Center for Epigenetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Sci Transl Med. 2010 Sep 15;2(49):49ra67. doi: 10.1126/scitranslmed.3001262.
The epigenome consists of non-sequence-based modifications, such as DNA methylation, that are heritable during cell division and that may affect normal phenotypes and predisposition to disease. Here, we have performed an unbiased genome-scale analysis of ~4 million CpG sites in 74 individuals with comprehensive array-based relative methylation (CHARM) analysis. We found 227 regions that showed extreme interindividual variability [variably methylated regions (VMRs)] across the genome, which are enriched for developmental genes based on Gene Ontology analysis. Furthermore, half of these VMRs were stable within individuals over an average of 11 years, and these VMRs defined a personalized epigenomic signature. Four of these VMRs showed covariation with body mass index consistently at two study visits and were located in or near genes previously implicated in regulating body weight or diabetes. This work suggests an epigenetic strategy for identifying patients at risk of common disease.
表观基因组由非基于序列的修饰组成，例如 DNA 甲基化，这些修饰在细胞分裂过程中是可遗传的，可能会影响正常表型和疾病易感性。在这里，我们通过全面的基于阵列的相对甲基化（CHARM）分析，对 74 个人的约 400 万个 CpG 位点进行了无偏基因组规模分析。我们在整个基因组中发现了 227 个区域，这些区域在个体之间表现出极端的变异性（可变甲基化区域（VMRs）），基于基因本体论分析，这些区域富含发育基因。此外，这些 VMRs 中有一半在个体中平均 11 年内是稳定的，这些 VMRs 定义了个性化的表观基因组特征。其中四个 VMR 在两次研究访问中始终与体重指数呈共变，并且位于或靠近先前被认为调节体重或糖尿病的基因附近或附近。这项工作提出了一种基于表观遗传学的策略，用于识别患有常见疾病风险的患者。
