Myriad Genetics was honored to participate in one of the most important conferences for Maternal Fetal Medicine specialists and other medical providers focused on the health of mothers, pregnancies, and babies. At the Society for Maternal-Fetal Medicine’s 42^nd Annual Pregnancy Meeting, Myriad Genetics gave a preview of new developments in the detection of chromosomal micro-deletions and micro-duplications which will soon be part of the Prequel^® Prenatal Screen.

In depth information about Prequel with AMPLIFY™ technology was shared at a Myriad sponsored industry symposium. Dale Muzzey, senior vice president, Research and Development, reviewed how traditional NIPS performance is negatively impacted by low fetal fraction. Biological factors such as high body-mass index (BMI), early gestational age, and other factors can reduce the resolution of the signal from the cell-free DNA (cfDNA) derived from the pregnancy, making it difficult to discern if an abnormality is present. Given that high BMI is more often found amongst certain ethnicities, this creates a disparity in equitable care.

Myriad’s Prequel test with AMPLIFY^TM technology addresses the limitations of low fetal fraction by preferentially sequencing shorter DNA fragments that are enriched for fetal-derived cfDNA. Increasing the fetal signal within a sample helps create a more equitable NIPS and reduces the needs for redraws and complicated workflows that go along with them.

As shared by Ashley Acevedo, bioinformatics scientist, one additional benefit of increasing the fetal fraction is the ability to enhance the detection of both chromosomal and sub-chromosomal abnormalities – allowing for the detection of small, yet clinically actionable, chromosome changes.¹

A recent study found that 17% of all chromosomal abnormalities detected were clinically-relevant sub-chromosomal changes that either covered a large portion of the chromosome or had a high degree of pathogenicity.² With AMPLIFY™ technology, these types of sub-chromosomal abnormalities can be more clearly detected. For example, on the chart below, a sub-chromosomal abnormality (light blue region) is hardly discernable despite the sample having 8.9% fetal fraction.

However, with AMPLIFY™ technology, the fetal fraction and the ability to detect the sub-chromosomal abnormality are both enhanced as shown in the graph below (light blue region).

As shown in the graph below using simulated data, for a given sub-chromosomal abnormality, the sensitivity sharply declines at a fetal fraction below 15%.³   Therefore, detection of sub-chromosomal abnormalities can be tailored depending on the fetal fraction. In other words, we can individualize chromosome resolution in relation to the amplified fetal fraction within a specific sample in order to maintain a high level of sensitivity – the higher the amplified fetal fraction, the smaller the sub-chromosomal changes that can be detected. This is an area of continued research. Initial results are very promising as shown in a poster, Fetal fraction amplification within NIPS enables detection of clinically relevant genome-wide copy number variants to 1Mb resolution, (insert link) presented at the SMFM 42^nd Annual Pregnancy Meeting.³  

Learn more about noninvasive prenatal screening:

• The impact of prenatal screening on parents and pregnancies
• Even before birth, genetic screening provides insights for family planning

1. Welker, N.C., et al. High-throughput fetal fraction amplification increases analytical performance of noninvasive prenatal screening. Genet Med 23, 443–450 (2021). https://doi.org/10.1038/s41436-020-01009-5
2. Lin YH, Jong YJ, Huang PC, Tsai C. Detection of copy number variants with chromosomal microarray in 10 377 pregnancies at a single laboratory. Acta Obstet Gynecol Scand. 2020;99(6):775-782. doi:10.1111/aogs.13886
3. Acevedo, A., et.al. (2022, January) Fetal fraction amplification within NIPS enables detection of clinically relevant genome-wide copy number variants to 1Mb resolution.  Poster presented at SMFM’s 42nd Annual Pregnancy Meeting.  Virtual