title: Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions.
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 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.
authors: Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany.
authors: Antje M
authors: AM
authors: Zickler
authors: Stephanie
authors: S
authors: Hampp
authors: Ludwine
authors: L
authors: Messiaen
authors: Kathrin
authors: K
authors: Bengesser
authors: Tanja
authors: T
authors: Mussotter
authors: Angelika C
authors: AC
authors: Roehl
authors: Katharina
authors: K
authors: Wimmer
authors: Victor-Felix
authors: VF
authors: Mautner
authors: Lan
authors: L
authors: Kluwe
authors: Meena
authors: M
authors: Upadhyaya
authors: Eric
authors: E
authors: Pasmant
authors: Nadia
authors: N
authors: Chuzhanova
authors: Hans A
authors: HA
authors: Kestler
authors: Josef
authors: J
authors: Högel
authors: Eric
authors: E
authors: Legius
authors: Kathleen
authors: K
authors: Claes
authors: David N
authors: DN
authors: Cooper
authors: Hildegard
authors: H
authors: Kehrer-Sawatzki
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D056905:Chromosome Breakpoints; D005785:Gene Conversion; D017353:Gene Deletion; D023061:Gene Order; D016514:Genes, Neurofibromatosis 1; D059765:Homologous Recombination; D006801:Humans; D009030:Mosaicism; D009456:Neurofibromatosis 1 / Q000235:genetics*; D059372:Nucleotide Motifs; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins