Validation Studies for Single Circulating Trophoblast Genetic Testing as a Form of Noninvasive Prenatal Diagnosis

It has long been appreciated that genetic analysis of fetal or trophoblast cells in maternal blood could revolutionize prenatal diagnosis. We implemented a protocol for single circulating trophoblast (SCT) testing using positive selection by magnetic-activated cell sorting and single-cell low-covera...

Full description

Saved in:
Bibliographic Details
Published in:American journal of human genetics 2019-12, Vol.105 (6), p.1262-1273
Main Authors: Vossaert, Liesbeth, Wang, Qun, Salman, Roseen, McCombs, Anne K., Patel, Vipulkumar, Qu, Chunjing, Mancini, Michael A., Edwards, Dean P., Malovannaya, Anna, Liu, Pengfei, Shaw, Chad A., Levy, Brynn, Wapner, Ronald J., Bi, Weimin, Breman, Amy M., Van den Veyver, Ignatia B., Beaudet, Arthur L.
Format: Article
Language:English
Subjects:
Adult
cell-based NIPT
Chromosome Disorders - diagnosis
Chromosome Disorders - genetics
DNA Copy Number Variations
Female
fetal
Genetic Markers
Humans
Male
mosaisicm
noninvasive prenatal diagnosis
Noninvasive Prenatal Testing - methods
Placenta - cytology
Placenta - metabolism
Pregnancy
Single-Cell Analysis
trophoblast
Trophoblasts - cytology
Trophoblasts - metabolism
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:It has long been appreciated that genetic analysis of fetal or trophoblast cells in maternal blood could revolutionize prenatal diagnosis. We implemented a protocol for single circulating trophoblast (SCT) testing using positive selection by magnetic-activated cell sorting and single-cell low-coverage whole-genome sequencing to detect fetal aneuploidies and copy-number variants (CNVs) at ∼1 Mb resolution. In 95 validation cases, we identified on average 0.20 putative trophoblasts/mL, of which 55% were of high quality and scorable for both aneuploidy and CNVs. We emphasize the importance of analyzing individual cells because some cells are apoptotic, in S-phase, or otherwise of poor quality. When two or more high-quality trophoblast cells were available for singleton pregnancies, there was complete concordance between all trophoblasts unless there was evidence of confined placental mosaicism. SCT results were highly concordant with available clinical data from chorionic villus sampling (CVS) or amniocentesis procedures. Although determining the exact sensitivity and specificity will require more data, this study further supports the potential for SCT testing to become a diagnostic prenatal test.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2019.11.004