Tibetan <i>PHD2</i> , an allele with loss-of-function properties
Daisheng Song, Bradleigh E. Navalsky, Wei Guan, Cassandra Ingersoll, Tao Wang, Emanuele Loro, Lydia Eeles, Kyle B. Matchett, Melanie J. Percy, John Walsby-Tickle, James McCullagh, Reinhold J. Medina, Tejvir S. Khurana, Abigail W. Bigham, Terence R.J. Lappin, Frank S. Lee
Abstract
Significance Tibetans have lived for thousands of years at an altitude where oxygen concentrations are low (hypoxia). They are known to have physiologic adaptations, including increased breathing responses to low oxygen and decreased blood pressure in the lungs. Tibetans also are known to have mutations in two genes, PHD2 and HIF2A , that are central components of a molecular hypoxia response pathway. We provide evidence here that Tibetan PHD2 promotes increased breathing responses to hypoxia. The Tibetan HIF2A gene is likely to account for the decreased blood pressure in the lungs. Thus, the hypoxia response pathway has been altered in Tibetans to facilitate adaptation to the hypoxia of high altitude.