Plagge A, Kelsey G
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Cytogenet Genome Res. 2006;113(1-4):178-87. doi: 10.1159/000090830.
Gnas is an enigmatic and rather complex imprinted gene locus. A single transcription unit encodes three, and possibly more, distinct proteins. These are determined by overlapping transcripts from alternative promoters with different patterns of imprinting. The canonical Gnas transcript codes for Gsalpha, a highly conserved signalling protein and an essential intermediate in growth, differentiation and homeostatic pathways. Monoallelic expression of Gnas is highly tissue-restricted. The alternative transcripts encode XLalphas, an unusual variant of Gsalpha, and the chromogranin-like protein Nesp55. These transcripts are expressed specifically from the paternal and maternal chromosomes, respectively. Their existence in the Gnas locus might imply functional connections amongst them or with Gsalpha. In this review, we consider how imprinting of Gnas was discovered, the phenotypic consequences of mutations in each of the gene products, both in the mouse and human, and provide some conjectures to explain why this elaborate imprinted locus has evolved in this manner in mammals.
Gnas是一个神秘且相当复杂的印记基因座。一个单一的转录单元编码三种，甚至可能更多不同的蛋白质。这些蛋白质由来自具有不同印记模式的替代启动子的重叠转录本决定。典型的Gnas转录本编码Gsα，一种高度保守的信号蛋白，是生长、分化和稳态途径中的重要中间体。Gnas的单等位基因表达具有高度的组织限制性。替代转录本编码XLαs，一种Gsα的异常变体，以及嗜铬粒蛋白样蛋白Nesp55。这些转录本分别从父本和母本染色体特异性表达。它们在Gnas基因座中的存在可能意味着它们之间或与Gsα存在功能联系。在这篇综述中，我们探讨了Gnas印记是如何被发现的，小鼠和人类中每种基因产物突变的表型后果，并提供了一些推测来解释为什么这个复杂的印记基因座在哺乳动物中以这种方式进化。
