The study of de novo balanced chromosome rearrangements associated with phenotypic alterations is a valuable tool for understanding pathogenic mechanisms, as such rearrangements can reveal gene disruptions and their functional consequences in patients. Since balanced rearrangements do not involve copy number changes, standard chromosome microarray analysis is ineffective for investigating these cases. Therefore, a modified approach known as array painting may be applied to identify the chromosomal breakpoints. In this method, only the rearranged chromosomes—or specific segments containing the rearrangement—are isolated by microdissection, differentially labeled with distinct fluorochromes, and hybridized onto a CGH array. The breakpoint is identified by the transition point between the two fluorochrome signals on the array. The resolution of array painting depends primarily on the type of array, the density of its probes, and the repetitive nature of the DNA sequence at the breakpoint site.

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Breakpoint Mapping of Balanced Chromosomal Rearrangements Using Array-CGH with Microdissection-Derived FISH Probes

  • Maria Isabel Melaragno,
  • Mariana Moysés-Oliveira

摘要

The study of de novo balanced chromosome rearrangements associated with phenotypic alterations is a valuable tool for understanding pathogenic mechanisms, as such rearrangements can reveal gene disruptions and their functional consequences in patients. Since balanced rearrangements do not involve copy number changes, standard chromosome microarray analysis is ineffective for investigating these cases. Therefore, a modified approach known as array painting may be applied to identify the chromosomal breakpoints. In this method, only the rearranged chromosomes—or specific segments containing the rearrangement—are isolated by microdissection, differentially labeled with distinct fluorochromes, and hybridized onto a CGH array. The breakpoint is identified by the transition point between the two fluorochrome signals on the array. The resolution of array painting depends primarily on the type of array, the density of its probes, and the repetitive nature of the DNA sequence at the breakpoint site.