For the first time, researchers have determined virtually the entire genome of a foetus using only a blood sample from the pregnant woman and a saliva specimen from the father.

Revolutionary technique: Jay Shendure, a professor at the University of Washington, supervised the research team.(The New York Times)

That would allow thousands of genetic diseases to be detected prenatally. But the ability to know so much about an unborn child is likely to raise serious ethical considerations as well. It could increase abortions for reasons that have little to do with medical issues and more to do with parental preferences for traits in children.

“It’s an extraordinary piece of technology, really quite remarkable," said Peter Benn, professor of genetics and developmental biology at the University of Connecticut, who was not involved in the work. “What I see in this paper is a glance into the future."

The paper, published on Wednesday in the journal Science Translational Medicine, was written by genome scientists at the University of Washington. They took advantage of new high-speed DNA sequencing and some statistical and computational acrobatics to deduce the DNA sequence of the foetus with about 98% accuracy.

The process is not practical, affordable or accurate enough for use now, experts said. The University of Washington researchers estimated that it would cost $20,000 to $50,000 to do one foetal genome today.

But the cost and accuracy of DNA sequencing is improving at a blistering pace. The researchers estimated that the procedure could be widely available in three to five years. Others said it would take somewhat longer. It is already possible to determine the DNA sequence of a foetus by acquiring foetal cells through amniocentesis or chorionic villus sampling, which involves testing the placental tissue. But these procedures are invasive and carry a slight risk of inducing a miscarriage. For couples worried about passing on a genetic disease, it is also possible to use in vitro fertilization and have an embryo genetically tested before implantation into the womb.

But the technique described in the paper would not require complete cells from the foetus and would make such DNA testing easier, less risky and possible earlier in pregnancy than current techniques.

“If this sort of thing is ever to be used on a widespread basis, I think it necessarily has to be noninvasive," said Jay Shendure, associate professor of genome sciences at the University of Washington, who supervised the research team.

The genome was determined from blood samples taken 18.5 weeks into the pregnancy, although the researchers said the technique could probably be applied in the first trimester, as early as or even earlier than some invasive techniques.

The technique takes advantage of the discovery in the 1990s that fragments of DNA from the foetus can be found in a pregnant woman’s blood plasma, probably the result of foetal cells dying and breaking apart.

These fragments can be genetically analysed, providing that the foetal DNA fragments can be distinguished from the far more numerous fragments that come from the mother herself.

The analysis of foetal DNA fragments found in a pregnant woman’s blood is already used in new commercially available tests of the foetus’s gender, its paternity and whether it has Down syndrome. But reconstructing an entire genome from DNA fragments is much more difficult.

Such information would allow detection of so-called Mendelian disorders, such as cystic fibrosis, Tay-Sachs disease and Marfan syndrome, which are caused by mutations of a single letter in the genome.

More than 3,000 such diseases collectively occur in about 1% of births. The mutations can be inherited from the parents or they can arise spontaneously in the foetus.

Researchers led by Dennis Lo at the Chinese University of Hong Kong first showed in 2010 that reconstructing a foetal genome would be possible. Other work toward this goal has been done by Stephen Quake and colleagues at Stanford University.

But Lo’s team used a maternal sample obtained invasively. And it could determine only the inherited mutations, not the spontaneous ones.

The University of Washington researchers, with much of the work done by a graduate student, Jacob O. Kitzman, did not need an invasive test. And they were able to detect 39 of 44 such spontaneous mutations, though with a huge number of false positives.

“This will be a step towards having a better and better prenatal diagnosis that detects more and more at a reliable cost," said Arthur L. Beaudet, chairman of molecular and human genetics at Baylor College of Medicine in Houston.

©2012/the new york times

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