自然杂志 >

2024 , Vol. 46 >Issue 2: 88 - 94

DOI: https://doi.org/10.3969/j.issn.0253-9608.2024.02.002

特约专稿

“端粒到端粒”人类参考基因组：精准医学时代的新起点

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  • 中国科学院北京基因组研究所(国家生物信息中心)，北京 100101
康禹，研究方向：医学基因组学、基因检测和分析新技术。

收稿日期: 2024-02-19

  网络出版日期: 2024-04-19

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T2T human reference genomes mark the new starting point of the precision medicine era

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  • Beijing Institute of Genomics, Chinese Academy of Sciences/China National Center for Bioinformation, Beijing 100101, China

Received date: 2024-02-19

  Online published: 2024-04-19

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摘要

DNA测序技术的飞速发展使人类基因组学研究迈进“端粒到端粒(T2T)时代”。这个时代的核心标志是实现每一个人类染色体分子——从端粒到端粒——高质量、高完整度的连续线性组装，成为精准医学质量控制的金标准，从而准确和稳定地识别个体变异信息。越来越多个体基因组的完整组装为我们揭示远高于预期的人类基因组差异，也为各人群采用自己的近缘参考基因组进行变异分析提供了关键的理论依据。近缘参考基因组可以更准确地识别和定位个体的基因变异，而准确的变异数据是精准医学中变异与表型关联研究的关键数据基础。这种以人群为单位的基因组分析和研究新范式，必将显著影响国际和国内未来精准医学发展的格局。

关键词： 人类基因组计划; 测序技术; 端粒到端粒(T2T)基因组拼接; 参考基因组; 精准医学; 医学基因组大数据; 基因组诊断和治疗

本文引用格式

康禹 . “端粒到端粒”人类参考基因组：精准医学时代的新起点[J]. 自然杂志, 2024 , 46(2) : 88 -94 . DOI: 10.3969/j.issn.0253-9608.2024.02.002

Abstract

Driven by the rapid advancement of DNA sequencing technology, human genome research entered the era of “telomere to telomere (T2T)”. The central hallmark of this era is achieving high-quality and high-continuity linear assembly of every human chromosome molecule, from telomere to telomere, which could be served as the gold standard for quality control in precision medicine. This enables accurate and stable identification of individual variation information. The complete assembly of an increasing number of individual genomes has revealed significantly higher levels of human genome variations than initially anticipated. It has also provided a crucial theoretical foundation for each population to utilize its own reference genome for variation analysis. By employing a closely matched reference genome, it would be more precise in identification and locating individual variations. Dataset of accurate variation information forms the fundamental basis for studying the association between variations and phenotypes in precision medicine. This novel paradigm based on population-based genome analysis and research will undoubtedly have a significant impact on the future development of precision medicine.

Key words： Human Genome Project, sequencing technology, telomere to telomere (T2T) genome assembly, reference genome, ; precision medicine, big data of medical genomics, genomic diagnosis and therapy

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