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  Dna methylation changes are associated with an incremental ascent to high altitude

Childebayeva, A., Harman, T., Weinstein, J., Goodrich, J. M., Dolinoy, D. C., Day, T. A., et al. (2019). Dna methylation changes are associated with an incremental ascent to high altitude. Frontiers in Genetics, 10(OCT): 1062, pp. 1-10. doi:10.3389/fgene.2019.01062.

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 Creators:
Childebayeva, Ainash1, Author              
Harman, Taylor, Author
Weinstein, Julien, Author
Goodrich, Jaclyn M., Author
Dolinoy, Dana C., Author
Day, Trevor A., Author
Bigham, Abigail W., Author
Brutsaert, Tom D., Author
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1Archaeogenetics, Max Planck Institute for the Science of Human History, Max Planck Society, ou_2074310              

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Free keywords: altitude, epigenetics, DNA methylation, hypoxia, incremental ascent
 Abstract: Genetic and nongenetic factors are involved in the individual ability to physiologically acclimatize to high-altitude hypoxia through processes that include increased heart rate and ventilation. High-altitude acclimatization is thought to have a genetic component, yet it is unclear if other factors, such as epigenetic gene regulation, are involved in acclimatization to high-altitude hypoxia in nonacclimatized individuals. We collected saliva samples from a group of healthy adults of European ancestry (n = 21) in Kathmandu (1,400 m; baseline) and three altitudes during a trek to the Everest Base Camp: Namche (3,440 m; day 3), Pheriche (4,240 m; day 7), and Gorak Shep (5,160 m; day 10). We used quantitative bisulfite pyrosequencing to determine changes in DNA methylation, a well-studied epigenetic marker, in LINE-1, EPAS1, EPO, PPARa, and RXRa. We found significantly lower DNA methylation between baseline (1,400 m) and high altitudes in LINE-1, EPO (at 4,240 m only), and RXRa. We found increased methylation in EPAS1 (at 4,240 m only) and PPARa. We also found positive associations between EPO methylation and systolic blood pressure and RXRa methylation and hemoglobin. Our results show that incremental exposure to hypoxia can affect the epigenome. Changes to the epigenome, in turn, could underlie the process of altitude acclimatization. © 2019 Childebayeva, Harman, Weinstein, Goodrich, Dolinoy, Day, Bigham and Brutsaert.

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Language(s): eng - English
 Dates: 2019-10-29
 Publication Status: Published online
 Pages: 10
 Publishing info: -
 Table of Contents: Introduction

Materials and methods
- Ethics and Participant Recruitment
- Ascent Profile and Data Collection
- DNA Methylation
- Statistical Analysis

Results
- Hypoxic Exposure Is Associated With Changes in DNA Methylation
- Associations Between DNA Methylation and Phenotypic Data

Discussion
 Rev. Type: Peer
 Identifiers: DOI: 10.3389/fgene.2019.01062
Other: shh2456
 Degree: -

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Title: Frontiers in Genetics
Source Genre: Journal
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Publ. Info: Lausanne : Frontiers Media
Pages: - Volume / Issue: 10 (OCT) Sequence Number: 1062 Start / End Page: 1 - 10 Identifier: ISSN: 1664-8021
CoNE: https://pure.mpg.de/cone/journals/resource/1664-8021