Maternal Plasma Bisulfite DNA Sequencing: Tomorrow Starts Today

Abstract

The advent of genomics holds great promise for the study of human biology and clinical diagnostics, making it possible to move from hypothesis-driven studies of candidate gene studies to hypothesis-generating, data-driven genomewide scans (1). The report in this issue of Clinical Chemistry by Lun, Chiu, and coworkers of the Centre for Research into Circulating Fetal Nucleic Acids at the Chinese University of Hong Kong is an excellent example of this process (2). The investigators used genomewide bisulfite DNA sequencing of maternal plasma to comprehensively assess the epigenomic profiles of both fetal and maternal epigenomes noninvasively, serially, and on a genomewide scale. As a proof of principle, the authors correctly detected trisomy 21 by assessing the methylation density of chromosome 21 and correctly deduced the imprinting status of 4 selected loci: H19 2 [H19, imprinted maternally expressed transcript (non-protein coding)], KCNQ1OT1 [KCNQ1 opposite strand/antisense transcript 1 (non-protein coding)], MEST (mesoderm specific transcript), and GNAS (GNAS complex locus). This report makes you eager to explore roads previously less traveled or considered dead ends, roads that now appear to be going someplace interesting. The routes include developing applications with both short- and long-term impacts and addressing important questions related to various disciplines. The following examples illustrate this process. ### PRESYMPTOMATIC MONITORING OF FETAL WELL-BEING Of the approximately 2 million loci for which the mother was homozygous, Lun, Chiu, and coworkers found that DNA sequencing of maternal plasma demonstrated the presence of a nonmaternal (i.e., fetal) allele in about 5.5% of cases. These fetal-specific reads covered 218 …