KDDI Research Inc., Ohara 2-1-15, Fujimino, Saitama, 356-0003, Japan.
Research and Development Section, Anicom Specialty Medical Institute Inc., Kanagawa, Japan.
BMC Genomics. 2024 Nov 15;25(1):1089. doi: 10.1186/s12864-024-10963-2.
DNA methylation is a covalent bond modification that is observed mainly at cytosine bases in the context of CG pairs. DNA methylation patterns reflect the status of individual tissues, such as cell composition, age, and the local environment, in mammals. Genetic factors also impact DNA methylation, and the genetic diversity among various dog breeds provides a valuable platform for exploring this topic. Compared to those in the human genome, studies on the profiling of methylation in the dog genome have been less comprehensive.
Our study provides extensive profiling of DNA methylation in the whole blood of three dog breeds using whole-genome bisulfite sequencing. The difference in DNA methylation between breeds was moderate after removing CpGs overlapping with potential genetic variation. However, variance in methylation between individuals was common and often occurred in promoters and CpG islands (CGIs). Moreover, we adopted contextual awareness methodology to characterize DNA primary sequences using natural language processing (NLP). This method could be used to effectively separate unmethylated CGIs from highly methylated CGIs in the sequences that are identified by the conventional criteria.
This study presents a comprehensive DNA methylation landscape in the dog blood. Our observations reveal the similar methylation patterns across dog breeds, while CGI regions showed high variations in DNA methylation level between individuals. Our study also highlights the potential of NLP approach for analyzing low-complexity DNA sequences, such as CGIs.
DNA 甲基化是一种主要发生在 CG 对中胞嘧啶碱基上的共价键修饰。在哺乳动物中,DNA 甲基化模式反映了个体组织的状态,如细胞组成、年龄和局部环境。遗传因素也会影响 DNA 甲基化,而不同犬种之间的遗传多样性为探索这一课题提供了宝贵的平台。与人类基因组相比,犬基因组甲基化分析的研究还不够全面。
本研究采用全基因组亚硫酸氢盐测序技术,对三种犬种的全血进行了广泛的 DNA 甲基化谱分析。在去除与潜在遗传变异重叠的 CpG 后,品种间 DNA 甲基化的差异适中。然而,个体间的甲基化差异很常见,通常发生在启动子和 CpG 岛(CGI)中。此外,我们采用了自然语言处理(NLP)的上下文感知方法来对 DNA 一级序列进行特征描述。该方法可用于有效分离传统标准识别的序列中非甲基化的 CGI 和高度甲基化的 CGI。
本研究描绘了犬血液中的全面 DNA 甲基化图谱。我们的观察结果表明,不同犬种之间的甲基化模式相似,而 CGI 区域的个体间 DNA 甲基化水平存在高度差异。我们的研究还强调了 NLP 方法在分析低复杂度 DNA 序列(如 CGI)方面的潜力。