Disclosing the mechanisms of origin of de novo short‐arm duplications of chromosome 9

Abstract

Three de novo short-arm duplications of chromosome 9 were investigated by fluorescence in situ hybridization (FISH) and genotyping of microsatellite loci with the aim of disclosing their mechanisms of origin. Two of these duplications were identified as direct and one as an inverted duplication, and they comprised nearly the entire 9p. In the two dirdup(9p), the distal breakpoints were mapped to subtelomeric sequences, whereas the proximal break boundaries were defined by pericentromeric sequences. The maternal origin of both duplications was demonstrated, and the presence of three different alleles in distal loci indicated that these rearrangements must have occurred prezygotically. In the invdup(9p), the proximal breakpoint was mapped at the alphoid sequences, which were partially duplicated on the tip of the rearranged 9p; subtelomeric and telomeric sequences were not detected, allowing the distal breakpoint to be mapped proximally to subtelomeric sequences. Genotyping of microsatellite loci allowed us to conclude that this invdup(9p) chromosome had a paternal origin. Homozygosity throughout the duplicated segment pointed to its probable postzygotic formation. Chromatid rearrangements appeared to have originated these 9p duplications, involving pericentromeric and subtelomeric sequences. These rearrangements might have been the result of recombination events between homologous repeats in these segments.