Both authors contributed equally to this work.
Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions†
Article first published online: 9 DEC 2011
© 2011 Wiley Periodicals, Inc.
Volume 33, Issue 2, pages 372–383, February 2012
How to Cite
Zickler, A. M., Hampp, S., Messiaen, L., Bengesser, K., Mussotter, T., Roehl, A. C., Wimmer, K., Mautner, V.-F., Kluwe, L., Upadhyaya, M., Pasmant, E., Chuzhanova, N., Kestler, H. A., Högel, J., Legius, E., Claes, K., Cooper, D. N. and Kehrer-Sawatzki, H. (2012), Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions. Hum. Mutat., 33: 372–383. doi: 10.1002/humu.21644
Communicated by Claude Ferec
- Issue published online: 12 JAN 2012
- Article first published online: 9 DEC 2011
- Accepted manuscript online: 1 NOV 2011 03:39PM EST
- Manuscript Accepted: 6 OCT 2011
- Manuscript Received: 14 JUL 2011
- DFG-grant (KE 724/11-1)
- nonallelic homologous recombination hotspot;
- neurofibromatosis type 1;
- gene conversion
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 that 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 preexisting allelic homologous recombination hotspot. Furthermore, the variation pattern of PRS3 and its flanking regions is unusual since only NF1-REPc (and not NF1-REPb) is characterized by a high single nucleotide polymorphism (SNP) frequency, suggestive of unidirectional 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 bidirectional 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. Hum Mutat 33:372–383, 2012. © 2011 Wiley Periodicals, Inc.