Identification of CpG Site SNPs Potentially Subject to Epigenetic Control via DNA Methylation

DNA methylation is a key epigenetic regulator of gene expression in many cellular processes. Several studies have shown associations between methylation and transcription patterns. However, the association between genetic variation and DNA methylation patterns is not yet clear. Genetic variation in CpG dinucleotides can either create or disrupt opportunity for cytosine methylation and, thus, potentially change methylation patterns. The introduction or removal of CpG sites that are potentially DNA methylation sites, has been suggested as a mechanism by which single nucleotide polymorphisms (SNPs) can affect gene function genome-wide via epigenetic modifications (meSNPs). Using the variant annotations for SNPs identified in Run5 of the 1000 bull genomes project and the UMD3.1 bovine reference genome sequence assembly, we identified and classified 12,836,763 meSNPs according to the pattern of variation caused at the CpG site. We have also analyzed the genomic distribution of the meSNPs, with the majority being located in intergenic regions (68.10%) and then in introns (26.36%). The remaining meSNPs are distributed throughout the coding region of genes (1.27%), approximately 0.29% in UTRs, a small number localized to non-coding RNAs (0.11%), and 3.93% fell within proximal promoters. Overall, meSNPs represent 22.53% of 56,969,697 SNPs described in the database of which 11.26% are located in CpG islands. These annotations are important for determining potential associations of meSNPs with phenotypes via methylation profiles and expression levels of target genes in cattle.

Acknowledgments: São Paulo Research Foundation (FAPESP) #2015/20557-5 and #2016/07584-6