美国华盛顿大学医学院Evan E. Eichler团队近期取得重要工作进展。他们研究提出，人类基因组序列片段重复的结构多态性和多样性。相关研究成果2025年1月8日在线发表于《自然—遗传学》杂志上。

据介绍，片段重复（SD）对人类疾病、演化和多样性有着重大影响，但在序列层面一直难以解析清楚。

研究人员通过分析 170 个人类基因组组装数据（来自代表 38 名非洲人和 47 名非非洲人的 85 个样本），开展了一项针对SD的群体遗传学调查，在这些数据中，利用长读长序列组装技术，大多数常染色体上的SD已被完全解析。除去近端着丝粒染色体的短臂以及性染色体，研究人员鉴定出了1.732亿碱基对的重复序列（其中有4740万碱基对不存在于端粒到端粒的参考基因组中），从而区分出固定事件和结构多态性事件。

研究人员发现染色体内SD属于变异程度最高的那一类，罕见的重复事件定位在其原始序列附近。非洲人的基因组含有明显更多的染色体内SD，而且相较于非非洲人样本，其近期重复的基因家族更有可能具有更高的拷贝数。与一个包含 5.63 亿条全长转录本测序读长的资源进行对比后，研究人员确定了201个新的、可能具有编码蛋白质功能的基因，它们与这些拷贝数具有多态性的SD相对应。

附：英文原文

Title: Structural polymorphism and diversity of human segmental duplications

Author: Jeong, Hyeonsoo, Dishuck, Philip C., Yoo, DongAhn, Harvey, William T., Munson, Katherine M., Lewis, Alexandra P., Kordosky, Jennifer, Garcia, Gage H., Yilmaz, Feyza, Hallast, Pille, Lee, Charles, Pastinen, Tomi, Eichler, Evan E.

Issue&Volume: 2025-01-08

Abstract: Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.2Mb of duplicated sequence (47.4Mb not present in the telomere-to-telomere reference) distinguishing fixed from structurally polymorphic events. We find that intrachromosomal SDs are among the most variable, with rare events mapping near their progenitor sequences. African genomes harbor significantly more intrachromosomal SDs and are more likely to have recently duplicated gene families with higher copy numbers than non-African samples. Comparison to a resource of 563 million full-length isoform sequencing reads identifies 201 novel, potentially protein-coding genes corresponding to these copy number polymorphic SDs.

DOI: 10.1038/s41588-024-02051-8

Source: https://www.nature.com/articles/s41588-024-02051-8