Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain.
Genome Res. 2013 Sep;23(9):1363-72. doi: 10.1101/gr.154187.112. Epub 2013 Aug 1.
DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation.
DNA 甲基化模式对于建立细胞、组织和生物体表型非常重要，但对于它们对自然人类变异的贡献知之甚少。为了确定它们对变异性的贡献，我们生成了三个人类群体（高加索裔美国人、非裔美国人和华裔美国人）的全基因组 DNA 甲基化图谱，并检查了差异甲基化的 CpG 位点。鉴定出的明显甲基化基因表明 DNA 甲基化对表型差异有影响，例如对某些疾病和病原体的易感性，以及对药物和环境因素的反应。DNA 甲基化差异可以部分追溯到遗传变异，表明差异甲基化的 CpG 位点在遗传密码和表型变异性之间起着进化确立的中介作用。值得注意的是，三分之一的 DNA 甲基化差异与任何遗传变异无关，这表明特定于人群的位点的变异发生在遗传和表观遗传水平上，突出了表观遗传修饰对自然人类变异的贡献。
