The Impact of DNA Methylation Dynamics on the Mutation Rate During Human Germline Development

In this study, we used whole genome bisulfite sequencing (WGBS) data of cells at 13 stages of human germline development and rare variants from the 1000 Genome Project as proxies for germline mutations to investigate the correlation between dynamic methylation levels and germline mutation rates at different scales. At the single-site level, we found a significant correlation between methylation and the germline point mutation rate at CpG sites during germline developmental stages. Then we explored the mutability of methylation dynamics in all stages. Our results also showed a broad correlation between the regional methylation level and the rate of C > T mutation at CpG sites in all genomic regions, especially in intronic regions; a similar link was also seen at all chromosomal levels. Our findings indicate that the dynamic DNA methylome during human germline development has a broader mutational impact than is commonly assumed.

Source: G3: Genes Genomes Genetics - September 1, 2020 Category: Genetics & Stem Cells Authors: Zhou, Y., He, F., Pu, W., Gu, X., Wang, J., Su, Z. Tags: Investigations Source Type: research