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.
CITATION STYLE
Chatterton, Z., Mendelev, N., Chen, S., Carr, W., Kamimori, G. H., Ge, Y., … Haghighi, F. (2021). Bisulfite Amplicon Sequencing Can Detect Glia and Neuron Cell-Free DNA in Blood Plasma. Frontiers in Molecular Neuroscience, 14. https://doi.org/10.3389/fnmol.2021.672614
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