Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions.
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Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions. / Zickler, Antje M; Hampp, Stephanie; Messiaen, Ludwine; Bengesser, Kathrin; Mussotter, Tanja; Roehl, Angelika C; Wimmer, Katharina; Mautner, Viktor Felix; Kluwe, Lan; Upadhyaya, Meena; Pasmant, Eric; Chuzhanova, Nadia; Kestler, Hans A; Högel, Josef; Legius, Eric; Claes, Kathleen; Cooper, David N; Kehrer-Sawatzki, Hildegard.
In: HUM MUTAT, Vol. 33, No. 2, 2, 2012, p. 372-383.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions.
AU - Zickler, Antje M
AU - Hampp, Stephanie
AU - Messiaen, Ludwine
AU - Bengesser, Kathrin
AU - Mussotter, Tanja
AU - Roehl, Angelika C
AU - Wimmer, Katharina
AU - Mautner, Viktor Felix
AU - Kluwe, Lan
AU - Upadhyaya, Meena
AU - Pasmant, Eric
AU - Chuzhanova, Nadia
AU - Kestler, Hans A
AU - Högel, Josef
AU - Legius, Eric
AU - Claes, Kathleen
AU - Cooper, David N
AU - Kehrer-Sawatzki, Hildegard
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Humans
KW - Base Sequence
KW - Polymorphism, Single Nucleotide
KW - Gene Deletion
KW - Gene Order
KW - Carrier Proteins/genetics
KW - Chromosome Breakpoints
KW - Gene Conversion
KW - Genes, Neurofibromatosis 1
KW - Homologous Recombination
KW - Mosaicism
KW - Neurofibromatosis 1/genetics
KW - Nucleotide Motifs
KW - Humans
KW - Base Sequence
KW - Polymorphism, Single Nucleotide
KW - Gene Deletion
KW - Gene Order
KW - Carrier Proteins/genetics
KW - Chromosome Breakpoints
KW - Gene Conversion
KW - Genes, Neurofibromatosis 1
KW - Homologous Recombination
KW - Mosaicism
KW - Neurofibromatosis 1/genetics
KW - Nucleotide Motifs
M3 - SCORING: Journal article
VL - 33
SP - 372
EP - 383
JO - HUM MUTAT
JF - HUM MUTAT
SN - 1059-7794
IS - 2
M1 - 2
ER -