Genetic Screening Shows Promise During Pregnancy

The whole genome sequence of a human fetus has been reconstructed by analyzing blood samples from the mother and saliva samples from the father.

The new noninvasive technique could help screen for different types of genetic mutations in the fetus, include disorders such as cystic fibrosis, Huntington's disease, and Tay-Sachs disease, without increasing the risk of miscarriage.

Scientists at the University of Washington (Seattle, WA, USA) have opened up the possibility of assessing a fetus noninvasively for all single-gene disorders. Although fetal DNA is found in the mother's blood plasma, it can be challenging to distinguish which genetic signature belongs to the fetus and which belongs to the mother. As a result, the team used a new technique in order to identify blocks of genetic variation known as haplotypes, which could be traced back to the mother's genome.

To test the accuracy of their genetic predictions, the team collected blood from the baby's umbilical cord at birth and found that they had identified 39 of the baby's 44 new mutations during the genome reconstruction. Together with data from the father's saliva sample, they were able to determine which genomes the fetus inherited. At 18.5 weeks gestation, the scientists were able to map the whole genome of a fetus and then reconstructed it using DNA from parental samples.

Genomic DNA was extracted from whole blood with the Gentra Puregene Kit (Qiagen, Valencia, CA, USA), or from saliva, with the Oragene Dx (DNA Genotek; Kanata, ON, Canada). Purified DNA was fragmented by sonication with a Covaris S2 instrument (Woburn, MA, USA). Indexed shotgun sequencing libraries were prepared with the KAPA Library Preparation Kit (Kapa Biosystems; Woburn, MA, USA) and all libraries were sequenced on HiSeq 2000 instruments (Illumina; San Diego, CA, USA).

The techniques used by the team were able to evaluate many and more subtle variations in the fetus' genome, down to tiny, "one-letter" changes in the DNA code. Jay Shendure, MD, PhD, the lead author of the study said, "This work opens up the possibility that we will be able to scan the whole genome of the fetus for more than 3,000 single-gene disorders through a single, noninvasive test." The study was published in the June 2012 issue of the journal Science Translational Medicine.

Related Links:
University of Washington
Qiagen
DNA Genotek