Noninvasive fetal genomic, methylomic, and transcriptomic analyses using maternal plasma and clinical implications

•Fetal DNA and RNA are present in the plasma of pregnant women.•These molecules may be used for noninvasive prenatal testing (NIPT).•Fetal chromosomal aneuploidies and monogenic disorders can be detected using NIPT.•Fetal genomes, methylomes, and transcriptomes have been sequenced noninvasively.

The discovery of cell-free fetal DNA in maternal plasma opened up new possibilities for noninvasive prenatal testing (NIPT). Conceptual advances in single-molecule counting have resulted in robust methods for the NIPT of fetal chromosomal aneuploidies and subchromosomal aberrations. Such methods are employed worldwide and are among the most rapidly adopted genomic tests. Furthermore, approaches for fetal whole-genome sequencing from maternal plasma, as well as for targeted detection of many single-gene disorders, have been reported. Recently, fetal methylome and transcriptome sequencing from maternal plasma have also been achieved, potentially allowing fetal physiological and pathological processes to be monitored noninvasively using maternal blood. These advances herald exciting future applications in prenatal medicine.