Haplotype diversity and sequence heterogeneity of human telomeres.
Haplotype diversity and sequence heterogeneity of human telomeres.
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DOI：
10.1101/gr.274639.120
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发表时间：
2021-07
期刊：
影响因子：
7
通讯作者：
Mason CE
中科院分区：
文献类型：
--
作者：
Grigorev K;Foox J;Bezdan D;Butler D;Luxton JJ;Reed J;McKenna MJ;Taylor L;George KA;Meydan C;Bailey SM;Mason CE
端粒是覆盖真核染色体末端的重复核苷酸序列区域，可防止染色体退化，其长度与年龄和不良健康风险因素相关。然而，鉴于其长度和重复性，端粒区域很难通过短读长测序进行重建，因此端粒测序、定位和变异解析成为具有挑战性的问题。最近，读长可达数百千碱基对的长读长测序技术使得常规读取端粒区域并检查其序列结构成为可能。在此，我们描述了一个从全基因组单分子测序实验中提取端粒读段的框架，包括端粒重复基序和重复类型的从头鉴定，还描述了它们的序列变异。我们发现长读长测序能够准确捕获长而复杂的端粒延伸和重复序列，观察到人类端粒广泛的序列异质性，发现并定位非规范的端粒序列基序（包括先前报道的以及新的基序），并在短读长序列数据中对其进行验证。这些数据揭示了端粒单倍型中重复序列在群体内和群体间的广泛多样性，显示端粒变异更多地来自父系遗传，并呈现了跨越三个不同祖先群体（阿什肯纳兹犹太人、中国人和犹他州人）的数千碱基对人类端粒单倍型的首个基序组成图谱，这有助于未来对遗传变异、衰老和基因组生物学的研究。
Telomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, and whose lengths can be correlated with age and adverse health risk factors. Yet, given their length and repetitive nature, telomeric regions are not easily reconstructed from short-read sequencing, thus making telomere sequencing, mapping, and variant resolution challenging problems. Recently, long-read sequencing, with read lengths measuring in hundreds of kilobase pairs, has made it possible to routinely read into telomeric regions and inspect their sequence structure. Here, we describe a framework for extracting telomeric reads from whole-genome single-molecule sequencing experiments, including de novo identification of telomere repeat motifs and repeat types, and also describe their sequence variation. We find that long, complex telomeric stretches and repeats can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize noncanonical telomere sequence motifs (both previously reported, as well as novel), and validate them in short-read sequence data. These data reveal extensive intra- and inter-population diversity of repeats in telomeric haplotypes, reveal higher paternal inheritance of telomeric variants, and represent the first motif composition maps of multi-kilobase-pair human telomeric haplotypes across three distinct ancestries (Ashkenazi, Chinese, and Utah), which can aid in future studies of genetic variation, aging, and genome biology.
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端粒：一种倍性 - 敏锐的方法，用于从整个基因组测序数据中估算端粒长度。
影响因子：
4.6
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
Butter, Falk
DOI：
10.1073/pnas.0501724102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Nordfjäll, K;Larefalk, Å;Roos, G
通讯作者：
Roos, G