Baby’s genome deciphered prenatally from parents’ lab tests

Scientists have successfully sequenced the genome of a baby in the womb without tapping its protective fluid sac. Maternal blood sampled at about 18 weeks into the pregnancy and a paternal saliva specimen contained enough information for the scientists to map the foetus’ DNA. This method was later repeated for another expectant couple closer to the start of their pregnancy. The researchers checked the accuracy of their genetic predictions using umbilical cord blood collected at birth.
Jacob Kitzman and Matthew Snyder, working in the laboratory of Dr. Jay Shendure, associate professor of genome sciences at the University of Washington, led the study. Kitzman is a National Science Foundation Graduate Research Fellow.
Scientists have long known that a pregnant woman’s blood plasma contains cell-free DNA from her developing foetus. Foetal DNA appears in the mother’s plasma a few weeks after conception. It rises during gestation and normally vanishes after the baby arrives. While the concentration varies among individuals, about 10 percent of the cell-free DNA in a pregnant woman’s blood plasma comes from her foetus.
Based on this phenomenon, other research labs are designing maternal blood tests for major aberrations in the foetus’s genetic makeup. The tests are considered a safer substitute for the more invasive sampling of fluid from the uterus, a common procedure in obstetrical practice. These new tests search for just a few genetic disorders or specific congenital abnormalities. For example, a test targeted for Down syndrome would look for evidence of three copies of chromosome 21.
Kitzman explained what distinguishes his team’s latest methods is the ability to assess many and more subtle variations in the foetus’ 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,’ said Kitzman.
With technical advances as well as statistical modelling, the research group overcame several obstacles that had stymied previous efforts to determine foetal genomes. With a preponderance of maternal rather than foetal DNA in plasma samples, a major problem was figuring out which genetic variants had passed from mother to child. The scientists applied a recently developed technique to resolve the mother’s haplotypes, which are groups of genetic variations residing on the same chromosome. From these groupings, the researchers could pick out the parts of the baby’s genetic material inherited from each parent with over 98 percent accuracy.
‘It was rewarding to apply biostatistics to help solve this problem,’ said Snyder, who came to genome sciences from the fields of statistics and economics.
Still, he added, there is more work to be done to improve this technique. The researchers pointed to the need for a more robust, scalable, overarching protocol, as well as ways to lower costs and automate and standardise parts of the process. Washington University