The Genomics and Genetics of Oxygen Homeostasis.

Human survival is dependent upon the continuous delivery of O2 to each cell in the body in sufficient amounts to meet metabolic requirements, primarily for ATP generation by oxidative phosphorylation. Hypoxia-inducible factors (HIFs) regulate the transcription of thousands of genes to balance O2 supply and demand. The HIFs are negatively regulated by O2-dependent hydroxylation and ubiquitination by prolyl hydroxylase domain (PHD) proteins and the von Hippel-Lindau (VHL) protein. Germline mutations in the genes encoding VHL, HIF-2α, and PHD2 cause hereditary erythrocytosis, which is characterized by polycythemia and pulmonary hypertension and is caused by increased HIF activity. Evolutionary adaptation to life at high altitude is associated with unique genetic variants in the genes encoding HIF-2α and PHD2 that blunt the erythropoietic and pulmonary vascular responses to hypoxia. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 21 is August 31, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

• Publication year

  2020

• Venue

  Annual review of genomics and human genetics (Print)

• Publication date

  2020-04-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1146/annurev-genom-111119-073356PMID 32255719
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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