FISHing for mechanisms of cytogenetically defined terminal deletions usingchromosome-specific subtelomeric probes

Cytogenetically defined terminal deletions are thought to be a major, yet u nderappreciated, cause of mental retardation and multiple congenital anomal ies. The mechanisms by which terminal deletions arise and are stabilized ar e not completely understood; although all ends of human chromosomes must ha ve a telomeric cap to be stable. At least three mechanisms exist to maintai n chromosome ends with cytogenetically defined terminal deletions: stabiliz ation of terminal deletions through a process of telomere regeneration (ter med 'telomere healing'), retention of the original telomere producing inter stitial deletions, and formation of derivative chromosomes by obtaining a d ifferent telomeric sequence through cytogenetic rearrangement (termed 'telo mere capture'). We used chromosome-specific subtelomeric probes and FISH to characterize cytogenetically defined terminal deletions in patients with 1 p36 monosomy. Based on the current resolution of these subtelomeric probes, our results indicate that cytogenetically defined terminal deletions of 1p 36 are likely to occur through all three mechanisms, although we speculate that the majority of cases were stabilized through telomere regeneration. T hese results demonstrate the use of chromosome-specific subtelomeric probes as an efficient first step toward uncovering the mechanisms that result in the stabilization of cytogenetically defined terminal deletions.