increase more rapidly in the future. Moreover, as a molecular genetic technique advances, NIPT can be used for not only common aneuploidy screening but single gene disorder, microdeletion, and whole fetal genome sequencing. In this review, I will focus on the NIPT for common aneuploidies such as trisomy 13, 18, and 21.

Keyword

Down syndrome; Maternal serum screening tests; Cell free DNA; Non-invasive prenatal test

MeSH Terms

Amniocentesis
Aneuploidy
Chorionic Villi Sampling
DNA*
Down Syndrome
Female
Genome
Humans
Mass Screening
Maternal Serum Screening Tests
Molecular Biology
Pregnancy
Pregnant Women
Prenatal Diagnosis
Trisomy
Ultrasonography
DNA

Figure

• 

  Figure 1 Classification of non-invasive prenatal test (NIPT). cfDNA, cell free DNA; S-MPS, shotgun massively parallel sequencing; T-MPS, targeted massively parallel sequencing; SNP, single nucleotide polymorphism; BGI, Beijing Genomics institute.

• 

  Figure 2 Principle of single nucleotide polymorphism method. SD, standard deviation; cfDNA, cell free DNA.

• 

  Figure 3 Simplified principle of single nucleotide polymorphism (SNP) based non-invasive prenatal test. Each dot is one SNP and is the sum of both the maternal and fetal contribution. SNPs are biallelic and thus have only 1 of 2 DNA bases possible (which we reference as A and B). The SNPs are only 1 per location going left to right (like the chromosome was lying on its side), total about 3,000 SNPs per chromosome (you could see this if it were spread out more). Top of profile is 100% A 0% B. Continuing to go down the profile, A decreases and B increases until the bottom is 100% B and 0% A. RED SNPs are where mom is AA. The top line is where baby is also AA (thus 100% A). The second has 75% A and 25% B (baby AB). Green SNPs are where mom is AB. Again increasing B% from the 1st to third line. Blue SNPs are where mom is BB. Again increasing B% until the final line where baby and mom are 100% B. When the mother's SNP is heterozygous (Green SNP), an extra band appears when the fetus is trisomic. However, the band positions are dependent on allele frequency and fetal fraction. When the mother's SNP is homozygous (red and Blue SNP), one band is shifted when the fetus is trisomic. Amount of shift is dependent on allele frequency and fetal fraction. Not all SNP profile results are visually conclusive and thus why the algorithm is needed [20].

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