Identification of novel imprinted transcripts in the Prader-Willi syndrome and Angelman syndrome deletion region: Further evidence for regional imprinting control
Identification of novel imprinted transcripts in the Prader-Willi syndrome and Angelman syndrome deletion region: Further evidence for regional imprinting control
复制标题
DOI：
10.1086/302817
复制
发表时间：
2000-03-01
影响因子：
9.8
通讯作者：
Wevrick, R
中科院分区：
文献类型：
--
作者：
Lee, S;Wevrick, R
人类染色体15q11-q13的缺失和其他异常与两种发育障碍有关，即Prader-Willi综合征(PWS)和Angelman综合征(AS)。印记的、父系表达的基因的表达缺失与PWS有关。然而，导致PWS的印记基因的数量，以及印记信号以亲本特有的方式使基因的一个副本沉默的范围尚不清楚。为了识别其他可能影响PWS表型的印记基因，并了解15q11-q13中印记的区域控制，我们构建了PWS-AS缺失区间的印记转录图谱。用逆转录-聚合酶链式反应(RT-PCR)检测来自辐射杂交人类转录图或物理图的22个表达序列标签的印迹状态，并与转录本在物理图上的位置相关。七个新的父系表达的转录本定位于一个类似于Snrpn相关印记中心周围的1.5-Mb结构域，该中心已经包括四个印记的父系表达基因。在缺失区的所有其他测试的新转录本都来自这两个等位基因。围绕印记中心的排他性父系表达区域暗示了印记过程的强大区域控制。这项研究为进一步研究引起或改变与15q11-q13重排相关的表型的其他基因提供了手段。
Deletions and other abnormalities of human chromosome 15q11-q13 are associated with two developmental disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Loss of expression of imprinted, paternally expressed genes has been implicated in PWS. However, the number of imprinted genes that contribute to PWS, and the range over which the imprinting signal acts to silence one copy of the gene in a parent-of-origin-specific manner, are unknown. To identify additional imprinted genes that could contribute to the PWS phenotype and to understand the regional control of imprinting in 15q11-q13, we have constructed an imprinted transcript map of the PWS-AS deletion interval. The imprinting status of 22 expressed sequence tags derived from the radiation-hybrid human transcript maps or physical maps was determined in a reverse transcriptase-PCR assay and correlated with the position of the transcripts on the physical map. Seven new paternally expressed transcripts localize to an similar to 1.5-Mb domain surrounding the SNRPN-associated imprinting center, which already includes four imprinted, paternally expressed genes. All other tested new transcripts in the deletion region were expressed from both alleles. A domain of exclusive paternal expression surrounding the imprinting center suggests strong regional control of the imprinting process. This study provides the means for further investigation of additional genes that cause or modify the phenotypes associated with rearrangements of 15q11-q13.