检索结果-南通市图书馆

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

引用

National Science Review 2020年第2期7卷 391-402页

作者： Ouzhuluobu Yaoxi He Haiyi Lou Chaoying Cui Lian Deng Yang Gao Wangshan Zheng Yongbo Guo Xiaoji Wang Zhilin Ning Jun Li Bin Li Caijuan Bai baimakangzhuo Gonggalanzi Dejiquzong Bianba Duojizhuoma Shiming Liu Tianyi Wu Shuhua Xu Xuebin Qi Bing Su Collaborative Innovation Center of Genetics and Development High Altitude Medical Research Center School of Medicine Tibetan University Fukang Obstetrics Gynecology and Children Branch Hospital Tibetan Fukang Hospital State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Chinese Academy of Sciences Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational Biology Shanghai Institute of Nutrition and Health Shanghai Institutes for Biological SciencesUniversity of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Center for Disease Control Tibet Autonomous Region National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

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 detected17 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—a662-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.

关键词： long-read sequencing Tibetan structural variants genetic adaptation reference genome

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia

引用

National Science Review 2018年第4期5卷 516-529页

作者： Yaoxi He Xuebin Qi Ouzhuluobu Shiming Liu Jun Li Hui Zhang baimakangzhuo Caijuan Bai Wangshan Zheng Yongbo Guo Duojizhuoma Baimayangji Dejiquzong Bianba Gonggalanzi Yongyue Pan Qula Cirenyangji Wei Guo Yangla Yi Peng Xiaoming Zhang Kun Xiang Zhaohui Yang Liangbang Wang Gengdeng Yanfeng Zhang Tianyi Wu Bing Su Chaoying Cui State Key Laboratoryof Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences High Altitude Medical Research Center School of Medicine Tibetan University National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Fukang International Medical Examination Center Fukang Obstetrics Gynecologyand Children Branch Hospital Tibetan Fukang Hospital 7. Yunnan Key Laboratory of Primate Biomedicine ResearchInstitute of PrimateTranslational MedicineKunming University of Science andTechnology

Nitric oxide(NO) is an important molecule for vasomotor tone, and elevated NO signaling was previously hypothesized as a unique and adaptive physiological change in highland Tibetans. However, there has been lack of NO data from Tibetans living at low altitude and lowlander immigrants living at high altitude, which is crucial to test this hypothesis. Here, through cross-altitude(1990–5018 m) and cross-population(Tibetans and Han Chinese) analyses of serum NO metabolites(NOx) of 2086 individuals, we demonstrate that although Tibetans have a higher serum NOx level compared to lowlanders, Han Chinese immigrants living at high altitude show an even higher level than Tibetans. Consequently, our data contradict the previous proposal of increased NO signaling as the unique adaptive strategy in Tibetans.Instead, Tibetans have a relatively lower circulating NOx level at high altitude. This observation is further supported by data from the hypoxic experiments using human umbilical vein endothelial cells and gene knockout mice. No difference is detected between Tibetans and Han Chinese for endothelial nitric oxide synthase(e NOS), the key enzyme for circulating NO synthesis, suggesting that e NOS itself is unlikely to be the cause. We show that other NO synthesis-related genes(e.g. GCH1) carry Tibetan-enriched mutations significantly associated with the level of circulating NOx in Tibetans. Furthermore, gene network analysis revealed that the downregulation and upregulation of NOx is possibly achieved through distinct pathways.Collectively, our findings provide novel insights into the physiological and genetic mechanisms of the evolutionary adaptation of Tibetans to high-altitude hypoxia.

关键词： adaptation high altitude Tibetan nitric oxide GCH1

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

GCH1 plays a role in the high-altitude adaptation of Tibetans

引用

Zoological Research 2017年第3期38卷 155-162页

作者： Yong-Bo Guo Yao-Xi He Chao-Ying Cui Ouzhuluobu baimakangzhuo Duojizhuoma Dejiquzong Bianba Yi Peng Cai-juan Bai Gonggalanzi Yong-Yue Pan Qula Kangmin Cirenyangji Baimayangji Wei Guo Yangla Hui Zhang Xiao-Ming Zhang Wang-Shan Zheng Shu-Hua Xu Hua Chen Sheng-Guo Zhao Yuan Cai Shi-Ming Liu Tian-Yi Wu Xue-Bin Qi Bing Su College of Animal Science and Technology Gansu Agricultural University Lanzhou Gansu 730070 China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China High Altitude Medical Research Center School of Medicine Tibetan University Lhasa Tibet 850000 China Kunming College of Life Science University of Chinese Academy of Sciences Kunming Yunnan 650204 China Chinese Academy of Sciences Key Laboratory of Computational Biology Max Planck Independent Research Group on Population Genomics CAS-MPG Partner Institute for Computational Biology (PICB) Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China Center for Computational Genomics Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Xining Qinghai 810012 China School of Life Science and Technology Shanghai Tech University Shanghai 200031 China Collaborative Innovation Center of Genetics and Development Shanghai 200438 China

Tibetans are welt adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene （GCH1, GTP-cyclohydrolase I）, involved in maintaining nitric oxide synthetase （NOS） function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans Combined with previously published data, we demonstrated many GCHI variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.

关键词： GCH1 Positive selection TibetanHypoxia adaptation Nitric oxide HemoglobinOxygen saturation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production

引用

Zoological Research 2017年第3期38卷 163-170页

作者： Wang-Shan Zheng Yao-Xi He Chao-Ying Cui Ouzhuluobu Dejiquzong Yi Peng Cai-Juan Bai Duojizhuoma Gonggalanzi Bianba baimakangzhuo Yong-Yue Pan Qula Kangmin Cirenyangji Baimayangji Wei GUO Yangla Hui Zhang Xiao-Ming Zhang Yong-Bo Guo Shu-Hua Xu Hua Chen Sheng-Guo Zhao Yuan Cai Shi-Ming Liu Tian-Yi Wu Xue-Bin Qi Bing Su College of Animal Science and Technology Gansu Agricultural University Lanzhou Gansu 730070 China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China High Altitude Medical Research Center School of Medicine Tibetan University Lhasa Tibet 850000 China Kunming College of Life Science University of Chinese Academy of Sciences Kunming Yunnan 650204 China Chinese Academy of Sciences Key Laboratory of Computational Biology Max Planck Independent Research Group on Population Genomics CAS-MPG Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy ofSciences Shanghai 200031 China Center for Computational Genomics Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China National Key Laboratory of High Altitude Medicine High Altitude Medical Research Institute Xining Qinghai 810012 China School of Life Science and Technology Shanghai Tech University Shanghai 200031 China Collaborative Innovation Center of Genetics and Development Shanghai 200438 China

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.

关键词： Tibetans High altitude Hypoxia EP300 Genetic adaptation Nitric oxide

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

高原脑水肿小鼠模型的建立与鉴定

引用

四川大学学报（医学版） 2023年第6期54卷 1269-1275页

作者：春花白玛康卓西藏大学医学院拉萨850000

目的建立高原脑水肿(high altitude cerebral edema, HACE)动物模型,探寻能导致明显HACE临床表征的海拔条件,为进一步研究HACE的发病机制和干预策略奠定基础。方法选取8周龄雄性BALB/c小鼠,分为对照组(Control)和HACE组。Control组常... 详细信息

目的建立高原脑水肿(high altitude cerebral edema, HACE)动物模型,探寻能导致明显HACE临床表征的海拔条件,为进一步研究HACE的发病机制和干预策略奠定基础。方法选取8周龄雄性BALB/c小鼠,分为对照组(Control)和HACE组。Control组常压常氧处理(10只);HACE组置于低压低氧舱内,模拟4 000 m、5 000 m、6 000 m海拔高度,分别处理6 h、12 h、24 h、48 h、72 h,每个海拔高度每时点处死10只。HE染色观察脑组织形态学改变,以选择合适的模拟海拔建立显著的HACE模型并鉴定造模结果。HACE模型鉴定方法:称重检测脑水肿,Evans blue(EB)检测血脑屏障(brain-blood barrier, BBB)通透性、免疫荧光染色检测细胞凋亡情况。结果海拔4 000 m和5 000 m时无小鼠死亡,海拔6 000 m时小鼠死亡率为12.2%。HE染色显示脑组织形态和结构在海拔4 000 m无明显改变;在海拔5 000 m的48 h、72 h组可见少许脑细胞水肿。海拔6 000 m构建的HACE模型最为显著,各组HE染色均出现脑细胞体积增大、肿胀,以24 h、48 h、72 h为甚,并出现细胞排列紊乱、间隙增大及核固缩;模型鉴定示海拔6 000 m构建的HACE模型小鼠脑水肿和EB通透率12 h后增加,各时点无明显细胞凋亡。结论用低压低氧舱模拟海拔6 000 m(气压47.19 kPa、氧分压9.73 kPa)可有效建立HACE模型。

关键词：高原反应高原脑水肿血脑屏障低压低氧

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：