The analysis of variation at human autosomal telomeres

The terminal regions of 7q and 12q show a high level of similarity (96 %) for at least 2 kb of DNA adjacent to the telomere. In addition, the start of the telomere repeat arrays coincide with respect to the flanking DNA at these two chromosome ends. This suggests that a duplication has occurred and that the proximal region of the telomere was involved. The 7q and 12q telomere-adjacent regions contain a diverged subterminal repeat that suggests multiple rearrangements have been involved in the formation of the modern 7q and 12q telomeres. A polymorphic telomere (the 'Nitru' telomere) has been isolated, and is located at 16p and 16q. The telomere-adjacent sequence from the Nitu telomere is present on 18 autosomes, but it is only adjacent to a telomere repeat array at these two chromosome ends. The Nitu telomere is present in approximately 8 % of individuals from various populations.;Analysis of the interspersion patterns of TTAGGG and variant repeats, at the proximal end of these three autosomal telomeres, indicates that there is no similarity between them. The 7q and 12q telomeres can be distinguished easily despite the similarity in the flanking DNA. The Nitu telomere repeat arrays are different again, although it is not possible to determine the location (16p or 16q) by the telomere interspersion pattern or the 200 bp of DNA immediately adjacent. This may suggest that the Nitu telomere duplication is relatively recent. Analysis of single alleles at the 12q and Nitu telomeres demonstrates a high level of variation, suggesting a high level of turnover. The allelic variation within these autosomal telomeres indicates that the major mechanism involved in the turnover of repeats is intra-allelic.