-- Paper Maekawa et al. is a different insertion some nucleotide differences (from OMIM) Acholinesterasemia; Muratani et al. (1991) described inactivation of the cholinesterase gene by an Alu insertion. The patient was a 60-year-old Japanese man who was by chance found to have no cholinesterase activity in his serum when he was hospitalized for diabetes mellitus. By using BCHE cDNA as a probe, Muratani et al. (1991) isolated clones from a genomic library constructed from the patient's DNA. Sequencing showed that exon 2 of the BCHE gene was disrupted by a 342-bp Alu insertion. The Alu element included a poly(A) tract of 38 bp and showed 93% sequence homology with a current type of human Alu consensus sequence. The subject was homozygous and the Alu insertion was inherited in his family. It was flanked by 15 bp of target site duplication in exon 2 corresponding to positions 1062-1076 of the cDNA, indicating that the Alu element could have been integrated by retrotransposition.
The human cholinesterase (ChE) gene from a patient with acholinesterasemia was cloned and analyzed. By using ChE cDNA as a probe, four independent clones were isolated from a genomic library constructed from the patient's DNA. Sequencing analysis of all of the four clones revealed that exon 2 of the ChE gene was disrupted by a 342-base-pair (bp) insertion of Alu element, including a poly(A) tract of 38 bp, which showed 93% sequence homology with a current type of human Alu consensus sequence. Southern blot analysis showed that the Alu insertion occurred in both alleles of the patient and was inherited in the patient's family. This Alu insertion was flanked by 15-bp of target site duplication in exon 2 corresponding to positions 1062-1076 of ChE cDNA, indicating that an Alu element could have been integrated by retrotransposition. Thus, this case provides an important clue to the mechanism of inactivation of a gene by integration of a retrotransposon.