During pregnancy, more than a tenth of the free-floating DNA present in the mother’s blood originates from the fetus. Many studies have previously explored the possibility of sequencing this free-floating DNA to detect damaging genetic variations in developing children. However, prior methods have only been able to determine the presence of more detectable disorders such as trisomy 21. Recently, a team of investigators led by Jay Shendure of the Department of Genome Sciences at the University of Washington developed a new, more informative method for sequencing the genomes of fetuses.
The team’s procedure reconstructs the fetus’ entire genetic code, down to single nucleotides, by synthesizing the available genetic information from mother, father, and child. For one expecting family, the group sequenced the entire maternal and paternal genomes as well as the free-floating DNA within the mother’s blood. They also determined the mother’s haplotypes, the statistically predictable groupings of genetic variation. Using all of this information, the group modeled patterns of inheritance and predicted the genome of the fetus. Following birth, the child’s genome was sequenced, and it was revealed that the group’s extrapolated genome was over 98 percent accurate.
Traditional prenatal DNA testing for fetuses requires tapping the uterus for sample, a process that can cause miscarriage in rare cases. The newer, noninvasive approaches, including the one developed by Shendure’s team, rely on free-floating DNA and do not pose this risk.
Making available the entire genome of the developing child, the Shendure team’s method is also the most comprehensive proven method of prenatal DNA testing. In theory, the level of resolution provided will allow doctors to see every genetic abnormality, even de novo mutations, which exist in neither parent but are unique to the offspring. The availability of this information will better fulfill the purpose of prenatal DNA testing: helping expecting parents to make better decisions about their child’s health care.
Despite its advantages, the novel technique still requires development. Most notably, the data it generates, an entire human genome, is not yet completely practical in analysis. Certainly, the presence of well-understood disorders such as cystic fibrosis, phenylketonuria, and Tay-Sachs disease can be deduced from the data. However, the vast majority of the human genome is not yet understood. Numerous genome-wide association studies that correlate genetic variations with human characteristics, ranging from susceptibility to heart disease to intelligence, are adding to our understanding. With additional advancements in genomics and biostatistics, the technique’s full potential can be realized. As DNA sequencing rapidly becomes more affordable, the technique will also become more accessible. Before long, the technique Shendure and his colleagues developed will be able to provide invaluable information to expecting parents while minimizing risk to the unborn child.
Cover Image: DNA microarrays are a newer technology that allows visualization of single nucleotide polymorphisms. Each colored spot on the shown chip corresponds to a single nucleotide variation in the human genome. Fetal cells can be invasively extracted, and their DNA can be studied using a microarray to determine genetic abnormalities. Courtesy of James Madison University.