Systems biology approach to study the high altitude adaptation in tibetans

Bi, Dingren; Hu, Xin; Zhou, Chunmei; Zhou, Jun; Deng, Xiaoyan; Liu, Xiaopeng

doi:10.1590/s1516-89132013000100007

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…The upregulated genes TAB2, TGFB2, MAP4K1, MINK1, ATF2, MAPT, ARRB2, MAPK3, KRAS, CDC25B, PTPN7, JUND, MAP4K3 of this particular pathway in Ladakhi cows may be associated with the high-altitude adaptation. Some of the recent studies have also shown indication of MAPK signaling pathway in high altitude adaptation especially in Tibetans 42 . Further, in recent past, relationship of this pathway with hypoxic response has also been documented 43 .…”

Section: Discussionmentioning

confidence: 96%

Transcriptome Analysis of Circulating PBMCs to Understand Mechanism of High Altitude Adaptation in Native Cattle of Ladakh Region

Verma

Sharma

Sodhi

et al. 2018

Sci Rep

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Ladakhi cattle is native population of Leh and Ladakh region and constantly exposed to hypobaric hypoxia over many generations. In present study, transcriptome signatures of cattle from Ladakh region (~5500 m) and Sahiwal cattle from tropical regions were evaluated using Agilent 44 K microarray chip. The top up-regulated genes in Ladakhi cows were INHBC, ITPRI, HECA, ABI3, GPR171, and HIF-1α involved in hypoxia and stress response. In Sahiwal cows, the top up-regulated genes eEF1A1, GRO1, CXCL2, DEFB3 and BOLA-DQA3 were associated with immune function and inflammatory response indicating their strong immune potential to combat the pathogens prevalent in the tropical conditions. The molecular pathways highly impacted were MAPK signaling, ETC, apoptosis, TLR signaling and NF- kB signaling pathway indicating signatures of adaptive evolution of these two cattle types in response to diverse environments. Further, qPCR analysis revealed increased expression of DEGs such as HIF-1, EPAS-1, VEGFA, NOS2, and GLUT-1/SLC2A1 in cattle types from high altitude suggesting their pivotal role in association with high altitude adaptation. Based on data generated, native cattle of Ladakh region was found to be genetically distinct from native cattle adapted to the tropical region of India.

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Section: Discussionmentioning

confidence: 96%

Transcriptome Analysis of Circulating PBMCs to Understand Mechanism of High Altitude Adaptation in Native Cattle of Ladakh Region

Verma

Sharma

Sodhi

et al. 2018

Sci Rep

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“…Four DE miRNAs (ssc-miR-210, ssc-miR-1343, ssc-miR-142-5p, and ssc-miR-421-5p) that are involved in the renal cell carcinoma pathway were upregulated in TPs, and the corresponding target genes were EPAS1 , EGLN3 , EGLN1 , and VEGFC . Both EPAS1 and EGLN1 are closely associated with the high-altitude adaptation of Tibetan populations [ 37 ], and are involved in hypoxia pathways as key regulators during chronic hypoxia [ 52 ]. Genetic variation in EPAS1 and EGLN1 is associated with Hb levels and high-altitude adaptation in Tibetan populations [ 36 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive MicroRNA Expression Profile Related to Hypoxia Adaptation in the Tibetan Pig

et al. 2015

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Tibetan pigs live between 2500 and 4300 m above sea level on the Tibetan Plateau, and are better adapted to hypoxia than lowland pigs. MicroRNAs (miRNAs) are involved in a wide variety of cellular processes; however, their regulatory role in hypoxia adaptation remains unclear. In this study, miRNA-seq was used to identify differentially expressed miRNAs (DE miRNAs) in the cardiac muscle of Tibetan and Yorkshire pigs, which were both raised in high elevation environments. We obtained 108 M clean reads and 372 unique miRNAs, which included 210 known porcine miRNAs, 136 conserved in other mammals, and 26 novel pre-miRNAs. In addition, 20 DE miRNAs, including 10 up-regulated and 10 down-regulated miRNAs, were also found after comparison between Tibetan and Yorkshire pigs. We predicted miRNA targets based on differential expression and abundance in the two populations. Furthermore, the results of a Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that DE miRNAs in Tibetan and Yorkshire pigs are involved in hypoxia-related signaling pathways such as the mitogen-activated protein kinase, which is the mechanistic target of rapamycin, and the vascular endothelial growth factor, as well as cancer-related signaling pathways. Five DE miRNAs were randomly selected to validate the results of miRNA-seq using real-time polymerase chain reaction, and the results corresponded to those from the miRNA-seq, confirming that deep-sequencing methods are feasible and efficient. In our study, we identified various previously unknown hypoxia-related miRNAs in pigs, and the data obtained suggest that hypoxia-related miRNA expression patterns are significantly altered in the Tibetan pig compared to other species. Therefore, DE miRNAs may play an important role in organisms that have adapted to hypoxic environments.

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“…Usually, hypoxia occurs in high-attitude and pathological conditions. Hypoxia refers to the lack of oxygen 7 , and the adaptation to hypoxia is a complex process contains biological pathways and gene networks 8 . Thereby, understanding genetic factors that underlie adaptation to high-altitude conditions could lead to a new source of knowledge in order to understand the adaptation process 9 .…”

Section: Introductionmentioning

confidence: 99%

Genomic analysis reveals variant association with high altitude adaptation in native chickens

Kharrati-Koopaee

Ebrahimie

Dadpasand

et al. 2019

Sci Rep

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Native chickens are endangered genetic resources that are kept by farmers for different purposes. Native chickens distributed in a wide range of altitudes, have developed adaptive mechanisms to deal with hypoxia. For the first time, we report variants associated with high-altitude adaptation in Iranian native chickens by whole genome sequencing of lowland and highland chickens. We found that these adaptive variants are involved in DNA repair, organs development, immune response and histone binding. Amazingly, signature selection analysis demonstrated that differential variants are adaptive in response to hypoxia and are not due to other evolutionary pressures. Cellular component analysis of variants showed that mitochondrion is the most important organelle for hypoxia adaptation. A total of 50 variants was detected in mtDNA for highland and lowland chickens. High-altitude associated with variant discovery highlighted the importance of COX3 , a gene involved in cell respiration, in hypoxia adaptation. The results of study suggest that MIR6644-2 is involved in hypoxia and high-altitude adaptations by regulation of embryo development. Finally, 3877 novel SNVs including the mtDNA ones, were submitted to EBI (PRJEB24944). Whole-genome sequencing and variant discovery of native chickens provided novel insights about adaptation mechanisms and highlights the importance of valuable genomic variants in chickens.

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Systems biology approach to study the high altitude adaptation in tibetans

Cited by 6 publications

References 35 publications

Transcriptome Analysis of Circulating PBMCs to Understand Mechanism of High Altitude Adaptation in Native Cattle of Ladakh Region

Transcriptome Analysis of Circulating PBMCs to Understand Mechanism of High Altitude Adaptation in Native Cattle of Ladakh Region

A Comprehensive MicroRNA Expression Profile Related to Hypoxia Adaptation in the Tibetan Pig

Genomic analysis reveals variant association with high altitude adaptation in native chickens

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