Researchers have sequenced the entire genome of an 18 and a half-week-old
fetus using DNA samples from the blood of its mother and saliva samples from
its father. These findings provide a proof of principle that a fetus can be
examined for genetic conditions using non-invasive technologies.
Currently, non-invasive screening is used to detect conditions where
there is an extra copy of a chromosome, known as trisomy - including Down's
syndrome, where there are three copies of chromosome 21.
This study, published in Science Translational Medicine, shows that it
is possible to non-invasively sequence the whole genome of a fetus and to use
that to check for smaller changes in the DNA, including more than 3000 single gene disorders.
'If the genome is a book, and a trisomy is an extra chapter, we want to
find every typo', lead researcher Dr Jay Shendure of the University of
Washington in Seattle told New Scientist.
Single gene, or Mendelian, disorders affect around one
percent of live births, and include cystic fibrosis and Huntington's disease.
Currently, a small number of specific Mendelian disorders are screened for during
pregnancy, but this requires the use of invasive procedures that increase the
risk of miscarriage
The team of researchers, primarily based at the University of
Washington, exploited the fact that around 13 percent of DNA in a pregnant
woman's blood plasma - known as cell-free DNA - originates from the fetus.
Looking for small variations in the letters of the genetic code, they compared
the sequence of the cell-free DNA to the mother's DNA, which was sequenced from
a blood sample, and so would be 100 percent her own. Any variants found in the
cell-free DNA but not in the DNA from the mother's blood were assumed to have
come from the fetus.
Further confirmation that these were sections of DNA from the fetus was
made by comparing variants to the father's DNA, which was sequenced from a
saliva sample. Variants unique to him that appeared in the cell-free DNA must
have been inherited by the fetus.
After birth, the baby's genome was sequenced from cord blood, showing
their predictions were 98 percent accurate. They also tested their techniques
on a second pregnant woman with an 8.2-week-old fetus, with 95 percent
accuracy, which suggests these methods could be used to screen very young fetuses.
As well as heritable variants, the researchers looked for spontaneous
mutations, identifying 39 of the 44 that were discovered after birth. However,
both the New York Times and Science Now reported that they also identified 25
million false positives.
Dr Shendure suggested that the technique could be available in the
clinic within five years, estimating the cost at $50,000 per child. However, he
warned that the ability to read the genome and find genetic variants far out-strips
our ability to understand the consequences on the development and health of a
child. 'There will be many mutations whose impact we just don't know', he told
Professor Dennis Lo, the pathologist who first discovered that fetal DNA circulates
in the mother's blood, has urged caution. Speaking to Science Now, he said: 'I
don't think it would be ethical to use this to screen for late-onset diseases
like Alzheimer's or cardiovascular diseases, for example'.