Genomic organization of human DLG4, the gene encoding postsynaptic density 95.
Genomic organization of human DLG4, the gene encoding postsynaptic density 95.
复制标题
人类 DLG4 的基因组结构，编码突触后密度 95 的基因。
DOI：
10.1046/j.1471-4159.1999.0732250.x
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发表时间：
1999
影响因子：
4.7
通讯作者：
Forsman-Semb,K
中科院分区：
文献类型：
--
作者：
Stathakis,DG;Udar,N;Sandgren,O;Andreasson,S;Bryant,PJ;Small,K;Forsman-Semb,K
摘要：我们确定了DLG4的外显子-内含子组织并表征了DLG4的5'侧翼启动子区域。 DLG4 位点包含约 30 kb，由 22 个外显子组成，大小范围为 28 至 1,218 个核苷酸。除内含子5的剪接受体位点是TG而不是AG外，所有剪接位点均符合GT-AG规则。发现 DLG4 的三个不同外显子在组织子集中交替剪接。其中两个变异会导致突触后密度 95 (PSD95) 同工型发生改变，从而显着截断蛋白质。第三个剪接变体代表外显子 4 的延伸，编码额外的 33 个氨基酸片段。对DLG4核心启动子区域的分析表明，该基因的表达是由一个无TATA的启动子控制的，使用嵌入CpG岛内的单个转录起始位点。DLG4映射到染色体17p13.1上的一个区域，已知该区域包含常染色体显性视锥细胞营养不良5的基因座。在15名视锥细胞营养不良患者中进行了DLG4编码区和剪接位点突变的扫描，其中包括来自5个家庭的先证者，显示与DLG4区域的连接。在任何患者中均未发现致病突变，这表明 DLG4 不是这种遗传性眼病的致病基因。
Abstract: We have determined the exon‐intron organization and characterized the 5′‐flanking promoter region ofDLG4. Encompassing ~30 kb, theDLG4locus is composed of 22 exons that range in size from 28 to 1,218 nucleotides. All splice sites conform to the GT‐AG rule, except for the splice acceptor site of intron 5, which is TG instead of AG. Three different exons ofDLG4were found to be alternatively spliced in a subset of tissues. Two of these variants result in altered postsynaptic density 95 (PSD95) isoforms that dramatically truncate the protein. The third splicing variant represents an extension of exon 4 that encodes an additional 33‐amino acid segment. Analysis of the core promoter region forDLG4suggests that the expression of this gene is controlled by a TATA‐less promoter using a single transcriptional start site embedded within a CpG island.DLG4maps to a region on chromosome 17p13.1 known to contain a locus for autosomal dominant cone dystrophy 5. Scanning for mutations in theDLG4coding region and splice sites was performed in 15 cone dystrophy patients, including probands from five families showing linkage to theDLG4region. No disease‐causing mutations were identified in any patients, suggesting thatDLG4is not the causative gene for this genetic eye disorder.