A deletion involving Alu sequences in the beta-hexosaminidase alpha-chain gene of French Canadians with Tay-Sachs disease - PubMed (original) (raw)
. 1987 Nov 15;262(32):15396-9.
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- PMID: 2824459
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A deletion involving Alu sequences in the beta-hexosaminidase alpha-chain gene of French Canadians with Tay-Sachs disease
R Myerowitz et al. J Biol Chem. 1987.
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Abstract
French Canadians living in eastern Quebec are carriers of a severe type of Tay-Sachs disease, known as the classic form, 10 times more often than the general population. The alpha-chain of beta-hexosaminidase A, a lysosomal enzyme composed of two chains (alpha, beta), bears the mutation in this inherited disorder. We previously reported that the 5' end of the alpha-chain gene was deleted in two such patients (Myerowitz, R., and Hogikyan, N.D. (1986) Science, 232, 1646-1648). The present study reports the size, precise location, and environment of the deletion. A clone encompassing the deletion was isolated from a genomic library constructed in lambda EMBL3 with DNA from a patient's fibroblasts. Comparison of the restriction maps of the clone with that of the normal gene (Proia, R.L., and Soravia, E. (1987) J. Biol. Chem. 262, 5677-5681) showed that the deletion was 7.6 kilobases long and included part of intron 1, all of exon 1 and extended 2000 base pairs upstream past the putative promotor region of the alpha-chain gene. These data are consistent with the inability to detect mRNA and immunoprecipitable alpha-chain protein in this mutant. Sequence analysis of the deletion junction in the mutant and corresponding regions of the normal gene demonstrated the presence of similarly oriented Alu sequences at the 5' and 3' deletion boundaries. The data are in accord with the possibility that the deletion may have arisen during homologous recombination from unequal crossing over between Alu sequences.
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