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June 7th, 2012
05:24 PM ET

Baby's DNA constructed before birth

Mom gave a blood sample. Dad spit. The entire genome of their fetus was born.

Researchers at the University of Washington have, for the first time, done a near-total genome sequence of a fetus in this way.  Scientists published the results of this study in the journal Science Translational Medicine, suggesting that thousands of genetic diseases could be detected in children while they are still in the fetal stage.

Everyone has two copies of the human genome: One inherited from their biological mother and one from the biological father. With technology that's being used for genetic sequencing these days, it's not possible to say which variants on the chromosome you inherited from which parent.

Scientists also sequenced the cell-free component of the mother's blood - called the plasma - where about 10% of the DNA circulating is from the child, and the other 90% is from the mother. That introduces some difficulty, since it's hard to tell exactly what comes from the child.

Currently at least some component of diagnosis for genetic disorders in certain circumstances is done using technologies such as amniocentesis, which involves taking a sample of the fluid in the sac that surrounds the fetus in the womb - the mother has to have a needle inserted into her uterus, which is a lot more complicated than a simple blood test and carries some health risks.

"This might reduce the need to do invasive testing for fetuses," said Jay Shendure, associate professor of genome sciences at the University of Washington.

The focus of the study was the genome of a fetus whose mother's blood sample was taken at 18 weeks. The analysis of her blood, the father's saliva and the plasma contributed to a nearly full picture of the fetus's genome.  This model showed that the fetus had 39 mutations that it had not inherited from either parent.

To confirm, researchers looked at the baby's umbilical cord blood after it was born. In comparing the constructed DNA (from mom & dad's samples) and this cord sample,  researchers found five additional mutations that hadn't come from the mother or the father.  On the whole, the baby's artificially constructed genome using material from the parents was more than 98% accurate.

Researchers repeated the procedure on a different couple. This time the mother was only eight weeks pregnant when she donated her sample, and the father submitted a blood sample, which was processed in the same way that the other father's saliva was. This resulted in a fetal genome sequence that was 92% accurate.

"We could have brought it higher just by sequencing her plasma more deeply," said Jacob Kitzman, lead study author and graduate research fellow at the University of Washington.

There are also parts of the genome that technology available today just cannot measure very well, Kitzman says, so that's partly why there's not a 100% accuracy here.

Is gender selection of a fetus ethical?

Eight weeks are, however, well before mothers are able to get amniocentesis, which is often used at around 16 weeks.

It took more than a month to get the results from the sequencing, which is a lot longer than would be ideal in a clinical situation, Kitzman noted. In order to become more widespread, the technique would have to be easier to administer, quicker and less expensive.

So how much does this cost? Right now, in the ballpark of $50,000, Shendure says - and while that seems like a lot, keep in mind that this whole process involved sequencing the genomes of the mother and the father, separately analyzing the plasma and then double-checking the result with a sequence from the child's umbilical cord.

The price tag for sequencing has dropped by 10,000 fold in the last five years, Shendure says, so he expects this fetal genome technique will also become less expensive over time.

In the long-term, the technique may even help garner new insights about genetic diseases, but more immediately it would be restricted to identifying the genetic disorders that we already understand, he said.

"Whether this is the sort of thing we would do on a widespread basis for all pregnancies, that’s an open question and a complex one," he said.

The complexity comes, of course, from the ethical issues that arise concerning parents who would selectively abort fetuses that are predestined for certain conditions.

The technology worries medical ethicist Harriet Washington, who fears parents could use genome sequencing to predict and selectively abort children that don't meet certain standards - not just for diseases, but for things like hair and eye color.

“If we don’t look at the dangers, if we adopt this Pollyanna attitude and only look at the benefits, then it’s really easy to end up in a situation where we are blindsided,” Washington said.

Perhaps one day, even intelligence scores or skills could be forecasted, creating a situation akin the movie "Gattaca" where babies are basically custom-created to suit the needs of parents who can afford the technology.

What do you think about all this? Share your thoughts in the comments.


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