Identification of a novel paternally expressed gene in the Prader-Willi syndrome region.
Identification of a novel paternally expressed gene in the Prader-Willi syndrome region.
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普瑞德-威利综合征区域一个新的父系表达基因的鉴定。
DOI：
10.1093/hmg/3.10.1877
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发表时间：
1994
影响因子：
3.5
通讯作者：
Francke,U
中科院分区：
文献类型：
--
作者：
Wevrick,R;Kerns,JA;Francke,U
我们从Prader - Willi综合征（PWS）近端人类染色体15q缺失重叠最小区域分离出一个新基因。采用直接选择法分离prader - willi综合征区印迹基因（IPW），并在缺失区植入人工染色体。ipwi是拼接和聚腺苷化的，但其最长的开放阅读框仅编码45个氨基酸，这表明它的功能与RNA类似，类似于h19和xist。该RNA在成人和胎儿组织中广泛表达，并在人类细胞的细胞质部分中发现，这也是H19非翻译RNA的情况，但与主要在细胞核中发现的XIST RNA不同。利用序列多态性，证实父本等位基因在淋巴母细胞和成纤维细胞中独占表达；在胎儿组织中发现单等位基因表达。ipwi位于snrpn的远端约150kb处，snrpn是缺失间隔中唯一已知的另一个基因，并且位于易位断点的近端约50kb处，该易位断点定义了PWS区域的远端和Angelman综合征（AS）区域的近端。与snrpn的情况一样，15q11 - q13缺失的PWS患者不表达sipw，而在Angelman综合征患者中表达正常。缺乏表达可能直接导致PWS表型。或者，fipwmrna产物可能在印迹过程中发挥作用，作用于位于PWS区域近端或AS区域远端的基因。
We have isolated a novel gene from the Prader - Willi syndrome (PWS) smallest region of deletion overlap in proximal human chromosome 15q.IPW(Imprinted gene in thePrader-Willi syndrome region) was isolated using the direct selection method and yeast artificial chromosomes localized to the deletion region.IPWis spliced and polyadenylated but its longest open reading frame codes for only 45 amino acids, suggesting that it functions as an RNA, similar toH19andXIST. The RNA is widely expressed in adult and fetal tissues and is found in the cytoplasmic fraction of human cells, which is also the case for the H19 non-translated RNA, but differs from the XIST RNA which is found predominantly in the nucleus. Using a sequence polymorphism, exclusive expression from the paternal allele in lymphoblasts and fibroblasts was demonstrated; monoallelic expression was found in fetal tissues.IPWis located about 150 kb distal toSNRPN, the only other known gene in the deletion interval, and about 50 kb proximal to the breakpoint of a translocation which defines the distal end of the PWS region and the proximal end of the Angelman syndrome (AS) region. As is the case withSNRPN, PWS patients with 15q11 – q13 deletions do not expressIPW, where as expression is normal in Angelman syndrome patients. Lack of expression ofIPWmay contribute to the PWS phenotype directly. Alternatively, the mRNA product ofIPWmay play a role in the imprinting process, acting either on genes located proximally in the PWS region or distally in the AS region.