DNTP develops whole-genome sequencing of cell-free DNA in blood
Researchers from the Division of the National Toxicology Program have developed a protocol for whole-genome sequencing of low quantities of circulating cell-free DNA. Small amounts of DNA are typically released into blood as byproducts of programmed cell death. Increased levels of circulating cell-free DNA have been associated with environmental stressors and various diseases, including cancer and autoimmune disorders.
Whole-genome sequencing of circulating cell-free DNA could be used for discovering biomarkers or genomic variants associated with diseases. But it has been challenging to detect sequence variants at the whole-genome level due to the limited quantity of circulating cell-free DNA. As a result, few studies have applied whole-genome sequencing to clinical blood samples of cell-free DNA.
The researchers reported procedures for extracting and amplifying low amounts of circulating cell-free DNA, sequencing the whole genome, and analyzing genomic alterations. They applied this approach to cell-free DNA in one-milliliter blood samples obtained from two healthy human donors. This reliable, high-quality method could extend the utility of circulating cell-free DNA for a wide range of research and clinical purposes.
According to the authors, future work is required to refine the technique for clinical studies. Ultimately, whole-genome sequencing of circulating cell-free DNA may hold promise for disease diagnosis, staging, and therapeutic decisions. (JW)
Citation: Foley JF, Elgart B, Alex Merrick B, Phadke DP, Cook ME, Malphurs JA, Solomon GG, Shah RR, Fessler MB, Miller FW, Gerrish KE. 2021. Whole genome sequencing of low input circulating cell-free DNA obtained from normal human subjects. Physiol Rep 9(15):e14993.