FISH Technology for Telomere Analysis

Analysis of the telomeric regions of human chromosomes is a significant challenge using conventional G-banding analysis. Patients reported to have normal karyotypes by conventional cytogenetics methods may actually have subtelomere rearrangements that have remained undetected as the cause of their abnormal phenotype. 

In order to improve the sensitivity in detecting subtelomere rearrangements, our laboratory was involved in an international collaboration to identify FISH probes for the unique subtelomeric regions of each human chromosome (National Institutes of Health et al., 1996; Knight and Lese et al., 2000).

The availability of unique subtelomere probes for all human chromosomes has allowed cytogenetic analysis to reach a new plateau. This technique has a higher resolution than G-banding analysis for identifying rearrangements and there is growing evidence that subtle deletions and duplications of human subtelomeric regions have failed to be ascertained by routine cytogenetic analysis.

In a study by Knight et al. (1999), 466 individuals with mild or moderate-severe mental retardation, who previously had a normal G-banding analysis, were examined for subtelomeric rearrangements. A subtelomeric rearrangement was identified in 7.4% of individuals with moderate-severe mental retardation and 0.5% of individuals with mild mental retardation.