Comparison of genomic and epigenomicexpression in monozygotic twins using next-generation sequencing.

受影响的单卵双胞胎之间疾病表现的不一致性归因于环境因素或X染色体失活（XCI）的不同模式。然而，最近的研究已经确定了单卵双胞胎之间的遗传和表观遗传差异，从而挑战了公认的区分先天和后天影响的实验模型。在这里，我们报告的基因组和表观基因组序列在皮肤成纤维细胞的不和谐的单卵双胞胎与Rett综合征，一个X连锁的神经发育障碍的特点是自闭症的功能，癫痫发作，步态共济失调和刻板的手部运动。在双胞胎中，在单核苷酸多态性（SNPs），插入-缺失多态性（indels）或拷贝数变异方面没有检测到可重复的差异。在涉及脑功能和骨骼组织的基因上游区域的成纤维细胞中检测到双胞胎之间DNA甲基化的差异，因此，DNA甲基化模式的差异可能是双胞胎之间Rett表型不一致的基础。

Discordance in disease manifestation between affected monozygotic twins has been attributed to either environmental factors or different patterns of X chromosome inactivation (XCI). However, recent studies have identified genetic and epigenetic differences between monozygotic twins, thereby challenging the accepted experimental model for distinguishing the effects of nature andnurture. Here, we report the genomic and epigenomic sequences in skin fibroblasts of a discordant monozygotic twin pair with Rett syndrome, an X-linked neurodevelopmental disorder characterized by autistic features, epileptic seizures, gait ataxia and stereotypical hand movements. In the twins, no reproducible differences were detected between the twins in single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (indels), or copy number variations. Differences in DNA methylation between the twins were detected in fibroblasts in the upstream regions of genes involved in brain function and skeletal tissues, and thus, the differences in DNA methylation patterns likely underlie the discordance in Rett phenotypes between the twins.