复旦大学徐书华等研究人员合作绘制出中国36个民族的泛基因组参考。2023年6月14日，《自然》杂志在线发表了这项成果。

研究人员展示了中国泛基因组联盟第一阶段的数据，包括基于代表36个中国少数民族的58个核心样本的116个高质量和单倍型从头组装。CPC核心组合的平均高保真长读序列覆盖率为30.65倍，平均毗连度N50超过35.63兆字节，平均总大小为3.01兆字节，为GRCh38增加了1.89亿个碱基对的常染色体多态性序列和1367个蛋白编码基因的复制。研究人员确定了1590万个小变体和78072个结构变体，其中590万个小变体和34223个结构变体没有在最近发布的泛基因组参考中报道。中国泛基因组联盟的数据表明，当来自代表性不足的少数民族群体个体被包括在内时，新的和缺失的序列发现率显著提高。缺失的参考序列富含古老的等位基因和赋予与角质化、对紫外线辐射的反应、DNA修复、免疫反应和寿命有关的基本功能基因，这意味着在揭示人类演化的新线索和恢复复杂疾病图谱中缺失的遗传性方面有很大的潜力。

据悉，人类基因组学正见证着从单一参考序列到泛基因组形式的持续范式转变，但亚洲血统的人群却没有得到充分的代表。

附：英文原文

Title: A pangenome reference of 36 Chinese populations

Author: Gao, Yang, Yang, Xiaofei, Chen, Hao, Tan, Xinjiang, Yang, Zhaoqing, Deng, Lian, Wang, Baonan, Kong, Shuang, Li, Songyang, Cui, Yuhang, Lei, Chang, Wang, Yimin, Pan, Yuwen, Ma, Sen, Sun, Hao, Zhao, Xiaohan, Shi, Yingbing, Yang, Ziyi, Wu, Dongdong, Wu, Shaoyuan, Zhao, Xingming, Shi, Binyin, Jin, Li, Hu, Zhibin, Lu, Yan, Chu, Jiayou, Ye, Kai, Xu, Shuhua

Issue&Volume: 2023-06-14

Abstract: Human genomics is witnessing an ongoing paradigm shift from a single reference sequence to a pangenome form, but populations of Asian ancestry are underrepresented. Here we present data from the first phase of the Chinese Pangenome Consortium, including a collection of 116 high-quality and haplotype-phased de novo assemblies based on 58 core samples representing 36 minority Chinese ethnic groups. With an average 30.65× high-fidelity long-read sequence coverage, an average contiguity N50 of more than 35.63megabases and an average total size of 3.01gigabases, the CPC core assemblies add 189million base pairs of euchromatic polymorphic sequences and 1,367 protein-coding gene duplications to GRCh38. We identified 15.9 million small variants and 78,072 structural variants, of which 5.9 million small variants and 34,223 structural variants were not reported in a recently released pangenome reference1. The Chinese Pangenome Consortium data demonstrate a remarkable increase in the discovery of novel and missing sequences when individuals are included from underrepresented minority ethnic groups. The missing reference sequences were enriched with archaic-derived alleles and genes that confer essential functions related to keratinization, response to ultraviolet radiation, DNA repair, immunological responses and lifespan, implying great potential for shedding new light on human evolution and recovering missing heritability in complex disease mapping.

DOI: 10.1038/s41586-023-06173-7

Source: https://www.nature.com/articles/s41586-023-06173-7