According to a large multinational team of researchers, two genes – the blood cell regulator SENP1 and the cancer-associated gene ANP32D – play a key role in mountain sickness, also known as Monge’s disease.

There are approximately140 million people living permanently at high altitudes, where oxygen levels are low. Many of them have adapted to their environment, but others have Monge’s disease characterized by heart attacks, strokes, and pulmonary issues at an early age.

To identify and characterize the genes that are involved in adaptation to high-altitude, low-oxygen environments, the team sequenced the entire genomes of 20 individuals living in the Andes – ten with chronic mountain sickness and ten without. The scientists identified eleven regions with significant differences between the two groups.

In these regions, two genes were expressed to a greater extent in individuals with chronic mountain sickness than in those without the condition in response to low oxygen levels.

The team also demonstrated that reducing the expression of these two genes, SENP1 and ANP32D, improved survival under low-oxygen conditions both in flies and in human cells.

“We showed that the genes that were identified by the whole-genome scan were actually linked causally to sickness in low-oxygen environments,” said Dr Gabriel Haddad of the University of California, San Diego, who is a senior author of a paper published in the American Journal of Human Genetics.

“With further study, the two genes we identified and validated may become potential drug targets for treating conditions related to low oxygen levels, such as strokes and heart attacks. In addition, they may also be considered as targets for a potential drug treatment for chronic mountain sickness,” Dr Haddad said.

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Bibliographic information: Dan Zhou et al. Whole-Genome Sequencing Uncovers the Genetic Basis of Chronic Mountain Sickness in Andean Highlanders. American Journal of Human Genetics, published online August 15, 2013; doi: 10.1016/j.ajhg.2013.07.011