CpG Island Definition and Methylation Mapping of the T2T-YAO Genome

Abstract

Precise definition of every primary methylation sites and their secondary structural feature – CpG islands – are pivotal for subsequent genome-wide epigenetic studies of Chinese populations under different physiological and pathological conditions while the reference genome T2T-YAO is ready for use timely. We first align and examine the two high-quality genome references T2T-YAO and T2T-CHM13 from different ethnic backgrounds in a base-by-base fashion, computing their density-defined and position-defined CGIs. Second, we not only map some representative genome-wide methylation data of selective organs onto the T2T-YAO and T2T-CHM13 genomes but also scrutinize the difference of between these epigenetic parameters. Our major findings are: (1) There is about 4.7% (4.665%–5.751%) sequence difference between the two genomes, and the divergent sequences and related genes are closely correlated to neurological functions. (2) CGIs associated with the divergent sequences are statistically significantly different with respect to CpG density and O/E values. (3) Not only whole-genome-bisulfite-sequencing or WGBS data for T2T-YAO have greater coverage of CpG sites as compared to those of T2T-CHM13, but also T2T-YAO shows more hyper-methylated CpG sites than T2T-CHM13 does.