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Nature:发布人类X染色体完成图,开启基因组学研究新纪元

2020-07-17 生物探索 生物探索

美国国立卫生研究院(NIH)的下属国家人类基因组研究所(NHGRI)的研究人员已经生产出人类染色体的第一个端对端DNA序列。近日发表在《Nature》杂志上的相关研究报告表明,研究人员有可能生成一个精

美国国立卫生研究院(NIH)的下属国家人类基因组研究所(NHGRI)的研究人员已经生产出人类染色体的第一个端对端DNA序列。近日发表在《Nature》杂志上的相关研究报告表明,研究人员有可能生成一个精确的人染色体逐个碱基序列,这将加速人基因组完整序列的问世。

https://doi.org/10.1038/s41586-020-2547-7

NHGRI主任、医学博士Eric Green说:“这项研究开启了基因组学研究的新纪元。能够生成真正完整的染色体和基因组序列的能力是一项技术专长,将有助于我们全面了解基因组功能,并为医学护理中基因组信息的使用提供信息。”

2003年,研究人员首次完成了人类基因组的测序工作。随着研究的不断深入和技术的不断进步,人类基因组成为有史以来最精确和最完整的脊椎动物基因组序列。然而,目前仍然存在数百个未知的缺口或缺失的DNA序列,其中包含着难以识别的重复DNA片段,可能覆盖了与人类健康和疾病有关的基因和其他功能元件。

人类基因组中大约有60亿个碱基,而DNA测序仪无法一次全部读取。因此,研究人员将基因组切成较小的片段,然后分析每个片段,一次产生数百个碱基的序列,并将这些较短的DNA序列重新组合。

在这项研究中,研究人员首先选取了X染色体序列进行测序,因为它与无数的X染色体疾病相关,包括血友病,慢性肉芽肿病和杜氏肌营养不良症等。

不过,研究人员没有对正常人类细胞的X染色体进行测序,而是使用了一种有两个相同的X染色体的特殊细胞类型。与仅具有X染色体单拷贝的男性细胞相比,这种细胞可提供更多的DNA进行测序。它还可以避免分析典型女性细胞的两个X染色体时遇到的序列差异问题。

图像描绘了DNA序列的拼图碎片。图片来源:Ernesto del Aguila III(NHGRI)

借助新的测序技术和分析方法,研究人员对人类X染色体进行了分析,随后用新开发的计算机程序组装生成了序列的许多片段,并尽力缩小X染色体上最大的剩余序列缺口,这是在染色体中间部分(着丝粒)发现的大约300万个重复DNA碱基。

由于没有可供评估组装这种高度重复的DNA序列准确性的方法,研究人员执行了几个验证步骤以帮助确认所生成序列的有效性。

该报告的作者Karen Miga博士说:“我们知道基因组中这些以前未知的位点在个体之间是非常不同的,但是重要的是开始弄清楚这些差异如何导致人类生物学和疾病。”

据悉,这项研究是Telomere-to-Telomere (T2T) consortium计划的一部分,该计划由NHGRI部分资助,旨在产生人类基因组的完整参考序列。目前,T2T正在继续努力处理剩余的人类染色体,以期在2020年产生完整的人类基因组序列。

原始出处:

Karen H. Miga, Sergey Koren, Adam M. Phillippy, et.al. Telomere-to-telomere assembly of a complete human X chromosome. Nature 14 July 2020

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    2021-04-03 liye789132251
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    2020-09-16 xuyu
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    2021-03-28 zutt
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