Noninvasive prenatal testing to analyze the fetal genome
Year: 2016
Type: article
Abstract: Prenatal genetic testing has changed markedly since the original introduction of amniocentesis as a means to evaluate the fetal karyotype. Because it has long been recognized that maternal age is highly associated with risk for Down syndrome, maternal age became the first screening test for aneuploidy. Later development of screening with maternal serum analytes and nuchal translucency ultrasound all led to improvements in prenatal genetic testing, with higher detection rates and lower screen-positive rates. The past decade has seen further advances with the discovery of cell-free fetal DNA (cfDNA) in the maternal circulation and development of sequencing and bioinformatics analytic approaches to very accurately assess the risk of Down syndrome. In 2011, this culminated in the clinical introduction of noninvasive prenatal testing (NIPT) for aneuploidy using cfDNA (1). With very-high sensitivity and very-low false-positive rates, this advance represented a tremendous step forward in Down syndrome detection. Subsequently, with higher depth of sequencing and improved bioinformatics analyses, NIPT expanded to include detection of a number of microdeletions (2, 3). Genome-wide screening for copy number variants has also been reported and is now offered clinically (4, 5). Noninvasive identification of fetal single-gene disorders, and ultimately analysis of the fetal genome, has become the “next frontier” in prenatal diagnosis (6) (Fig. 1).
Fig. 1.
An overview of currently available applications of massively parallel sequencing-based noninvasive prenatal testing using cell-free nucleic acids (DNA and RNA) in maternal plasma thought to originate from apoptotic trophoblasts. The fetal genome (from chromosomal to subchromosomal to single-gene levels) may be decoded; the methylome …
[↵][1]1Email: Mary.Norton{at}ucsf.edu.
[1]: #xref-corresp-1-1
Author: Mary E. Norton
Institution: University of California, San Francisco
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2559350045