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

受影响的同卵双胞胎之间的疾病表现不一致被归因于环境因素或不同的X染色体失活(XCI)模式。然而，最近的研究发现了同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自然和后天影响的实验模型。在这里，我们报道了一对患有Rett综合征的不协调同卵双胞胎的皮肤成纤维细胞的基因组和表观基因组序列。Rett综合征是一种X连锁的神经发育障碍，以自闭症、癫痫发作、步态共济失调和典型的手运动为特征。在双胞胎中，在单核苷酸多态(SNPs)、插入-缺失多态(INDELs)或拷贝数变异方面，双胞胎之间没有检测到可重复的差异。双胞胎之间DNA甲基化的差异是在涉及大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的，因此，DNA甲基化模式的差异可能是双胞胎之间Rett表型不一致的原因。

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.