De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation

KIZ OpenIR > 科研部门 > 比较基因组学（宿兵）

	De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation
	Ouzhuluobu; He, Yaoxi; Lou, Haiyi; Cui, Chaoying; Deng, Lian; Gao, Yang; Zheng, Wangshan; Guo, Yongbo; Wang, Xiaoji; Ning, Zhilin; Li, Jun; Li, Bin; Bai, Caijuan; Baimakangzhuo; Gonggalanzi; Dejiquzong; Bianba; Duojizhuoma; Liu, Shiming; Wu, Tianyi; Xu, Shuhua; Qi, Xuebin; Su, Bing
	2020
发表期刊	NATIONAL SCIENCE REVIEW
ISSN	2095-5138
卷号	7 期号:2 页码:391-402
摘要	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.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12792
专题	科研部门_比较基因组学（宿兵）
推荐引用方式 GB/T 7714	Ouzhuluobu,He, Yaoxi,Lou, Haiyi,et al. De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation[J]. NATIONAL SCIENCE REVIEW,2020,7(2):391-402.
APA	Ouzhuluobu.,He, Yaoxi.,Lou, Haiyi.,Cui, Chaoying.,Deng, Lian.,...&Su, Bing.(2020).De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation.NATIONAL SCIENCE REVIEW,7(2),391-402.
MLA	Ouzhuluobu,et al."De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation".NATIONAL SCIENCE REVIEW 7.2(2020):391-402.

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