Baby’s Genome Deciphered Prenatally from Parents’ Lab Tests

They were able to sequence a baby's genome prenatally and noninvasively with about 98% accuracy

Maternal blood sampled at about 18 weeks into the pregnancy and a paternal saliva specimen contained enough information for the scientists to map the fetus’ DNA. This method was later repeated for another expectant couple closer to the start of their pregnancy. The scientists checked the accuracy of their genetic predictions using umbilical cord blood collected at birth.

Fetal 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% of the cell-free DNA in a pregnant woman’s blood plasma comes from her fetus.

Jacob Kitzman and Matthew Snyder, working in the laboratory of Prof. Jay Shendure, associate professor of genome sciences at the University of Washington (Seattle, WA, USA) led the study.

Other research labs are designing maternal blood tests for major aberrations in the fetus’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.

Dr. Kitzman explained what distinguishes his team’s latest methods is the ability to assess many and 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,” said Kitzman.

A child can have genetic variations not shared with either parent. These de novo mutations can occur during egg or sperm formation, at, or near conception. Because de novo mutations underpin a substantial proportion of dominant genetic disorders, searching for them is critical to comprehensive prenatal genetic diagnosis. The scientists showed that ultradeep sequencing, computational biology and statistics could locate de novo mutations genome-wide in the growing fetus. They discovered 39 of the baby’s 44 de novo mutations while it was a fetus.

The results suggest that a more refined, less costly version of their approach might make prenatal genetic screening vastly more comprehensive. Although technical and analytical difficulties currently exist, the investigators anticipate removal of these hindrances.

Prof. Shendure mentioned recent advances in detection of de novo mutations, which have underscored the important role they play in disorders with more complex origins. These include, but are not limited to, some cases of autism, epilepsy, schizophrenia, or intellectual impairments. However, using genome sequencing to predict and communicate risk to patients would be hard in a clinical setting, due to limited knowledge about multigene diseases and their many contributing factors beyond genetics.

This noninvasive approach to obtaining the fetal genome is reported in the June 6, 2012, issue of Science Translational Medicine, a journal of the American Association for the Advancement of Science.

Related Links:
Genome Sciences at the University of Washington
American Association for the Advancement of Science