Refining Noninvasive Prenatal Diagnosis with Single-Molecule Next-Generation Sequencing

The gradual elimination of risky procedures used to sample fetal material for prenatal diagnosis has been an important objective in medicine. It is often stated that more fetuses are lost due to such invasive procedures (amniocentesis and chorionic villus sampling) than are identified as carrying a chromosomal abnormality. Noninvasive prenatal diagnosis (NIPD) 2 has developed substantially since the discovery in 1997 that appreciable amounts of free fetal DNA occur in maternal plasma (1). This discovery rapidly paved the way for the detection of paternally inherited alleles in maternal blood, including, most notably, Rh D blood group, fetal sex, and single-gene disorders. For more than a decade now, NIPD has been used routinely for pregnancies in which paternally inherited alleles require detection because their inheritance would indicate a …