Frontiers in Molecular Neuroscience (Jul 2021)

Bisulfite Amplicon Sequencing Can Detect Glia and Neuron Cell-Free DNA in Blood Plasma

  • Zac Chatterton,
  • Zac Chatterton,
  • Zac Chatterton,
  • Zac Chatterton,
  • Zac Chatterton,
  • Natalia Mendelev,
  • Natalia Mendelev,
  • Natalia Mendelev,
  • Natalia Mendelev,
  • Sean Chen,
  • Sean Chen,
  • Sean Chen,
  • Sean Chen,
  • Walter Carr,
  • Walter Carr,
  • Gary H. Kamimori,
  • Yongchao Ge,
  • Andrew J. Dwork,
  • Andrew J. Dwork,
  • Andrew J. Dwork,
  • Fatemeh Haghighi,
  • Fatemeh Haghighi,
  • Fatemeh Haghighi,
  • Fatemeh Haghighi

DOI
https://doi.org/10.3389/fnmol.2021.672614
Journal volume & issue
Vol. 14

Abstract

Read online

Sampling the live brain is difficult and dangerous, and withdrawing cerebrospinal fluid is uncomfortable and frightening to the subject, so new sources of real-time analysis are constantly sought. Cell-free DNA (cfDNA) derived from glia and neurons offers the potential for wide-ranging neurological disease diagnosis and monitoring. However, new laboratory and bioinformatic strategies are needed. DNA methylation patterns on individual cfDNA fragments can be used to ascribe their cell-of-origin. Here we describe bisulfite sequencing assays and bioinformatic processing methods to identify cfDNA derived from glia and neurons. In proof-of-concept experiments, we describe the presence of both glia- and neuron-cfDNA in the blood plasma of human subjects following mild trauma. This detection of glia- and neuron-cfDNA represents a significant step forward in the translation of liquid biopsies for neurological diseases.

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