ADENOSINE-DEAMINASE (ADA) DEFICIENCY DUE TO DELETION OF THE ADA GENE PROMOTER AND 1ST EXON BY HOMOLOGOUS RECOMBINATION BETWEEN 2 ALU ELEMENTS
ADENOSINE-DEAMINASE (ADA) DEFICIENCY DUE TO DELETION OF THE ADA GENE PROMOTER AND 1ST EXON BY HOMOLOGOUS RECOMBINATION BETWEEN 2 ALU ELEMENTS
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DOI：
10.1172/jci113458
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发表时间：
1988-05-01
影响因子：
15.9
通讯作者：
KAUFMAN, RE
中科院分区：
文献类型：
--
作者：
MARKERT, ML;HUTTON, JJ;KAUFMAN, RE
在15-20%患有严重联合免疫缺陷（SCID）的儿童中，潜在的缺陷是腺苷脱氨酶（ADA）缺乏。本研究的目的是确定ADA缺乏性SCID患者的精确分子缺陷，我们之前已经证明该患者完全缺乏ADA mRNA和ADA基因的结构改变。通过详细的Southern分析，我们现在已经确定结构变化是.apprx的缺失。3.3 kb，其中包括ADA基因的外显子1和启动子区域。DNA序列分析表明，该缺失通过在缺失侧的两个现有Alu重复序列之间的同源重组产生了一个新的完整的Alu重复序列。Alu序列的26 bp重组接头包括与RNA聚合酶III启动子同源的10 bp“B”序列。这是Alu重复序列中涉及B序列的同源重组的第一个例子。类似的重组事件已被发现涉及Alu重复序列，其中重组关节位于聚合酶III分裂启动子的A和B序列之间。这些事件的非随机位置表明这些片段可能是重组的热点。
In 15-20% of children with severe combined immunodeficiency (SCID), the underlying defect is adenosine deaminase (ADA) deficiency. The goal of this study was to determine the precise molecular defect in a patient with ADA-deficient SCID whom we previously have shown to have a total absence of ADA mRNA and a structural alteration of the ADA gene. By detailed Southern analysis, we now have determined that the structural alteration is a deletion of .apprx. 3.3 kb, which included exon 1 and the promoter region of the ADA gene. DNA sequence analysis demonstrates that the deletion created a novel, complete Alu repeat by homologous recombination between two existing Alu repeats that flanked the deletion. The 26-bp recombination joint in the Alu sequence includes the 10-bp "B" sequence homologous to the RNA polymerase III promoter. This is the first example of homologous recombination involving the B sequence in Alu repeats. Similar recombination events have been identified involving Alu repeats in which the recombination joint was located between the A and B sequences of the polymerase III split promoter. The nonrandom location of these events suggests that these segments may be hot spots for recombination.