Open AccessSingle-molecule sequencing reveals a large population of long cell-free DNA molecules in maternal plasma
Author(s) -
Stephanie C Y Yu,
Peiyong Jiang,
Wenlei Peng,
Suk Hang Cheng,
Y T Tommy Cheung,
O Y Olivia Tse,
Huimin Shang,
Liona C. Poon,
Tak Yeung Leung,
K.C. Allen Chan,
Rossa W.K. Chiu,
Y.M. Dennis Lo
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2114937118
Subject(s) - dna , cell free fetal dna , cpg site , dna sequencing , biology , dna methylation , fetus , genetics , microbiology and biotechnology , gene , pregnancy , prenatal diagnosis , gene expression
Significance We revealed a large population of long cell-free DNA molecules (up to 23,635 bp in length) in maternal plasma and developed an approach which leveraged the abundance of CpG sites on long molecules to deduce the tissue of origin of individual plasma DNA molecules based on single-molecule methylation analysis. We illustrated how such an approach may be utilized to achieve noninvasive prenatal testing of monogenic diseases. We also revealed a reduction in amounts of such long cell-free DNA molecules and a different end motif profile in maternal plasma DNA from pregnancies with preeclampsia. Hence, long cell-free DNA molecules represent a valuable resource of biomarker development for pregnancy-associated disorders.