Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development
Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development
复制标题
DOI：
10.1093/hmg/ddg067
复制
发表时间：
2003-04-01
影响因子：
3.5
通讯作者：
Sadowski, P
中科院分区：
文献类型：
--
作者：
Weksberg, R;Smith, AC;Sadowski, P
Beckwith-Wiedemann综合征（BWS）的特征是体细胞过度生长和易患小儿胚胎性肿瘤。它与人类染色体11 p15上约1兆碱基的基因组区域内发现的一簇印记基因中的遗传或表观遗传异常有关。印记基因优先或排他地从父本或母本等位基因表达。11 p15区域被组织成两个印记域，其中基因组印记由单独的“印记控制区域”控制。25%至50%的BWS患者具有胰岛素样生长因子2（IGF 2）基因的双等位基因而非单等位基因表达。另有50%的患者存在表观遗传突变，导致称为KCNQ 1 OT 1的转录物印记丢失。这些基因中的每一个都位于两个印记域之一中，这两个印记域似乎在BWS中受到发育失调的影响。本文综述了BWS的研究对理解生长控制、肿瘤发生和基因组印记机制的重要意义。具体而言，甲基化和染色质修饰可以协调紧密连锁的印迹基因的表达。最后，我们讨论了如何与胚胎发生的早期阶段的表观遗传机制的知识，建议在目前的辩论中，围绕辅助生殖和克隆技术的谨慎。
The Beckwith-Wiedemann syndrome (BWS) is characterized by somatic overgrowth and a predisposition to pediatric embryonal tumors. It is associated with genetic or epigenetic abnormalities in a cluster of imprinted genes found within a genomic region of approximately one megabase on human chromosome 11p15. Imprinted genes are expressed preferentially or exclusively from either the paternal or maternal allele. The 11p15 region is organized into two imprinted domains in which genomic imprinting is controlled by separate 'imprinting control regions'. Twenty-five to 50% of BWS patients have biallelic rather than monoallelic expression of the insulin-like growth factor 2 (IGF2) gene. Another 50% of patients have an epigenetic mutation resulting in loss of imprinting of a transcript called KCNQ1OT1. Each of these genes resides in one of the two imprinted domains that appear to be subject to developmental dysregulation in BWS. In this review, we discuss the insights that the study of BWS have contributed to our understanding of the mechanisms of growth control, oncogenesis and genomic imprinting. Specifically, methylation and chromatin modification may coordinate the expression of closely linked imprinted genes. Finally, we discuss how knowledge of epigenetic mechanisms associated with the early stages of embryogenesis suggest caution in the current debate surrounding assisted reproductive and cloning technologies.