Аннотация:Concerns of traditional prenatal aneuploidy testing methods, such as low
accuracy of noninvasive and health risks associated with invasive procedures,
were overcome with the introduction of novel noninvasive methods based on
genetics (NIPT). These were rapidly adopted into clinical practice in many
countries after a series of successful trials of various independent submethods.
Here we present results of own NIPT trial carried out in Moscow, Russia. 1012
samples were subjected to the method aimed at measuring chromosome
coverage by massive parallel sequencing. Two alternative approaches are
ascertained: one based on maternal/fetal differential methylation and another
based on allelic difference. While the former failed to provide stable results, the
latter was found to be promising and worthy of conducting a large-scale trial.
One critical point in any NIPT approach is the determination of fetal cell-free
DNA fraction, which dictates the reliability of obtained results for a given
sample. We show that two different chromosome Y representation
measures—by real-time PCR and by whole-genome massive parallel
sequencing—are practically interchangeable (r=0.94). We also propose a novel
method based on maternal/fetal allelic difference which is applicable in
pregnancies with fetuses of either sex. Even in its pilot form it correlates well
with chromosome Y coverage estimates (r=0.74) and can be further improved
by increasing the number of polymorphisms.