This study demonstrates a noninvasive method for diagnosing fetal aneuploidy using shotgun sequencing of cell-free DNA from maternal plasma. The researchers sequenced cell-free DNA from 18 pregnant women, obtaining an average of 5 million sequence tags per sample. They found that the over- and underrepresentation of chromosomes in the maternal plasma DNA can be used to detect fetal aneuploidy, such as trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), and trisomy 13 (Patau syndrome). The method is polymorphism-independent and can be applied to arbitrarily small fractions of fetal DNA. The study also characterized the characteristics of cell-free plasma DNA, finding evidence that it is enriched for sequences from nucleosomes. The results suggest that this approach could be a universal, noninvasive diagnostic test for fetal aneuploidy, providing a minimally invasive alternative to traditional invasive procedures.This study demonstrates a noninvasive method for diagnosing fetal aneuploidy using shotgun sequencing of cell-free DNA from maternal plasma. The researchers sequenced cell-free DNA from 18 pregnant women, obtaining an average of 5 million sequence tags per sample. They found that the over- and underrepresentation of chromosomes in the maternal plasma DNA can be used to detect fetal aneuploidy, such as trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), and trisomy 13 (Patau syndrome). The method is polymorphism-independent and can be applied to arbitrarily small fractions of fetal DNA. The study also characterized the characteristics of cell-free plasma DNA, finding evidence that it is enriched for sequences from nucleosomes. The results suggest that this approach could be a universal, noninvasive diagnostic test for fetal aneuploidy, providing a minimally invasive alternative to traditional invasive procedures.