Selective Effect of DNA N6-Methyladenosine Modification on Transcriptional Genetic Variations in East Asian Samples

Genetic variations and DNA modification are two common dominant factors ubiquitous across the entire human genome and induce human disease, especially through static genetic variations in DNA or RNA that cause human genetic diseases. DNA N6-methyladenosine (6mA) methylation, as a new epigenetic modification mark, has been widely studied for regulatory biological processes in humans. However, the effect of DNA modification on dynamic transcriptional genetic variations from DNA to RNA has rarely been reported. Here, we identified DNA, RNA and transcriptional genetic variations from Illumina short-read sequencing data in East Asian samples (HX1 and AK1) and detected global DNA 6mA modification using single-molecule, real-time sequencing (SMRT) data. We decoded the effects of DNA 6mA modification on transcriptional genetic variations in East Asian samples and the results were extensively verified in the HeLa cell line. DNA 6mA modification had a stabilized distribution in the East Asian samples and the methylated genes were less likely to mutate than the non-methylated genes. For methylated genes, the 6mA density was positively correlated with the number of variations. DNA 6mA modification had a selective effect on transcriptional genetic variations from DNA to RNA, in which the dynamic transcriptional variations of heterozygous (0/1 to 0/1) and homozygous (1/1 to 1/1) were significantly affected by 6mA modification. The effect of DNA methylation on transcriptional genetic variations provides new insights into the influencing factors of DNA to RNA transcriptional regulation in the central doctrine of molecular biology.