Researchers at Tel Aviv University say they have developed a new, noninvasive method of discovering genetic disorders that can let parents find out the health of their fetus as early as 11 weeks into pregnancy.
A simple blood test lets doctors diagnose genetic disorders in fetuses early in pregnancy by sequencing small amounts of DNA in the mother’s and the father’s blood. A computer algorithm developed by the researchers analyzes the results of the sequencing and then produces a “map” of the fetal genome, predicting mutations with 99 percent or better accuracy, depending on the mutation type, the researchers said in a study published Wednesday in Genome Research.
The algorithm is able to distinguish between the genetic material of the parents and that of the fetus, said Prof. Noam Shomron of Tel Aviv University’s Sackler School of Medicine led the research, in a phone interview with The Times of Israel.
White blood cells in the blood sample contain only the DNA of the mother, Shomron explained, while the plasma contains the DNA of both the mother and the fetus. The algorithm thus uses the white blood cells as a reference, to be able to distinguish the DNA of the mother from that of the fetus.
There are some 7,000 genes in the human genome that have specific mutations that can cause genetic diseases, some of which have “serious implications” for the health of the fetus, said Shomron in a statement.
“These diseases are called monogenic diseases, because they are caused by a defect in one specific gene. Known examples are Tay-Sachs and CF (cystic fibrosis),” he said.
Most monogenic diseases are very rare, he said, but even so, there are thousands of mutations that can represent “a significant risk for the birth of a baby that is sick.”
Tests generally performed today to determine chromosomal abnormalities in the fetus are invasive, such as amniocentesis, a medical procedure in which amniotic fluid is extracted from the womb with a syringe. They also carry a small risk of miscarriage.
Newly developed noninvasive prenatal diagnosis (NIPD) for chromosome disorders such as Down syndrome have gained traction as an effective way to detect inherited diseases early in pregnancy.
Existing noninvasive procedures “are only able to see major changes in the DNA,” Shomron said. For example, “the genetic mechanism behind Down syndrome affects a very large portion of the genome and therefore is easier to detect.”
He said that his team of Tel Aviv researchers “upgraded” this noninvasive fetal genotyping “to detect many other diseases that are caused by smaller parts of the genome.
“This is like looking at a map of the world and noticing not only that a continent is missing, but also that a single house is missing. We see even the smallest changes. We offer a huge-fold better resolution,” he said.
The study was conducted by Tel Aviv University graduate student Tom Rabinowitz with Avital Polsky, Artem Danilevsky, Guy Shapira and Chen Raff, from Prof. Shomron’s lab. The study is a 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.
The findings are “important to reduce the risk in current prenatal tests,” Shomron said. The new procedure “bears only a minimal risk for the mother and fetus compared with such invasive techniques as the amniotic fluid test. We will now be able to identify numerous mutations and diseases in a safe and simple procedure available at the doctor’s office.”
“The practical applications are endless,” he added, with a single blood test that would be able to detect a wide range of genetic diseases.
Shomron and his colleagues tested blood samples from three families at Rabin Medical Center in the 11th week of gestation. They extracted maternal and paternal DNA from their white blood cells and fetal DNA from a placental cell sample. They also extracted circulating cell-free fetal DNA from the maternal blood.
“We sequenced all these DNA samples and created a computer algorithm that utilizes the parental DNA as well as the cell-free fetal DNA to reconstruct the fetal genome and predict mutations,” said Shomron. “We compared our predictions to the true fetal DNA originating from the placenta. Our model is the first to predict small inherited insertions and deletions. The method described can serve as a general framework for noninvasive prenatal diagnoses.”
The researchers are working on further improving the accuracy of the method and extending it to detect even more types of mutations, the university said in a statement.