Imprinting defects on human chromosome 15
Imprinting defects on human chromosome 15
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DOI：
10.1159/000090844
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发表时间：
2006-01-01
影响因子：
1.7
通讯作者：
Buiting, K
中科院分区：
文献类型：
--
作者：
Horsthemke, B;Buiting, K
普瑞德威利综合征 (PWS) 和安格曼综合征 (AS) 是两种不同的神经遗传疾病，是由人类 15 号染色体近端长臂上的印记基因功能丧失引起的。在少数 PWS 和 AS 患者中，这种疾病是由于印记异常和基因沉默造成的。在患有 PWS 和印记缺陷的患者中，父本染色体带有母本印记。在患有 AS 和印记缺陷的患者中，母体染色体带有父系印记。压印缺陷提供了一个独特的机会来识别压印擦除、重置和维护中涉及的一些因素和机制。在大约 10% 的情况下，印记缺陷是由影响 SNURF-SNRPN 基因座 5' 端的微缺失引起的。这些缺失定义了 15q 印记中心 (IC)，它调节整个域的印记。这些发现已在基因敲除小鼠和转基因小鼠中得到证实和扩展。在大多数有印记缺陷的患者中，不正确的印记是在没有 DNA 序列变化的情况下出现的，这可能是由于印记过程的随机错误或外源因素的影响。
The Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct neurogenetic diseases that are caused by the loss of function of imprinted genes on the proximal long arm of human chromosome 15. In a few percent of patients with PWS and AS, the disease is due to aberrant imprinting and gene silencing. In patients with PWS and an imprinting defect, the paternal chromosome carries a maternal imprint. In patients with AS and an imprinting defect, the maternal chromosome carries a paternal imprint. Imprinting defects offer a unique opportunity to identify some of the factors and mechanisms involved in imprint era- sure, resetting and maintenance. In approximately 10% of cases the imprinting defects are caused by a microdeletion affecting the 5 ' end of the SNURF-SNRPN locus. These deletions define the 15q imprinting center (IC), which regulates imprinting in the whole domain. These findings have been confirmed and extended in knock-out and transgenic mice. In the majority of patients with an imprinting defect, the incorrect imprint has arisen without a DNA sequence change, possibly as the result of stochastic errors of the imprinting process or the effect of exogenous factors.