An Alu-mediated large deletion of the FUT2 gene in individuals with the ABO-Bombay phenotype
An Alu-mediated large deletion of the FUT2 gene in individuals with the ABO-Bombay phenotype
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DOI：
10.1007/s004390051013
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发表时间：
2000-01-01
期刊：
影响因子：
5.3
通讯作者：
Kimura, H
中科院分区：
文献类型：
--
作者：
Koda, Y;Soejima, M;Kimura, H
最近，我们在具有典型孟买ABO系统表型的个体中发现了分泌型α(1，2)岩藻糖基转移酶(FUT2)基因的等位基因缺失。FUT2基因由两个外显子组成，内含子由大约7kb的内含子隔开。第一个外显子是非编码的，而外显子2包含完整的编码序列。由于该缺失的5‘端断裂点已被定位到FUT2的单个内含子上，因此我们通过盒介导的聚合酶链式反应在孟买个体中克隆了该缺失的连接区。此外，从一个对照个体扩增了FUT2 3‘非翻译区到3’断裂点序列的区域。DNA序列分析表明，5‘端断裂点位于左侧游离Alu单体(flam-C)序列内，位于外显子1下游1.3kb，3’端断裂点位于完整的A12e元件(AluSx)内，位于外显子2下游1.5kb，缺失大小约为10kb。在5‘和3’断裂点周围的参考DNA序列之间存在25bp的序列同一性。这表明Alu介导的大基因缺失是印度孟买人分泌型α(1，3)岩藻糖基转移酶缺乏症的原因。
Recently, we have found an allelic deletion of the secretor alpha(1,2)fucosyltransferase (FUT2) gene in individuals with the classical Bombay phenotype of the ABO system. The FUT2 gene consists of two exons separated by an intron that spans approximately 7 kb. The first exon is noncoding, whereas exon 2 contains the complete coding sequence. Since the 5' breakpoint of the deletion has previously been mapped to the single intron of FUT2, we have cloned the junction region of the deletion in a Bombay individual by cassette-mediated polymerase chain reaction. In addition, the region from the 3' untranslated region of FUT2 to the 3' breakpoint sequence has been amplified from a control individual. DNA sequence analysis of this region indicates that the 5' breakpoint is within a free left Alu monomer (FLAM-C) sequence that lies 1.3 kb downstream of exon 1, and that the 3' breakpoint is within a complete A12e element (AluSx) that is positioned 1.5 kb downstream of exon 2. The size of the deletion is estimated to be about 10 kb. There is a 25-bp sequence identity between the reference DNA sequences surrounding the 5' and 3' breakpoints. This demonstrates that an Alu-mediated large gene deletion generated by unequal crossover is responsible for secretor alpha(1,3)fucosyltransferase deficiency in Indian Bombay individuals.