Fetal fraction amplification within NIPS enables detection of clinically relevant genome-wide copy-number-variants to 1Mb resolution

Abstract

While clinically relevant copy number variants (CNVs) occur in 6-8% of pregnancies with fetal structural anomalies, they are typically difficult to detect via noninvasive prenatal screening (NIPS) because of the low fetal fraction in maternal cell-free DNA (cfDNA). By leveraging fetal fraction amplification, a method to preferentially sequence shorter fragments that are enriched for fetal-derived cfDNA, we can detect small CNVs with high sensitivity. Here we describe an analytical validation of an NIPS that can detect clinically relevant CNVs across the genome.