Title: Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions
Authors: Zickler, Antje M ×
Hampp, Stephanie
Messiaen, Ludwine
Bengesser, Kathrin
Mussotter, Tanja
Roehl, Angelika C
Wimmer, Katharina
Mautner, Victor-Felix
Kluwe, Lan
Upadhyaya, Meena
Pasmant, Eric
Chuzhanova, Nadia
Kestler, Hans A
Högel, Josef
Legius, Eric
Claes, Kathleen
Cooper, David N
Kehrer-Sawatzki, Hildegard #
Issue Date: 2012
Publisher: John Wiley & Sons, Inc.
Series Title: Human Mutation vol:33 issue:2 pages:372-383
Article number: 10.1002/humu.21644
Abstract: Nonallelic homologous recombination (NAHR) is the major mechanism underlying recurrent genomic rearrangements, including the large deletions at 17q11.2 that cause neurofibromatosis type 1 (NF1). Here we identify a novel NAHR hotspot, responsible for type-3 NF1 deletions which span 1.0-Mb. Breakpoint clustering within this 1-kb hotspot, termed PRS3, was noted in 10 of 11 known type-3 NF1 deletions. PRS3 is located within the LRRC37B pseudogene of the NF1-REPb and NF1-REPc low-copy repeats. In contrast to other previously characterized NAHR hotspots, PRS3 has not developed on a pre-existing allelic homologous recombination hotspot. Furthermore, the variation pattern of PRS3 and its flanking regions are unusual since only NF1-REPc (and not NF1-REPb) is characterized by a high SNP frequency, suggestive of uni-directional sequence transfer via nonallelic homologous gene conversion (NAHGC). By contrast, the previously described intense NAHR hotspots within the CMT1A-REPs, and the PRS1 and PRS2 hotspots underlying type-1 NF1 deletions, experience frequent bi-directional sequence transfer. PRS3 within NF1-REPc was also found to be involved in NAHGC with the LRRC37B gene, the progenitor locus of the LRRC37B-P duplicons, as indicated by the presence of shared SNPs between these loci. PRS3 therefore represents a weak (and probably evolutionarily rather young) NAHR hotspot with unique properties. ©2011 Wiley Periodicals, Inc.
ISSN: 1059-7794
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Neurofibromatosis Research
× corresponding author
# (joint) last author

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