Allele-specific relative telomere lengths are inherited.

Previous studies have indicated that single relative telomere lengths are defined in the zygote. In order to explore the possibility that single telomere lengths segregate in families, we compared relative telomere lengths obtained from allelic chromosome extremities transmitted from parent to child, representing a total of 31 independent meiotic events. We find a significant positive correlation of 0.

The relative lengths of individual telomeres are defined in the zygote and strictly maintained during life.

Previous studies have indicated that average telomere length is partly inherited (Slagboom et al., 1994; Rufer et al., 1999) and that there is an inherited telomere pattern in each cell (Graakjaer et al.

Alternative lengthening of telomeres is characterized by high rates of telomeric exchange.

Telomere maintenance activity is a hallmark of cancer. In some telomerase-negative tumors, telomeres become lengthened by alternative lengthening of telomeres (ALT), a recombination-mediated DNA replication process in which telomeres use other telomeric DNA as a copy template. Using chromosome orientation fluorescence in situ hybridization, we found that postreplicative exchange events involving a telomere and another TTAGGG-repeat tract occur at remarkably high frequencies in ALT cells (range 28-280/100 metaphases) and rarely or never in non-ALT cells, including cell lines with very long telomeres.

The shortest telomeres drive karyotype evolution in transformed cells.

Maintenance of telomeres is essential for chromosome stability. In the absence of telomerase, telomeres shorten with cell division until they approach a stability threshold, at which point cells enter senescence. When senescence-signaling pathways are inactive, further telomere shortening leads to chromosome instability characterized by telomeric fusions and breakage-fusion-bridge (BFB) cycles.

Segmental polymorphisms in the proterminal regions of a subset of human chromosomes.

The subtelomeric domains of chromosomes are probably the most rapidly evolving structures of the human genome. The highly variable distribution of large duplicated subtelomeric segments has indicated that frequent exchanges between nonhomologous chromosomes may have been taking place during recent genome evolution. We have studied the extent and variability of such duplications using in situ hybridization techniques and a set of well-defined subtelomeric cosmid probes that identify discrete regions within the subtelomeric domain.