Genomic organization of the X-linked gene (PIG-A) that is mutated in paroxysmal nocturnal haemoglobinuria and of a related autosomal pseudogene mapped to 12q21.
Genomic organization of the X-linked gene (PIG-A) that is mutated in paroxysmal nocturnal haemoglobinuria and of a related autosomal pseudogene mapped to 12q21.
复制标题
在阵发性睡眠性血红蛋白尿症中突变的 X 连锁基因 (PIG-A) 和映射到 12q21 的相关常染色体假基因的基因组组织。
作者：
M. Bessler;P. Hillmen;L. Longo;L. Luzzatto;P. Mason
最近发现，PIG-A基因在所有阵发性睡眠性血红蛋白尿症(PNH)病例中都存在缺陷，其产物参与了糖磷脂酰肌醇(GPI)锚点合成的早期步骤之一。通过从人噬菌体文库中分离基因组克隆，我们现在发现PIG-A基因由六个外显子(第一个是非编码的)组成，横跨17kb的DNA，我们已经将该基因定位到染色体位置Xp22.1。PIG-A启动子具有看家基因的特征。我们还分离了与PIG-A基因交叉杂交的克隆，从而鉴定了一个无内含子PIG-A假基因(psi PIG-A)，并将其定位在染色体位置12q21。PSI PIG-A不能起作用，因为它包含几个终止密码子和一个移码。这些数据使得设计扩增整个PIG-A编码区的引物成为可能，而不包括psi PIG-A序列，这将有助于PNH患者PIG-A突变的表征。数据库搜索显示，PIG-A与许多糖基转移酶具有同源性，并且与酵母SPT14基因编码的蛋白质高度同源(45%)。
The PIG-A gene, whose product is involved in one of the early steps in the synthesis of glycan phosphatidylinositol (GPI) anchors, has been recently found to be defective in all cases of paroxysmal nocturnal haemoglobinuria (PNH). By isolating genomic clones from a human phage library we now show that the PIG-A gene consists of six exons (the first of which is non-coding) spanning 17 kb of DNA, and we have mapped the gene to chromosomal position Xp22.1. The PIG-A promoter has features of a housekeeping gene. We have also isolated additional clones which cross-hybridize to PIG-A cDNA, and we have thus identified an intronless PIG-A pseudogene (psi PIG-A), which we have mapped to chromosomal position 12q21. psi PIG-A cannot be functional because it contains several stop codons and a frameshift. These data make it possible to design primers for amplification of the entire PIG-A coding region, with exclusion of psi PIG-A sequences, which will facilitate characterization of PIG-A mutations in patients with PNH. Database searches revealed that PIG-A contains homologies with a number of glycosyl transferases and is highly homologous (45%) to the protein encoded by the yeast SPT14 gene.