Scientists map genome of fetus with non-invasive test

Scientists have successfully sequenced the entire genome of a human fetus using a blood sample from the mother and a saliva sample from the father, according to a study published Wednesday.

The non-invasive test could lead down the road to a “vastly comprehensive” prenatal genetic screening that could scan for more than 3000 Mendelian disorders, such as Down syndrome, Huntington’s disease, and cystic fibrosis, the study researchers said.

“This opens up the possibility of prenatally diagnosing a much broader range of genetic conditions,” researcher Dr. Jay Shendure, associate professor of genome sciences at the University of Washington, told  “There are roughly 3000 Mendelian disorders for which we understand the genetic basis. Each of the diseases is incredibly rare, but collectively they account for one percent of new births.”

In addition, by sequencing very deeply, the researchers were able to detect ‘de novo’ or brand new mutations in the fetus that were not present in the mother or father.  De novo mutations are the basis of a substantial proportion of genetic disorders, such as autism spectrum disorders and epilepsy, making it critical to search for them as part of a comprehensive screening, the researchers said.

The test was conducted 18 weeks into couples’ pregnancies, and proved to be approximately 98 percent accurate in predicting Mendelian disorders.  It also detected 39 of a baby’s 44 de novo mutations.

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“Papers a few years ago from different groups showed this could be possible, but they lacked the haplotype [genetic] technology,” Shendure said.

The researchers said new developments in technology allowed them to assess more subtle variations in the fetus’ genome, down to “a minute, one letter change in the DNA code.”

“The improved resolution is like going from being able to see that two books are stuck together to being able to notice one word misspelled on a page,” study co-leader Jacob Kitzman, a National Science Foundation Graduate Research Fellow, said in a statement.

Currently, doctors use invasive testing such as amniocentesis or chorionic villus sampling, in which a needle takes tissue from the womb, to test for certain genetic disorders.  The tests are associated with certain risks – even increased chances of fetal loss.

“There are many instances where women have invasive testing for a specific genetic disorder,” Shendure said, “but there could be a single non-invasive test that encompasses all of those scenarios.  Most women would opt for the non-invasive test, I think.”

Shendure added the test would need to be refined – and researchers would need to learn how to better interpret the vast amount of genetic data – before this type of screening could be available to the public.

The study was published in the journal Science Translational Medicine.