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Title: Analysis of Crossover Breakpoints Yields New Insights into the Nature of the Gene Conversion Events Associated with Large NF1 Deletions Mediated by Nonallelic Homologous Recombination
Authors: Bengesser, Kathrin ×
Vogt, Julia
Mussotter, Tanja
Mautner, Victor-Felix
Messiaen, Ludwine
Cooper, David N
Kehrer-Sawatzki, Hildegard #
Issue Date: Feb-2014
Publisher: John Wiley & Sons, Inc.
Series Title: Human Mutation vol:35 issue:2 pages:215-26
Article number: 10.1002/humu.22473
Abstract: Large NF1 deletions are mediated by nonallelic homologous recombination (NAHR). An in-depth analysis of gene conversion operating in the breakpoint-flanking regions of large NF1 deletions was performed to investigate whether the rate of discontinuous gene conversion during NAHR with crossover is increased, as has been previously noted in NAHR-mediated rearrangements. All 20 germline type-1 NF1 deletions analysed were mediated by NAHR associated with continuous gene conversion within the breakpoint-flanking regions. Continuous gene conversion was also observed in 31/32 type-2 NF1 deletions investigated. In contrast to the meiotic type-1 NF1 deletions, type-2 NF1 deletions are predominantly of post-zygotic origin. Our findings therefore imply that the mitotic as well as the meiotic NAHR intermediates of large NF1 deletions are processed by long-patch mismatch repair (MMR), thereby ensuring gene conversion tract continuity instead of the discontinuous gene conversion that is characteristic of short-patch repair. However, the single type-2 NF1 deletion not exhibiting continuous gene conversion was processed without MMR, yielding two different deletion-bearing chromosomes which were distinguishable in terms of their breakpoint positions. Our findings indicate that MMR failure during NAHR, followed by post-meiotic/mitotic segregation, has the potential to give rise to somatic mosaicism in human genomic rearrangements by generating breakpoint heterogeneity. This article is protected by copyright. All rights reserved.
URI: 
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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