High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: Implications for telomere biology and human evolution
High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: Implications for telomere biology and human evolution
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DOI：
10.1086/302721
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发表时间：
2000-01-01
影响因子：
9.8
通讯作者：
Royle, NJ
中科院分区：
文献类型：
--
作者：
Baird, DM;Coleman, J;Royle, NJ
人类 Xp/Yp 端粒连接区表现出高水平的序列多态性和连锁不平衡。为了确定这是否是人类端粒的普遍特征，我们对 12q 端粒进行了序列分析，并在 Xp/Yp 处扩展了分析。在 12q 端粒附近的 1,870 bp 中总共检测到 22 个单核苷酸多态性 (SNP) 和 1 个 30 bp 重复。 20个多态性位置几乎完全连锁不平衡，产生三种常见的分歧单倍型，占白人12q端粒的80%。另外 6% 的 12q 端粒在端粒两侧的 DNA 中包含 1,439 bp 的缺失。剩余 13% 的 12q 端粒未使用所使用的引物进行扩增（无效）。端粒 (TTAGGG) 和 12q 端粒内变异重复的分布高度可变，但具有相似分布模式的等位基因与端粒相邻 DNA 中的相同单倍型相关。这些数据表明，12q 端粒，如 Xp/Yp 端粒，表现出低水平的同源重组，并沿着单倍体谱系进化。相反，高水平的同源重组：发生在人类染色体的邻近末端区域。这表明存在局部端粒介导的重组抑制。此外，这些区域的遗传特征可能为研究早期人类进化提供深层谱系的来源，而不受自然选择和重组的影响。为了解释 Xp/Yp 和 12q 端粒附近存在一些不同的单倍型，我们提出了一个模型，该模型涉及两个古老的类人猿谱系的杂交，最终产生了现代智人。
The human Xp/Yp telomere-junction region exhibits high levels of sequence polymorphism and linkage disequilibrium. To determine whether this is a general 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 were in almost complete linkage disequilibrium, creating three common diverged 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 flanking the telomere. The remaining 13% of 12q telomeres did not amplify with the primers used (nulls). The distribution of telomere (TTAGGG) and variant repeats within 12q telomeres was hypervariable, but alleles with similar distribution 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 lineages. 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 natural selection and recombination. To explain the presence of a few diverged haplotypes adjacent to the Xp/Yp and 12q telomeres, we propose a model that involves the hybridization of two archaic hominoid lineages ultimately giving rise to modern Homo sapiens.