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. 1991 Nov;49(5):1055–1062.

Recombinational biases in the rearranged C1-inhibitor genes of hereditary angioedema patients

Dominique Stoppa-Lyonnet, Christiane Duponchel, Tommaso Meo, Jérôme Laurent, Philip E Carter, Mario Arala-Chaves, Jacques H M Cohen, Georg Dewald, Joelle Goetz, Georges Hauptmann, Gilbert Lagrue, Philippe Lesavre, Margarita Lopez-Trascasa, Gabriella Misiano, Claude Moraine, Alain Sobel, Pierre J Späth, Mario Tosi
PMCID: PMC1683256  PMID: 1656734

Abstract

DNA structural changes responsible for hereditary angioedema were sought in the C1-inhibitor gene, which contains unusually dense clusters of Alu repeats in various orientations. Among patients belonging to 45 unrelated families, eight partial C1-inhibitor gene deletions and a partial duplication were found. Four deletions had one of the boundaries within the gene and the other in extragenic regions–in three cases 5' of the gene and in one case 3' of the gene. The boundaries of the partial duplication and of the remaining four deletions mapped instead within a few kilobases of exon 4. The same element–Alu 1 –the first of three tandem Alu repeats preceding exon 4, contained one of the breakpoints of each of these five rearrangements. Moreover, these recombination breakpoints spread over the entire length of Alu 1, in contrast with the tight clustering observed near the 5' end of Alu sequences rearranged in other human genes. Thus, two uncommon recombinational biases are observed in the Alu rearrangements of hereditary angioedema patients; one promotes the occurrence of intragenic breakpoints in a single Alu repeat, and the other allows the breaks to be distributed over the entire Alu structure rather than within the hot spot of the left Alu monomer. A region of potential Z-DNA structure, located 1.7 kb upstream of Alu 1, may contribute to both peculiarities.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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