Widespread RNA and DNA Sequence Differences in the Human Genome

The transmission of information from DNA to RNA is a critical process. It is assumed that DNA is faithfully copied into RNA. However, when we compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals, we uncovered more than 20,000 sites where the RNA sequences do not match that of the DNA. Validations using RNA sequences from another laboratory and re-sequencing of the DNA and RNA samples confirmed these findings. All 12 possible categories of discordances were found, with A-to-G and C-to-U being the most common. About 50% of the differences involved conversions between purines and pyrimidines. These differences were non-random as many sites were found in multiple individuals. The same differences were also found in primary skin cells in a separate set of 20 individuals. In addition, when these differences were found, they were seen in nearly all transcripts. Thus, these widespread RNA-DNA differences in the human genome provide a yet unexplored aspect of genome variation that affect gene expression and therefore phenotypic and disease manifestations. identification of RNA and DNA differences For alignment of the short reads sequences to the human transcriptome(Gencode NCBI36 version 3c), we used the program BOWTIE (version 0.12.7). ***This submission represents the RNA-seq component of the study