Gene Expression Profiling of High Altitude Polycythemia in Han Chinese migrated to Qinghai-Tibetan Plateau
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29977 | GEO | 2014/06/15
SECONDARY ACCESSION(S): PRJNA140863
REPOSITORIES: GEO
Similar Datasets
Project description:Long term-exposed to high altitude, the increased numbers of red blood cells tend to stabilize to a certain extend in most people, but someone will occur over-increasing in number of red blood cells, which cause a serious of clinical symptoms and signs, and this is high altitude polycythemia. EPO-EPOR system may be the main reasons for erythroid progenitor cell proliferation and differentiation in early exposion to plateau, but, in the late, there may be other factors involved in the regulation of erythropoiesis in bone marrow, multiple factors working together lead to excessive red blood cell proliferation. We compared gene expression profiling of leukocytes in peripheral blood from high altitude polycythemia patients with those from matched controls. Subjects consisting of 5 masculine Han Chinese patients with HAPC (diagnosed according to international consensus statement on HAPC) and 5 matched controls, were migrants at River of TUOTUO area (Qinghai-Tibetan Plateau, 4550 m). Each of the five HAPC patients was matched to each of the control: gender, nationality, birthplace, duration migrating to plateau, height of location, work intensity. Peripheral blood samples were obtained at 4550m plateau from above subjects. Total RNA was extracted from peripheral blood leucocytes. The gene expression profilings were analysed by Human Genome U133 Plus 2.0 Array.
2014-06-15 | E-GEOD-29977 | biostudies-arrayexpress
Project description:Tibetan's adaptation to high-altitude environment at the Qinghai-Tibetan plateau represents a remarkable case of natural selection during recent human evolution. We generated time series paired RNAseq, ATACseq and Hi-C data in Tibetan and Han Chinese's umbilical endothelial cells from normoxia to hypoxia condition. Our results provide a broad resource of genome-wide hypoxia regulatory network to characterize the effect of genetic variation in high-altitude adaptation, and indicates large-scale maps of variants need proper cell types to understand its act on gene regulation.
2020-07-15 | GSE145774 | GEO
Project description:Background: Responses to hypoxia have been investigated in many species; however, comparative study between conspecific geographical populations in different altitude regions is rare, especially for invertebrates . The migratory locust, Locusta migratoria, is widely distributed both on high-altitude Tibetan Plateau (TP) and on low-altitude North China Plain (NP). TP locusts have inhabited Tibetan Plateau since Quaternary glaciations events and thus probably have evolved superior capacity to deal with hypoxia. Results: Here we compared the hypoxic responses of TP and NP locusts from morphological, behavioral and physiological perspectives. We found that TP locusts were more tolerant of extreme hypoxia than NP locusts, with a lower proportion exhibiting stupor, a faster recovery time, and higher respiration rates. We compared the transcriptional profiles of field TP and NP locusts and found that their differences were possibly attributed to a combination of multiple factors, e.g. oxygen, UV radiation, temperature and nutrition. To evaluate why TP locusts respond to extreme hypoxia differently from NP locusts, we subjected them to extreme hypoxia and compared their transcriptional responses. We found that the aerobic metabolism was more active in TP locusts than in NP locusts. RNAi disruption of PDHE1b, an entry gene from glycolysis to TCA cycle, increased the ratio of stupor in Tibetan locusts and decreased the ATP content of Tibetan locusts in hypoxia, confirming the significant importance of this metabolic branch for TP locusts to conquer hypoxia. Conclusions: Here we show that TP locusts are better tolerant of hypoxia than NP locusts and the better capacity to modulate primary metabolism in TP locusts contributes to their superior tolerance of hypoxia compared to NP locusts. FIELD POPULATION: TP locusts vs. NP locusts;direct comparison on 6 separate microarrays; each microarray compares one biological replicate; each biological replicate contains 10 individuals. LAB POPULATION: hypoxia-treated TP locusts vs TP locusts in normoxia; hypoxia-treated NP locusts vs NP locusts in normoxia; direct comparison on 6 separate microarrays; each microarray compares one biological replicate; each biological replicate contains 10 individuals.
2013-12-24 | E-GEOD-43327 | biostudies-arrayexpress
Project description:Background: Responses to hypoxia have been investigated in many species; however, comparative study between conspecific geographical populations in different altitude regions is rare, especially for invertebrates . The migratory locust, Locusta migratoria, is widely distributed both on high-altitude Tibetan Plateau (TP) and on low-altitude North China Plain (NP). TP locusts have inhabited Tibetan Plateau since Quaternary glaciations events and thus probably have evolved superior capacity to deal with hypoxia. Results: Here we compared the hypoxic responses of TP and NP locusts from morphological, behavioral and physiological perspectives. We found that TP locusts were more tolerant of extreme hypoxia than NP locusts, with a lower proportion exhibiting stupor, a faster recovery time, and higher respiration rates. We compared the transcriptional profiles of field TP and NP locusts and found that their differences were possibly attributed to a combination of multiple factors, e.g. oxygen, UV radiation, temperature and nutrition. To evaluate why TP locusts respond to extreme hypoxia differently from NP locusts, we subjected them to extreme hypoxia and compared their transcriptional responses. We found that the aerobic metabolism was more active in TP locusts than in NP locusts. RNAi disruption of PDHE1b, an entry gene from glycolysis to TCA cycle, increased the ratio of stupor in Tibetan locusts and decreased the ATP content of Tibetan locusts in hypoxia, confirming the significant importance of this metabolic branch for TP locusts to conquer hypoxia. Conclusions: Here we show that TP locusts are better tolerant of hypoxia than NP locusts and the better capacity to modulate primary metabolism in TP locusts contributes to their superior tolerance of hypoxia compared to NP locusts.
2013-12-24 | GSE43327 | GEO
Project description:This data was used to identify regions of the genome that have undergone positive selection in a high-altitude Tibetan population. Affymetrix SNP arrays were used to genotype DNA extracted from blood samples. This data was used to perform genome-wide scans of positive selection in a native high-altitude Tibetan population.
2010-07-22 | E-GEOD-21661 | biostudies-arrayexpress
Project description:BackgroundGiven their geographical proximity but differences in cultural and religious dietary customs, we hypothesize that children from the three main ethnic populations (Han, Hui, and Tibetan) residing in the Qinghai-Tibetan Plateau region differs in their non-iatrogenic antibiotic loads.MethodsTo determine the antibiotic burden of the school children unrelated to medical treatment, we quantified the antibiotic residues in morning urine samples from 92 Han, 72 Tibetan, and 85 Muslim Hui primary school children aged 8 to 12 years using high-performance liquid chromatography-tandem mass spectrometry, and performed correlation analysis between these data and concurrent dietary nutrition assessments.ResultsSixteen of the 18 targeted antibiotics (4 macrolides, 3 β-lactams, 2 tetracyclines, 4 quinolones, 3 sulfonamides, and 2 aminoanols) were identified in the urine samples with an overall detection frequency of 58.63%. The detection frequency of the six antibiotic classes ranged from 1.61% to 32.53% with ofloxacin showing the single highest frequency (18.47%). Paired comparison analysis revealed significant differences in antibiotic distribution frequency among groups, with Tibetans having higher enrofloxacin (P = 0.015) and oxytetracycline (P = 0.021) than Han children. Norfloxacin (a human/veterinary antibiotic) was significantly higher in the Hui children than in the Han children (P = 0.024). Dietary nutrient intake assessments were comparable among participants, showing adequate levels of essential vitamins and minerals across all three ethnic groups. However, significant differences in specific foods were observed among groups, notably in lower fat consumption in the Hui group.ConclusionsThe introduction and accumulation of antibiotic residues in school children through non-iatrogenic routes (food or environmental sources) poses a serious potential health risk and merits closer scrutiny to determine the sources. While the exact sources of misused or overused antibiotics remains unclear, further study can potentially correlate ethnicity-specific dietary practices with the sources of contamination.
| S-EPMC7039500 | biostudies-literature
Project description:Genetic and limited palaeoanthropological data suggest that Denisovans, a sister group to Neanderthals, were once widely distributed in eastern Eurasia, likely stretching from high-latitude Siberia, to the high-altitude Tibetan Plateau, to the low-latitude subtropical regions of southeast Asia. This suggests that Denisovans were capable of adapting to a highly diverse range of environments, but archaeological evidence for this is currently limited. As a result, we know little about their behaviours, including subsistence strategies, across the vast areas they likely occupied. Here, we describe the late Middle to Late Pleistocene faunal assemblage from Baishiya Karst Cave on the Tibetan Plateau, where the Xiahe Denisovan mandible and Denisovan sedimentary mtDNA were found, by integrating proteomic screening into traditional zooarchaeological analysis. The results indicate that the faunal assemblage consists of a diverse range of animals, including megafauna, large mammals, small mammals and birds, but is dominated by medium-sized herbivores. Frequent cut marks and percussion traces on bone surfaces throughout the assemblage, even on carnivore bones, indicate that Denisovan activities in Baishiya Karst Cave from at least 190 to 30 thousand years are responsible for the fauna assemblage accumulation. Thorough utilization of acquired animal resources, even perhaps the fur, too, might have helped Denisovans to survive through the last two glacial-interglacial cycles on the cold high-altitude Tibetan Plateau. Our results shed new light on Denisovan behaviours and their adaptations to the diverse and fluctuated environments in the Middle and Late Pleistocene eastern Eurasia.
2024-05-22 | PXD041874 | Pride
Project description:Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic option in high-risk ALL.
2016-02-01 | GSE76061 | GEO
Project description:The YPEL family genes are highly conserved across a diverse range of eukaryotic organisms and thus potentially involved in essential cellular processes. Ypel4, one of five YPEL family gene orthologs in mouse and human, is highly and specifically expressed in late terminal erythroid differentiation. In this study, we investigated the role of Ypel4 in murine erythropoiesis, providing for the first time an in-depth description of a Ypel4-null phenotype in vivo. We demonstrated that the Ypel4-null mice displayed a secondary polycythemia with macro- and reticulocytosis. While lack of Ypel4 did not affect steady-state erythropoiesis in the bone marrow or spleen, the anemia-recovering capacity of Ypel4-null cells was diminished. Furthermore, Ypel4-null red blood cells (RBC) were cleared from the circulation at an increased rate, demonstrating an intrinsic defect of RBCs. Scanning electron micrographs revealed an ovalocytic morphology of Ypel4-null RBCs and functional testing confirmed reduced deformability. Even though Band 3 protein levels were shown to be reduced in Ypel4-null RBC membranes, we could not find support for a physical interaction between YPEL4 and the Band 3 protein. In conclusion, our findings provide crucial insights into the role of Ypel4 in preserving normal red cell membrane functionality.
2021-08-11 | GSE171959 | GEO
Project description:High altitude polycythemia (HAPC) refers to the long-term living in the plateau of the hypoxia environment is not accustomed to cause red blood cell hyperplasia. The pathological changes are mainly the various organs and tissue congestion, blood stasis and hypoxia damage. Although chronic hypoxia is the main cause of HAPC, the related molecular mechanisms remain largely unclear. This study aims to explore the genetic basis of HAPC in the Chinese Han and Tibetan populations. We enrolled 100 patients (70 Han, 30 Tibetan) with HAPC and 100 healthy control subjects (30 Han, 70 Tibetan). To explore the hereditary basis of HAPC and investigate the association between EPHA2 with AGT and HAPC in Chinese Han and Tibetan populations. Using the Chi-squared test and analyses of genetic models, rs2291804, rs2291805, rs3768294, rs3754334, rs6603856, rs6669624, rs11260742, rs13375644 and rs10907223 in EPHA2, and rs699, rs4762 and rs5051 in AGT showed associations with reduced HAPC susceptibility in Han populations. Additionally, in Tibetan populations, rs2478523 in AGT showed an increased the risk of HAPC. Our study suggest that polymorphisms in the EPHA2 and AGT correlate with susceptibility to HAPC in Chinese Han and Tibetan populations.
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