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Noninvasive prenatal screening at low fetal fraction: comparing whole‐genome sequencing and single‐nucleotide polymorphism methods
Author(s) -
Artieri Carlo G.,
Haverty Carrie,
Evans Eric A.,
Goldberg James D.,
Haque Imran S.,
Yaron Yuval,
Muzzey Dale
Publication year - 2017
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5036
Subject(s) - trisomy , aneuploidy , fetus , prenatal screening , snp , prenatal diagnosis , single nucleotide polymorphism , snp array , fraction (chemistry) , cell free fetal dna , biology , medicine , genetics , pregnancy , genotype , chromosome , chemistry , gene , organic chemistry
Objective Performance of noninvasive prenatal screening (NIPS) methodologies when applied to low fetal fraction samples is not well established. The single‐nucleotide polymorphism (SNP) method fails samples below a predetermined fetal fraction threshold, whereas some laboratories employing the whole‐genome sequencing (WGS) method report aneuploidy calls for all samples. Here, the performance of the two methods was compared to determine which approach actually detects more fetal aneuploidies. Methods Computational models were parameterized with up‐to‐date published data and used to compare the performance of the two methods at calling common fetal trisomies (T21, T18, T13) at low fetal fractions. Furthermore, clinical experience data were reviewed to determine aneuploidy detection rates based on compliance with recent invasive screening recommendations. Results The SNP method's performance is dependent on the origin of the trisomy, and is lowest for the most common trisomies (maternal M1 nondisjunction). Consequently, the SNP method cannot maintain acceptable performance at fetal fractions below ~3%. In contrast, the WGS method maintains high specificity independent of fetal fraction and has >80% sensitivity for trisomies in low fetal fraction samples. Conclusion The WGS method will detect more aneuploidies below the fetal fraction threshold at which many labs issue a no‐call result, avoiding unnecessary invasive procedures. © 2017 Counsyl Inc. Prenatal Diagnosis published by John Wiley & Sons, Ltd.