Advanced Analysis of Human Plasma Circulating DNA Sequences Produced by Parallel Tagged Sequencing on the 454 Platform

The structure of human plasma circulating nucleic acids is currently extensively studied for an acquisition and extension of fundamental knowledge on DNA and RNA functions inside cells as well as between cells – in extracellular fluids of both humans and animals. Previously, we reported data on the general analysis of DNA sequences from plasma of 10 healthy individuals and 12 prostate cancer patients. In order to further characterize this array of sequences we performed comparative analysis of chromosome distribution, repeat content and epigenetic characteristics of plasma DNA. It was found that Long terminal repeats (LTR) [Endogenous retrovirus-related (ERVL) and Mammalian apparent LTR-retrotransposon (MaLR)] DNA were elevated in plasma of healthy individuals while repeats of other classes were at the same or lowered frequency compared to random genome DNA. Satellite repeats attributed to chromosome 12 were elevated in plasma of prostate cancer patients. Epigenome and chromatin structure attributes of circulating DNA emphasized an elevated frequency of histone H3 containing the dimethylated lysine 27 (H3K27me2) associated DNA. The elevated frequency of LTR repeats in circulating human DNA can implicate the possibility of a hypothetical active DNA release mechanism in human cells, and histone H3K27me2 may be involved in this process.