The fragmentation patterns of maternal plasma cell‐free DNA and its applications in non‐invasive prenatal testing

Abstract The discovery of cell‐free DNA (cfDNA) in maternal plasma has opened up new promises for the development of non‐invasive prenatal testing (NIPT). Application of cfDNA in NIPT of fetus diseases and abnormalities is restricted by the low amount of fetal DNA molecules in maternal plasma. Fetus‐derived cfDNA in maternal plasma are shorter than maternal DNA, thus leveraging the maternal and fetus‐derived cfDNA molecules size difference has become a novel and more accurate method for NIPT. However, multiple biological properties such as size distribution of plasma DNA, proportion of fetal‐derived DNA and methylation levels in maternal plasma across different gestational ages still remain largely unknown. Further insights into the size distribution and fragmentation pattern of circulating plasma cfDNA will shed light on the origin and fragmentation mechanisms of cfDNA during physiological and pathological processes in prenatal diseases and enhance our ability to take the advantage of plasma cfDNA as a molecular diagnostic tool. In the review, we start by summarizing the research techniques for the determination of the fragmentation profiles of cfDNA in maternal plasma. We then summarize the main progress and findings in size profiles of maternal plasma cfDNA and cffDNA. Finally, we discuss the potential diagnostic applications of plasma cfDNA size profiling.