Israelis Invent Risk-free, High-resolution Test for Fetal Mutations in First Trimester

Current tests such as amniocentesis are less accurate and can only be done much later in the pregnancy ■ University working on commercialization

Ruth Schuster
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FILE PHOTO: An expecting mother is examined by a midwife during a home visit in Free Union, Virgina, United States, November 29, 2005.
FILE PHOTO: An expecting mother is examined by a midwife during a home visit in Free Union, Virgina, United States, November 29, 2005.Credit: Andrew Shurtleff / AP
Ruth Schuster

Researchers at Tel Aviv University have developed a blood test to check a fetus for genetic problems in the first trimester, at infinitely greater resolution than existing techniques, and at zero risk to the mother or baby, they reported Wednesday in Genome Research journal.

The university is still working on commercialization of the blood test, but Prof. Noam Shomron of TAU’s Sackler School of Medicine is confident that one day, their breakthrough test will replace amniocentesis and microvilli testing, procedures done later in pregnancy that pose risks to either the mother or fetus.

For now the lab has proven its technology on samples from pregnancies as early as weeks 10 to 12, while amniocentesis for instance is typically done from the 14th week to the 20th.

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Why did the university focus on weeks 10 to 12? “Just because that’s the samples we received,” Shomron told Haaretz. “We are trying to reduce this timeline to day 40.”

That is not a random aspiration. In Jewish practice, fetal termination is permissible until the 40th day of pregnancy, but existing technologies for genertic testing are much too late for that.

Amnio and microvilli testing are relatively crude tools that can detect abnormalities at the level of the chromosome – a missing section, for instance, involving millions upon millions of nucleotides.

“From amniocentesis, you could tell if an arm from chromosome 19 moved to another chromosome, for instance,” Shomron says. “Our method can find a single point mutation, a single change of nucleotide. It has far better resolution.”

Shomron, who led the research by TAU graduate students Tom Rabinowitz, Avital Polsky, Artem Danilevsky, Guy Shapira and Chen Raff, helpfully provides an analogy.

“Amniocentesis looks at chromosomes or parts of chromosomes to see if they are duplicated or not. It’s like looking at Planet Earth from outer space and asking if there’s another continent,” he says. Amnio can tell you if the baby has Down’s syndrome because that is caused by the presence of all or part of a third copy of chromosome 21 – which, in cellular terms, is huge. “We look at specific point mutations. It’s like looking at Planet Earth and finding a particular house in a particular street.”

The method involves taking tissue samples from both mother and father, and sequencing them.

Technically, the DNA from daddy can come from a cheek swab or “any tissue he’s willing to give,” and it’s just a reference point. Also technically, the DNA from mother could also come from her cheek or anywhere else, but blood is better. Why is that? Because her blood plasm has bits of that baby’s DNA in it too. That way they can obtain the mother’s pure DNA (from white blood cells – red blood cells don’t have DNA), and then obtain the baby’s DNA from the blood plasma.

“Our algorithm can tell whether the tiny pieces of DNA in the blood came from the mom or the fetus,” Shomron explains. And one needs the daddy DNA because they can subtract mother and father genomes from the equation and remain with information that is pure baby.

The norm has become to undergo genetic testing before getting pregnant, certainly in Israel, where certain populations have heightened propensity for genetic diseases, such as Tay Sachs among Ashkenazis and broad bean allergy among those of Middle—Eastern descent. Usually the tests cover about 30 common mutations.

But there are thousands upon thousands of detrimental, extremely rare mutations. This simple blood test, says Shomron, can scan for thousands of extremely rare but disabling mutations, and help the parents plan ahead. Knowing the father’s DNA can not only help track down the source of a mutation, but help to calculate its recessivity or dominance.

The team believes that its algorithm, used on the sequencing results, will predict mutations in the fetus with 99% or better accuracy, depending on the mutation type. “The practical applications are endless: a single blood test that would detect a wide range of genetic diseases, such as Tay-Sachs disease, cystic fibrosis and many others,”

DNA chips, the latest wrinkle in fetal testing, are also much cruder in output than the future blood test.

Asked about the future, Shomron explains that the technique was developed in the TAU lab and the university is working on commercializing it, transferring the technology to private companies.

The work was done in collaboration with Dr. David Golan of the Technion-Israel Institute of Technology, and Prof. Lina Basel-Salmon and Dr. Reut Tomashov-Matar of Rabin Medical Center.