Intrachromosomal mitotic nonallelic homologous recombination is the major molecular mechanism underlying type‐2 NF1 deletions

摘要: Nonallelic homologous recombination (NAHR) is responsible for the recurrent rearrangements that give rise to genomic disorders. Although meiotic NAHR has been investigated in multiple contexts, much less known about mitotic despite its importance tumorigenesis. Because type-2 NF1 microdeletions frequently result from NAHR, they represent a good model which investigate features of NAHR. We have used microsatellite analysis and SNP arrays distinguish between various alternative recombinational possibilities, thereby ascertaining 17 18 deletions, with breakpoints SUZ12 gene highly pseudogene, originated via intrachromosomal recombination. This high proportion causing somatic deletions contrasts interchromosomal origin germline type-1 microdeletions, whose are located within NF1-REPs (low-copy repeats adjacent sequences). Further, occurs hotspots characterized by GC-content DNA duplex stability, whereas associated events here do not cluster regions significantly lower stability. Our findings therefore point fundamental mechanistic differences determinants