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Updated: Jun 5, 2026
FISH for Pre-implantation Genetic Diagnosis
Published on: February 23, 2011
Fetal fraction amplification within prenatal cfDNA screening enables detection of genome-wide copy-number variants at
Ashley Acevedo1, Oyang Teng1, Heather G LaBreche1
1Myriad Genetics, Inc, Salt Lake City, UT.
Purpose:
Clinically significant copy-number variants (CNVs) occur in 1% to 2% of pregnancies and are difficult to detect via prenatal cell-free DNA (cfDNA) screening because of the low fraction of fetal-derived cfDNA in maternal plasma. Here, we use fetal fraction amplification (FFA) and improved computational algorithms to enhance the resolution and sensitivity of CNV detection.
Methods:
We implemented and characterized the performance of a hidden Markov model that identifies fetal CNVs. This CNV caller was analytically validated on 117 FFA samples, including 57 fetal-CNV-containing samples, and applied retrospectively to a cohort of more than 300k patient samples.
Results:
Our assay was concordant with orthogonal testing and detected fetal CNVs ≥5 Mb with estimated aggregate sensitivity and specificity of >95.1% and >99.7%, respectively. The resolution of CNV detection was fetal fraction dependent, but 97.2% of samples reached ≥5-Mb resolution. Overall, CNVs ≥5 Mb were found in 1 in 500 pregnancies.
Conclusion:
FFA improves the sensitivity and resolution of CNV detection in prenatal cfDNA screening, allowing accurate detection of fetal CNVs as small as 1 Mb. Using our approach, we found that clinically significant fetal CNVs were detected more frequently than the common trisomies 13 and 18 that are recommended as part of guideline-based screening.
