Haruta Masayuki, Meguro Makiko, Sakamoto Yu-Ki, Hoshiya Hidetoshi, Kashiwagi Akiko, Kaneko Yasuhiko, Mitsuya Kohzoh, Oshimura Mitsuo
Division of Molecular and Cell Genetics, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan.
Division of Cancer Diagnosis, Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan.
J Hum Genet. 2005;50(3):124-132. doi: 10.1007/s10038-005-0231-2. Epub 2005 Mar 3.
Human chromosome 15q11-q13 involves a striking imprinted gene cluster of more than 2 Mb that is concomitant with multiple neurological disorders manifested by Prader-Willi syndrome (PWS) and Angelman syndrome (AS). PWS and AS patients with imprinting mutation have microdeletions, which share a 4.3 kb short region of overlap (SRO) at the 5' end of the paternal SNURF-SNRPN gene in PWS, or on the maternal allele, which shares a 880 bp SRO located at the 35 kb upstream of the SNURF-SNRPN promoter in AS. Recent studies have revealed an essential role of PWS-SRO in the postzygotic maintenance of the appropriate epigenotype on the paternal chromosome. For AS-SRO, however, there is insufficient experimental evidence exists to determine the direct functions. Here we show that the complete deletion of AS-SRO does not cause any anomalies of imprinted gene expression or DNA methylation on the mutated human chromosome 15, further supporting the idea that AS-SRO is dispensable for post implantation imprint maintenance. This implies that AS-SRO is not essential for the robust epigenotype preservation in somatic cells.
人类染色体15q11 - q13包含一个超过2 Mb的显著印记基因簇，该基因簇与普拉德 - 威利综合征（PWS）和安吉尔曼综合征（AS）所表现出的多种神经疾病相关。患有印记突变的PWS和AS患者存在微缺失，在PWS中，这些微缺失在父本SNURF - SNRPN基因5'端共享一个4.3 kb的短重叠区域（SRO），而在AS中，微缺失发生在母本等位基因上，该等位基因在SNURF - SNRPN启动子上游35 kb处共享一个880 bp的SRO。最近的研究表明，PWS - SRO在父本染色体上合子后适当表观基因型的维持中起着至关重要的作用。然而，对于AS - SRO，尚无足够的实验证据来确定其直接功能。在此我们表明，AS - SRO的完全缺失不会导致突变的人类染色体15上印记基因表达或DNA甲基化出现任何异常，这进一步支持了AS - SRO对于植入后印记维持是可有可无的这一观点。这意味着AS - SRO对于体细胞中强大的表观基因型保存并非必不可少。
