Size-tagged preferred ends in maternal plasma DNA shed light on the production mechanism and show utility in noninvasive prenatal testing

Proceedings of the National Academy of Sciences of the United States of America
Kun SunY M Lo

Abstract

Cell-free DNA in human plasma is nonrandomly fragmented and reflects genomewide nucleosomal organization. Previous studies had demonstrated tissue-specific preferred end sites in plasma DNA of pregnant women. In this study, we performed integrative analysis of preferred end sites with the size characteristics of plasma DNA fragments. We mined the preferred end sites in short and long plasma DNA molecules separately and found that these "size-tagged" ends showed improved accuracy in fetal DNA fraction estimation and enhanced noninvasive fetal trisomy 21 testing. Further analysis revealed that the fetal and maternal preferred ends were generated from different locations within the nucleosomal structure. Hence, fetal DNA was frequently cut within the nucleosome core while maternal DNA was mostly cut within the linker region. We further demonstrated that the nucleosome accessibility in placental cells was higher than that for white blood cells, which might explain the difference in the cutting positions and the shortness of fetal DNA in maternal plasma. Interestingly, short and long size-tagged ends were also observable in the plasma of nonpregnant healthy subjects and demonstrated size differences similar to those in the pregnant ...Continue Reading

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Citations

Oct 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Peiyong JiangRossa W K Chiu
Jan 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sarah T K SinY M Dennis Lo
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Aug 18, 2020·Genome Research·Peiyong JiangY M Dennis Lo
Sep 3, 2020·Open Biology·Alexis ZukowskiSrinivas Ramachandran
Dec 30, 2018·Proceedings of the National Academy of Sciences of the United States of America·Lee SerpasY M Dennis Lo
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Aug 20, 2020··Ľubica JanovičováBarbora Vlková

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Methods Mentioned

BETA
size profiling
PCR

Software Mentioned

SOAP2

Related Concepts