Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.
Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.
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人类伽马重链疾病。
DOI：
10.1172/jci113722
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Buxbaum,J
中科院分区：
文献类型：
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作者：
Alexander,A;Anicito,I;Buxbaum,J
从一个人淋巴样细胞系中分离到一个基因组克隆，该细胞系合成了一种NH2末端缺失的伽马3重链疾病蛋白。核苷酸序列分析表明，从310bp5‘到启动子ATG，通过VH氨基酸14的密码子序列是正常的。氨基酸15来源于最后一个J4氨基酸的密码子。因此，该克隆包含除氨基酸14以外的VH区的密码子缺失，以及整个D区和大部分J编码区的密码子缺失。在缺失后的400bp处观察到一些序列异常。除此之外，与已发表的J和插入序列有很好的同源性，包括那些包含增强子元件的序列。1200个碱基的开关区被对应于CH1的3‘三分之一的序列突然中断。因此，第二次缺失消除了CH1 5‘端的受体剪接位点。当发生初级RNA转录本的剪接时，截短的VH区通过J4供体剪接位点连接到下一个可用的受体位点5‘，连接到第一铰链外显子。因此，异常的血清蛋白是两次缺失和剪接纠正以及合成后的NH2末端蛋白降解的产物。
A genomic clone was isolated from a human lymphoid cell line which synthesized an NH2-terminally deleted gamma 3 heavy chain disease protein. Nucleotide sequence analysis revealed a normal sequence from 310 bp 5' to the initiator ATG through the codon for VH amino acid 14. Amino acid 15 was derived from the codon for the last J4 amino acid. Thus, the clone contained a deletion of the codons for the VH region beyond amino acid 14, as well as those for the entire D region and most of the J coding region. Some sequence abnormalities were observed in the 400 bp after the deletion. Beyond this, there was excellent homology to published J and intervening sequences, including those containing the enhancer elements. The 1,200-bp switch region was abruptly interrupted by a sequence corresponding to the 3' one-third of CH1. Thus, a second deletion eliminated the acceptor splice site at the 5' end of CH1. When splicing of the primary RNA transcript occurred, the truncated VH region was joined via the J4 donor splice site to the next available acceptor site 5' to the first hinge exon. Hence, the aberrant serum protein was the product of two deletions and a splice correction as well as postsynthetic NH2-terminal proteolysis.Images