""These samples were measured using multiple technologies including matrix-assisted laser desorption/ionization–timeof- flight mass spectrometry and massively parallel sequencing. Using these methods, 28 of the 30 aneuploid samples were detected with a specificity ranging from 0.95 to 0.99, depending on the chromosome.""
Selective Enrichment of Genomic Loci for the
Noninvasive Detection of Fetal Aneuploidies 
Taylor J. Jensen, PhD
Sequenom, San Diego, CA
Cosmin Deciu, MS, Mathias Ehrich, MD, Jennifer Geis, PhD,
Sung K. Kim, PhD, and Helen Tao, MS
INTRODUCTION: Current commercial offerings for noninvasive
prenatal testing differ in the breadth of their coverage (whole genome
or reduced content). Although whole genome methods provide an
unbiased view of the entire genome and thus the potential detection of
a broad array of genomic aberrations, reduced content methods
provide efficiency for detecting a limited set of copy number
variations. The objective of this study was to develop and evaluate
a noninvasive prenatal testing assay focused on the selective enrichment
and analysis of a subset of the genome.
METHODS: Regions for evaluation were selected using a combination
of bioinformatic and experimental methods. Circulating cell-free
DNA was extracted from the plasma of pregnant donors and amplified
using multiplexed amplification in a single well targeting more than 50
genomic loci. Amplified products were then evaluated using multiple
methods including matrix-assisted laser desorption/ionization–time-offlight
mass spectrometry and massively parallel sequencing.
RESULTS: We evaluated the performance of the developed assay in
an unblinded set of 288 circulating cell-free DNA samples from pregnant
donors with known fetal karyotypes including 258 euploid and 30
aneuploid samples. These samples were measured using multiple
technologies including matrix-assisted laser desorption/ionization–timeof-
flight mass spectrometry and massively parallel sequencing. Using
these methods, 28 of the 30 aneuploid samples were detected with a specificity
ranging from 0.95 to 0.99, depending on the chromosome.
CONCLUSION AND IMPLICATION: Taken together, these
proof-of-concept data demonstrate the feasibility of leveraging selected
genomic loci for a low-cost, platform-flexible method for the noninvasive
detection of fetal autosomal aneuploidies.
Financial Disclosure: Drs. Jensen, Ehrich, Geis, Kim, Tao, and den Boom
are employees of Sequenom Laboratories and shareholders of Sequenom, Inc. Dr.
Deciu is a shareholder of Sequenom, Inc.