Developmental Effects Determine Submaximal Arterial Oxygen Saturation in Peruvian Quechua

Kiyamu, Melisa; León‐Velarde, Fabiola; Rivera-Chira, María; Elías, Gianpietro; Brutsaert, Tom D.

doi:10.1089/ham.2014.1126

Cited by 9 publications

(9 citation statements)

References 43 publications

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“…Peruvian Quechua born and raised at altitude display higher SaO 2 during exercise compared with Peruvian Quechua born and raised at sea level, but tested in altitude conditions ( Bigham et al. 2008 ; Kiyamu, León-Velarde, et al. 2015 ).…”

Section: Introductionmentioning

confidence: 88%

Genome-Wide Epigenetic Signatures of Adaptive Developmental Plasticity in the Andes

Childebayeva

Goodrich

León‐Velarde³

et al. 2020

Genome Biology and Evolution

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High-altitude adaptation is a classic example of natural selection operating on the human genome. Physiological and genetic adaptations have been documented in populations with a history of living at high altitude. However, the role of epigenetic gene regulation, including DNA methylation, in high-altitude adaptation is not well understood. We performed an epigenome-wide DNA methylation association study based on whole blood from 113 Peruvian Quechua with differential lifetime exposures to high altitude (>2,500) and recruited based on a migrant study design. We identified two significant differentially methylated positions (DMPs) and 62 differentially methylated regions (DMRs) associated with high-altitude developmental and lifelong exposure statuses. DMPs and DMRs were found in genes associated with hypoxia-inducible factor pathway, red blood cell production, blood pressure, and others. DMPs and DMRs associated with fractional exhaled Nitric Oxide (FeNO) also were identified. We found a significant association between EPAS1 methylation and EPAS1 SNP genotypes, suggesting that local genetic variation influences patterns of methylation. Our findings demonstrate that DNA methylation is associated with early developmental and lifelong high-altitude exposures among Peruvian Quechua as well as altitude-adaptive phenotypes. Together these findings suggest that epigenetic mechanisms might be involved in adaptive developmental plasticity to high altitude. Moreover, we show that local genetic variation is associated with DNA methylation levels, suggesting that methylation associated SNPs could be a potential avenue for research on genetic adaptation to hypoxia in Andeans.

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Section: Introductionmentioning

confidence: 88%

Genome-Wide Epigenetic Signatures of Adaptive Developmental Plasticity in the Andes

Childebayeva

Goodrich

León‐Velarde³

et al. 2020

Genome Biology and Evolution

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“…Genetic factors are also implicated insofar as Andean total lung volumes are greater than values seen in lowlanders born and raised at high altitude [ 19 ], and the proportion of indigenous American ancestry is directly related to residual volume yet, interestingly, not chest dimensions [ 20 ]. However, there appears to be an interaction between Andean ancestry and high-altitude residence that acts to increase the altitude-associated expansion of chest dimensions and lung volumes [ 19 ] and reduction in stature and limb measurements [ 21 ]. While more studies are needed with controls for confounding factors, the improved efficiency of O 2 transfer is likely important for maintaining arterial O 2 saturation and thus, blood O 2 content during exercise [ 16 , 22 ].…”

Section: Genetic Adaptation Of Andean High-altitude Populationsmentioning

confidence: 99%

Human Genetic Adaptation to High Altitude: Evidence from the Andes

Julian

Moore

2019

Genes

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Whether Andean populations are genetically adapted to high altitudes has long been of interest. Initial studies focused on physiological changes in the O2 transport system that occur with acclimatization in newcomers and their comparison with those of long-resident Andeans. These as well as more recent studies indicate that Andeans have somewhat larger lung volumes, narrower alveolar to arterial O2 gradients, slightly less hypoxic pulmonary vasoconstrictor response, greater uterine artery blood flow during pregnancy, and increased cardiac O2 utilization, which overall suggests greater efficiency of O2 transfer and utilization. More recent single nucleotide polymorphism and whole-genome sequencing studies indicate that multiple gene regions have undergone recent positive selection in Andeans. These include genes involved in the regulation of vascular control, metabolic hemostasis, and erythropoiesis. However, fundamental questions remain regarding the functional links between these adaptive genomic signals and the unique physiological attributes of highland Andeans. Well-designed physiological and genome association studies are needed to address such questions. It will be especially important to incorporate the role of epigenetic processes (i.e.; non-sequence-based features of the genome) that are vital for transcriptional responses to hypoxia and are potentially heritable across generations. In short, further exploration of the interaction among genetic, epigenetic, and environmental factors in shaping patterns of adaptation to high altitude promises to improve the understanding of the mechanisms underlying human adaptive potential and clarify its implications for human health.

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“…The clearest such one is an increase in lung volume, which raises the alveolar surface area over which O 2 diffusion can take place and acts, in turn, to narrow the alveolar to arterial O 2 gradient and improve SaO 2 , particularly during exercise (Kiyamu et al, 2015). Increases in lung volume occur universally in persons (or experimental animals) raised at high altitude, being seen in the short-term residents of Colorado (DeGraff et al, 1970; Johnson et al, 1985) as well as the multigenerational residents of the Andes or Himalayas (Droma et al, 1991; Frisancho, 1969), although some features such as chest size and shape appear specific to Andeans (Frisancho, 1983).…”

Section: Has Genetic Adaptation To High Altitude Occured?mentioning

confidence: 99%

Human genetic adaptation to high altitudes: Current status and future prospects

Moore

2017

Quaternary International

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The question of whether human populations have adapted genetically to high altitude has been of interest since studies began there in the early 1900s. Initially there was debate as to whether genetic adaptation to high altitude has taken place based, in part, on disciplinary orientation and the sources of evidence being considered. Studies centered on short-term responses, termed acclimatization, and the developmental changes occurring across lifetimes. A paradigm shift occurred with the advent of single nucleotide polymorphism (SNP) technologies and statistical methods for detecting evidence of natural selection, resulting in an exponential rise in the number of publications reporting genetic adaptation. Reviewed here are the various kinds of evidence by which adaptation to high altitude has been assessed and which have led to widespread acceptance of the idea that genetic adaptation to high altitude has occurred. While methodological and other challenges remain for determining the specific gene or genes involved and the physiological mechanisms by which they are exerting their effects, considerable progress has been realized as shown by recent studies in Tibetans, Andeans and Ethiopians. Further advances are anticipated with the advent of new statistical methods, whole-genome sequencing and other molecular techniques for finer-scale genetic mapping, and greater intradisciplinary and interdisciplinary collaboration to identify the functional consequences of the genes or gene regions implicated and the time scales involved.

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Developmental Effects Determine Submaximal Arterial Oxygen Saturation in Peruvian Quechua

Cited by 9 publications

References 43 publications

Genome-Wide Epigenetic Signatures of Adaptive Developmental Plasticity in the Andes

Genome-Wide Epigenetic Signatures of Adaptive Developmental Plasticity in the Andes

Human Genetic Adaptation to High Altitude: Evidence from the Andes

Human genetic adaptation to high altitudes: Current status and future prospects

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