Chromosomal phase improves aneuploidy detection in non-invasive prenatal testing at low fetal DNA fractions.

ABSTRACT: Non-invasive prenatal testing (NIPT) to detect fetal aneuploidy by sequencing the cell-free DNA (cfDNA) in maternal plasma is being broadly adopted. To detect fetal aneuploidies from maternal plasma, where fetal DNA is mixed with far-larger amounts of maternal DNA, NIPT requires a minimum fraction of the circulating cfDNA to be of placental origin, a level which is usually attained beginning at 10 weeks gestational age. We present an approach that leverages the arrangement of alleles along homologous chromosomes-also known as chromosomal phase-to make NIPT analyses more conclusive. We validate our approach with in silico simulations, then re-analyze data from a pregnant mother who, due to a fetal DNA fraction of 3.4%, received an inconclusive aneuploidy determination through NIPT. We find

SUBMITTER: Genovese G 

PROVIDER: S-EPMC9283487 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature