Closing in on Telomeric Closure

The mapping of STS markers to subtelomeric chromosome regions is complicated by unique features of subtelomeric DNA. Low-copy repeat elements are very abundant in subtelomeric regions and thus cause problems in generating robust, locus-specific STSs. An STS priming site in a repeat sequence alters the effective ratios of primers in the PCR reaction (making the assay less reliable), and the two STS priming sites in a low-copy repeat result in the generation of an STS that maps to multiple genomic sites (sometimes on the same chromosome). YAC-based STS content map information is extremely limited in subtelomeric chromosome regions because YAC clones carrying this DNA are under-represented in most YAC libraries. Conventional YACs derived from subtelomeric regions are often prone to rearrangement. Finally, because the positioning of STS markers at the ends of maps is constrained only by mapping data from one side of the marker, there is a tendency for “problem” markers with genotyping ambiguity or error to be positioned at the ends of maps rather than within maps (where their position is more rigorously constrained by mapping data from flanking markers on both sides).

In sum, robust, single-copy STS-based markers for distal subtelomeric regions are difficult to find; subtelomeric marker orders based on genetic linkage, radiation hybrid (RH), and STS content mapping methods are more error-prone than normal, and clone coverage of most subtelomeric regions in YAC libraries is sparse. If subtelomeric regions were not so interesting, it might be wise to avoid them entirely. However, subtelomeric regions are interesting. They have enhanced levels of recombination, very high gene densities, …