De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation.
De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation.
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西藏基因组的从头组装以及与高海拔适应相关的新型结构变异的鉴定
DOI：
10.1093/nsr/nwz160
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发表时间：
2020-02
影响因子：
20.6
通讯作者：
Su B
中科院分区：
文献类型：
--
作者：
Ouzhuluobu;He Y;Lou H;Cui C;Deng L;Gao Y;Zheng W;Guo Y;Wang X;Ning Z;Li J;Li B;Bai C;Baimakangzhuo;Gonggalanzi;Dejiquzong;Bianba;Duojizhuoma;Liu S;Wu T;Xu S;Qi X;Su B
结构变异（SV）可能在人类适应高海拔等极端环境方面发挥重要作用，但尚未得到充分研究。在这里，结合长读段测序和多支架技术，我们组装了一个高质量的西藏基因组（ZF 1），重叠群N50长度为24.57兆碱基对（Mb），支架N50长度为58.80 Mb。ZF 1组装体填补了参考人类基因组（GRCh 38）中剩余的80个N-空位（总长度为0.25 Mb）。明显地，我们检测到17 900个SV，其中ZF 1特异性SV富含GT3活性，这是激活缺氧通路所需的。进一步的人群分析发现MKL 1基因中存在163个碱基的内含子缺失，表明高原藏族和低地汉族之间存在很大差异。这种缺失与藏族人的关键适应性生理特征之一--较低的肺动脉收缩压显著相关。此外，通过使用高质量的从头组装，我们观察到全基因组古代人科动物（阿尔泰尼安德特人和丹尼索瓦人）在ZF 1中共享非参考序列的比率（1.32%-1.53%）比其他东亚基因组（0.70%-0.98%）高得多，反映了西藏人独特的基因组组成。一个这样的古人类共享序列-SCUBE 2基因中的662 bp内含子插入-在西藏人中富集并与更好的肺功能（FEV 1/FVC比值）相关。总的来说，我们产生了第一个高分辨率的西藏参考基因组，鉴定的SV可能是未来进化和医学研究的宝贵资源。
Structural variants (SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome (ZF1), with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38). Markedly, we detected 17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (1.32%–1.53%) compared to other East Asian genomes (0.70%–0.98%), reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a 662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.
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巨核细胞白血病 1 指导组蛋白 H3 赖氨酸 4 甲基转移酶复合物调节缺氧性肺动脉高压
影响因子：
8.3
作者：
Chen, Dewei;Yang, Yuyu;Xu, Yong
通讯作者：
Xu, Yong
影响因子：
10.7
作者：
Arciero E;Kraaijenbrink T;Asan;Haber M;Mezzavilla M;Ayub Q;Wang W;Pingcuo Z;Yang H;Wang J;Jobling MA;van Driem G;Xue Y;de Knijff P;Tyler-Smith C
通讯作者：
Tyler-Smith C
影响因子：
48
作者：
Sedlazeck FJ;Rescheneder P;Smolka M;Fang H;Nattestad M;von Haeseler A;Schatz MC
通讯作者：
Schatz MC
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang
影响因子：
4.5
作者：
Bigham A;Bauchet M;Pinto D;Mao X;Akey JM;Mei R;Scherer SW;Julian CG;Wilson MJ;López Herráez D;Brutsaert T;Parra EJ;Moore LG;Shriver MD
通讯作者：
Shriver MD