Sizing Up Cell-Free DNA

In 1947, Mandel and Metais discovered the unusual phenomenon of circulating cell-free DNA (1). Although one might naively think that DNA is found only in the nuclei of cells, it turns out that a substantial amount of small DNA fragments circulates within the blood. These molecules are not part of intact cells but are the detritus of dead and apoptosed cells that have spilled their guts into the blood. Their genomes are chewed up into little pieces, the presence of which can be measured like any other blood analyte. Although great effort has been expended to try to understand how the relative concentrations of these DNA species may correlate with health, their greatest value has been to measure the proportion of foreign genomes within an individual. In certain cases that is quite straightforward: Cancer-related mutations can be used to some extent to determine the progress of disease (2), male chromosomal markers can be used for prenatal sex determination (3), and, in a similar fashion, women who have received organ transplants from males can be monitored for the amount of organ-specific DNA (4, 5).The cell-free DNA phenomenon might have …