normal pregnancies and in pregnancies in which the
fetus has trisomy 21. Consequently, neither human
chorionic gonadotrophin nor
α
-fetoprotein alone is
highly discriminatory for trisomy 21. However,
combination testing with the two markers is a fairly
reliably way to detect pregnancies that are at high
enough risk of trisomy 21 to justify the use of an
invasive technique of prenatal testing.
Fetal cells.
Amniotic fluid and placenta are
sources of fetal cells that can be sampled with
relative ease and safety. Amniotic cells are obtained
by amniocentesis. Chromosome analysis, biochemi-
cal studies, and molecular diagnostic studies can be
performed directly on the collected cells but, more
commonly, the studies are carried out on cells
obtained by tissue culture of the mitotically active
cells in the specimen.
Placental cells are obtained by chorionic villus
sampling. This technique involves suction biopsy of
a small amount of chorion frondosum, the progenitor
of the placenta. The yield of fetal DNA with this
procedure is often large enough to permit molecular
diagnostic studies to be performed directly on the
fetal cells contained in the specimen. Chromosome
analysis and biochemical studies are performed on
cells cultured from the mesenchymal core of the
villi. If necessary, molecular diagnostic studies can
be conducted on cultured cells rather than on directly
on the collected cells.
Chromosome analyses can also be conducted on
fetal lymphocytes cultured from fetal blood obtained
by percutaneous umbilical cord blood sampling.
The risk of pregnancy loss with this procedure is
greater than for amniocentesis or chorionic villus
sampling.
An extremely low risk source of fetal cells is
maternal blood. Starting late in the first trimester,
trophoblasts and fetal blood cells can be found in the
maternal circulation. The cells are present in very
low concentration but they can be concentrated using
various cell sorting techniques (Martin
et al.
1998).
Unfortunately, cell sorting does not produce a
homogenous fetal cell sample; maternal cells always
constitute a large fraction of the cells in the sorted
sample. Consequently, the material cannot be used
to diagnose recessive and X-linked genetic disorders
because molecular diagnostic studies cannot distin-
guish the mutant DNA of the mother from that of the
fetus. Dominant genetic disorders can be diagnosed
if the father carries the gene, but not if the mother
does. Post-sorting isolation of individual fetal cells
greatly extends the usefulness of this approach. It
permits the performance of single cell interphase
chromosome analysis by fluorescence
in situ
hybridi-
zation and single cell DNA analysis by high-
sensitivity molecular diagnostic techniques.
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