High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: Implications for telomere biology and human evolution

The human Xp/Yp telomere-junction region exhibits high levels of sequence p olymorphism and linkage disequilibrium. To determine whether this is a gene ral feature of human telomeres, we have undertaken sequence analysis at the 12q telomere and have extended the analysis at Xp/Yp. A total of 22 single -nucleotide polymorphisms (SNPs) and one 30-bp duplication were detected in the 1,870 bp adjacent to the 12q telomere. Twenty polymorphic positions we re in almost complete linkage disequilibrium, creating three common diverge d haplotypes accounting for 80% of 12q telomeres in the white population. A further 6% of 12q telomeres contained a 1,439-bp deletion in the DNA flank ing the telomere. The remaining 13% of 12q telomeres did not amplify with t he primers used (nulls). The distribution of telomere (TTAGGG) and variant repeats within 12q telomeres was hypervariable, but alleles with similar di stribution patterns were associated with the same haplotype in the telomere -adjacent DNA. These data suggest that 12q telomeres, like Xp/Yp telomeres, exhibit low levels of homologous recombination and evolve along haploid li neages. In contrast, high levels of homologous recombination: occur in the adjacent proterminal regions of human chromosomes. This suggests that there is a localized telomere-mediated suppression of recombination. In addition , the genetic characteristics of these regions may provide a source of deep lineages for the study of early human evolution, unaffected by both natura l selection and recombination. To explain the presence of a few diverged ha plotypes adjacent to the Xp/Yp and 12q telomeres, we propose a model that i nvolves the hybridization of two archaic hominoid lineages ultimately givin g rise to modern Homo sapiens.