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Cell-Free DNA Integrity Analysis in Urine Samples
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High-resolution analysis for urinary DNA jagged ends.

Tingting Xie1,2,3, Guangya Wang1,2,3, Spencer C Ding1,2,3

  • 1Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.

NPJ Genomic Medicine
|February 24, 2022
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Summary
This summary is machine-generated.

Urinary DNA harbors longer jagged ends than plasma DNA. This study refined jagged end sequencing (Jag-seq) to reveal 10-nt periodicities in urinary DNA, which may indicate cancer and histone interactions.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Biochemistry

Background:

  • Single-stranded DNA ends, termed jagged ends, are more prevalent in urinary DNA than plasma DNA.
  • Previous jagged end sequencing (Jag-seq) methods lacked resolution for precise length determination in urinary DNA due to reliance on CpG methylation analysis.

Purpose of the Study:

  • To develop a high-resolution Jag-seq method for precise urinary DNA jagged end length determination.
  • To investigate the characteristics and potential biological significance of urinary DNA jagged ends.

Main Methods:

  • Developed a high-resolution Jag-seq technique utilizing methylation at non-CpG cytosine sites.
  • Analyzed jagged end lengths and distributions in urinary DNA and plasma DNA.
  • Investigated the impact of renal cell carcinoma and heparin treatment on jagged end patterns.
  • Examined the relationship between urinary DNA jagged ends and nucleosomal structures.

Main Results:

  • Urinary DNA exhibited significantly longer jagged ends (~26-nt) compared to plasma DNA (~17-nt).
  • Distinct 10-nt periodicities were observed in urinary DNA jagged end length distribution, less prominent in plasma DNA.
  • The amplitude of these 10-nt periodicities increased in renal cell carcinoma patients.
  • Heparin treatment reduced the observed 10-nt periodicities in urinary DNA.
  • Urinary DNA jagged ends frequently extended into nucleosomal cores, suggesting histone interactions.

Conclusions:

  • High-resolution Jag-seq enables precise characterization of urinary DNA jagged ends.
  • Urinary DNA jagged ends possess unique length distributions and periodicities, potentially linked to disease states like renal cell carcinoma.
  • These findings suggest novel insights into DNA fragmentation, histone interactions, and potential biomarkers in urine DNA.