Scientists have successfully sequenced the genome of a baby in utero without tapping the amniotic sac, raising the possibility of a single non-invasive genetic screening for thousands of disorders during pregnancy.
A pregnant woman’s blood plasma contains cell-free DNA from her developing foetus and many labs are exploiting this phenomenon to develop non-invasive maternal blood tests to look at a foetus’ genetic make-up.
Researchers from the University of Washington have developed a method that uses a maternal blood sample at 18 weeks gestation, and a paternal saliva specimen to map the foetus’ DNA. They were able to pick out the parts of the baby’s genetic material inherited from each parent with over 98% accuracy. What sets their methods apart from other labs is that it can assess many and more subtle variations in the foetus’ genome – down to minute one-letter changes 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” said Jacob Kitzman, a National Science Foundation Graduate research Fellow.
The researchers – led by Kitzman and Matthew Snyder – checked the accuracy of their genetic predictions using umbilical cord blood collected at birth. They also repeated the method for another expectant couple closer to the start of their pregnancy.
However, Snyder says there is still more work to be done to improve the technique – children can have genetic variations not shared with either parent. These de novo mutations underpin a substantial proportion of dominant genetic disorders and searching for them is critical to comprehensive prenatal genetic diagnoses.
Ultradeep sequencing, computational biology and statistics could locate de novo mutations genome-wide in the growing foetus, and researchers discovered 39 of 44 mutations. They suggest a more refined, less costly version of their approach might make prenatal genetic screening vastly more comprehensive.
“This work opens up the possibility that we will be able to scan the whole genome of the foetus for more than 3,000 single-gene disorders through a single, non-invasive test,” said Dr Jay Shendure. “The capacity of genomics to generate data is outstripping our ability to interpret it in ways that are useful to physicians and patients. Although the non-invasive prediction of a foetal genome is now technically feasible, its interpretation – even for single-gene Mendelian disorders – will remain an enormous challenge.”