Journal Article

High Level of Unequal Meiotic Crossovers at the Origin of the 22q11.2 and 7q11.23 Deletions

Alessandra Baumer, Fabrizio Dutly, Damina Balmer, Mariluce Riegel, Türgut Tukel, Malgorzata Krajewska-Walasek and Albert A. Schinzel

in Human Molecular Genetics

Volume 7, issue 5, pages 887-894
Published in print May 1998 | ISSN: 0964-6906
Published online May 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.5.887
High Level of Unequal Meiotic Crossovers at the Origin of the 22q11.2 and 7q11.23 Deletions

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Interstitial chromosomal deletions at 22q11.2 and 7q11.23 are detected in the vast majority of patients affected by CATCH 22 syndromes and the Williams-Beuren syndrome, respectively. In a group of 15 Williams-Beuren patients, we have shown previously that a large number of 7q11.23 deletions occur in association with an interchromosomal rearrangement, indicative of an unequal crossing-over event between the two homologous chromosomes 7. In this study, we show that a similar mechanism also underlies the formation of the 22q11.2 deletions associated with CATCH 22. In eight out of 10 families with a proband affected by CATCH 22, we were able to show that a meiotic recombination had occurred at the critical deleted region based on segregation analysis of grandparental haplotypes. The incidences of crossovers observed between the closest informative markers, proximal and distal to the deletion, were compared with the expected recombination frequencies between the markers. A significant number of recombination events occur at the breakpoint of deletions in CATCH 22 patients (P=2.99×10−7). The segregation analysis of haplotypes in three-generation families was also performed on an extended number of Williams-Beuren cases (22 cases in all). The statistically significant occurrence of meiotic crossovers (P=4.45×10−9) further supports the previous findings. Thus, unequal meiotic crossover events appear to play a relevant role in the formation of the two interstitial deletions. The recurrence risk for healthy parents in cases where such meiotic recombinations can be demonstrated is probably negligible. Such a finding is in agreement with the predominantly sporadic occurrence of the 22q11.2 and 7q11.23 deletions. No parent-of-origin bias was observed in the two groups of patients with regard to the origin of the deletion and to the occurrence of inter-versus intrachromosomal rearrangements.

Journal Article.  4375 words.  Illustrated.

Subjects: Genetics and Genomics

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