November 19, 2023

What Does Fetal Fraction Mean?

Cell-free DNA originating from both the mother and fetus is found circulating in maternal plasma after seven weeks of gestation. It is referred to as cell-free fetal DNA (cffDNA). Circulating cffDNA can be isolated from the blood using next generation sequencing. The proportion of cffDNA that is derived from the fetus is called fetal fraction (FF) and can vary between under 4% to over 30%. Screening performance using cffDNA improves with increasing FF, and samples with low FF tend to yield indeterminate or no-call results. Therefore, improving FF is key to the successful implementation of NIPT.

Fetal DNA is usually characterized by fragment lengths that differ from those of the mother. The FF can be estimated by measuring the length of these differences. Figure 1 shows a plot of the length distribution for different values of fetal fraction. The peak at the left of the graph represents the region where the length of a DNA fragment overlaps with the size range of a fetus-derived fragment.

A number of methods have been developed for estimating the FF, including based on reads from the fetus’s Y chromosome. However, the accuracy of these methods has not been satisfactory.

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