MECHANISMS UNDERLYING TELOMERE REPEAT TURNOVER, REVEALED BY HYPERVARIABLE VARIANT REPEAT DISTRIBUTION PATTERNS IN THE HUMAN XP YP TELOMERE/

Sequences immediately adjacent to the human Xp/Yp telomere exhibit a h igh frequency of base substitutional polymorphisms, together with almo st complete linkage disequilibrium, to create only a few diverged hapl otypes, This sequence divergence has been used to develop a PCR-based system for mapping the distribution of the telomere (TTAGGG) and varia nt repeats (TGAGGG and TCAGGG) at the proximal end of the telomere rep eat array, The distribution of these repeats is extremely variable, Al most all Xp/Yp telomeres are different, indicating a high mutation rat e. Some telomere maps associated with the same flanking haplotype show similarities, identifying subsets of telomeres that share a recent co mmon ancestry, Mechanisms underlying the rapid turnover of repeats at the proximal end of the Xp/Yp telomere include intraallelic processes, such as slippage during replication, Inter-allelic exchanges may occu r occasionally, but telomerase activity probably plays only a minor ro le in the germline turnover of proximally located telomere and variant repeats.