Determination of fetal DNA fraction from the plasma of pregnant women using sequence read counts

Abstract

SeqFF is a robust and direct method to determine fetal DNA fraction. Furthermore, the method is applicable to both male and female pregnancies and can greatly improve the accuracy of noninvasive prenatal testing for fetal copy number variation.

Debates on fetal fraction measurement and DNA‐based noninvasive prenatal screening: time for standardisation?

“…Newly developed measurement assays for FF are increasingly accurate and not costly. 6 From the point of view of public health, a public screening test must be cost-effective in that it must take account of the balance between a higher detection rate and additional laboratory costs including administrative costs for recall. If offered as a private service, clients should be fully informed about different testing methods and their cost before making their decision.…”

“…5 MPS is a method for nonselective sequencing and analysis of all the circulating DNA of both maternal and fetal origin in maternal plasma, and it is technically possible to derive the FF in the same MPS assay with no additional cost. 6 There are also targeted approaches [chromosome-selective sequence analysis and single nucleotide polymorphism (SNP)-based analysis] which are directed against specific regions on the major chromosome of interest before sequence analysis. With technical modification, some commercial DNA laboratories that use the MPS approach can avoid reporting the incidental detection of other chromosomal abnormalities of unknown clinical relevance.…”

“…Kim et al 6 comparing their principles, the domain on the fetal-derived sequence that the assay is estimating, and the technical and clinical issues for each assay as well as the supporting literature. A summary of the different approaches to the measurement of FF adopted by major service laboratories is shown in Table 2.…”

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach

“…Currently, it is possible to measure the FF of cfDNA using different categories of fetus-specific or fetus-nonspecific markers: Y chromosomal markers, SNPs, DNA methylation markers, autosomal regional read counts, and the cfDNA fragment length/size [20,[31][32][33][34][35][36]. Ideally, the best method for detecting and quantifying the cfDNA fraction should be easy to perform, should not require additional assays, and should be applicable to all pregnancies in a gender-independent fashion.…”

“…Measurement of the FF with the Harmony TM Prenatal Test is based on an assay against a set of SNPs and is very accurate [19,20]. To assess the fetal DNA fraction, the Cerba test uses a multivariate regression model based on subtle fragment length differences and the inferred nonuniformity of fetal cfDNA across the genome (SeqFF) as described by Kim et al [36].…”