Fetal DNA Sequencing Opens Door

Fetal DNA obtained from the mother’s plasma can be used for whole-genome sequencing and identification of point mutations in the genome of the unborn child, Jay Shendure of the University of Washington, Seattle, and coworkers report (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3004323). Such noninvasive sequencing methods could be easier and safer than placental tissue sampling for the entire range of more than 3,000 known single-gene “Mendelian” disorders. The researchers determined a fetus genome sequence by combining individual genome sequencing of the two parents with 78-fold sequence coverage of the maternal plasma DNA, approximately 13% of which comes from the fetus. With this sequence information they predicted parental inheritance and identified point mutations—sequences not inherited from either parent—in the child’s DNA. They checked their findings by sequencing DNA obtained from cord blood after birth. The team correctly identified 39 of 44 point mutations, but with limited specificity (a measure related to false positives). In this case, they were better able to predict maternal than paternal inheritance because the father’s DNA, which was obtained from saliva, was of insufficient quality to identify haplotypes, which are combinations of gene variants located close to one another on a chromosome.