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

• Published in: Journal of biotechnology Vol. 299; pp. 32 - 36
• Main Authors: Grendár, Marian, Loderer, Dušan, Laučeková, Zuzana, Švecová, Iveta, Hrtánková, Michaela, Hornáková, Andrea, Nagy, Bálint, Žúbor, Pavol, Lasabová, Zora, Danko, Ján
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20-06-2019
• Subjects: Fetal fraction; NIPS; Single nucleotide polymorphism; WGS; QC; SNP; cfDNA; Fetal fraction; BAF; NIPS; IQR; Single nucleotide polymorphism
• ISSN: 0168-1656; 1873-4863
• DOI: 10.1016/j.jbiotec.2019.04.020

•There are several methods for determining fetal fraction, including snpFF.•snpFF is based on targeted sequencing of highly polymorphic SNPs.•Individual SNP-level variability of fetal fraction is rather high.•Uncertainty of snpFF increases with fetal fraction.•snpFF cannot reliably measure fetal fraction below 2.5%.
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.