The Genetics Of Mountain Sickness
August 16, 2013

Researchers Link Two Genes To Chronic Mountain Sickness

redOrbit Staff & Wire Reports - Your Universe Online

An international team of researchers has discovered the genetic basis of chronic mountain sickness (CMS), a condition developed during prolonged exposure to high altitudes, according to research appearing in the August 15 edition of the American Journal of Human Genetics.

The condition, which is also known as “Monge's disease,” is the result of low oxygen levels and can cause severe damage to the body, including heart attacks, stroke and early-onset pulmonary issues.

Now, researchers have studied the DNA of Andean residents in an attempt to discover the genetic mutations associated with CMS. For the study, a total of 20 Andean individuals had their DNA sequenced. Ten of those participants had CMS and 10 were control subjects and did not suffer from the condition.

Following a high-efficiency survey of the entire spectrum of genetic variations, the investigators discovered 11 regions which demonstrated significant differences in haplotype frequencies consistent with selective sweeps. In those regions, the researchers located two genes – ANP32D and SENP1 – that were found to have significantly increased expression in CMS individuals when compared to their non-CMS counterparts.

Those genes were found to play an essential role in tolerance to hypoxia, a pathological condition in which the entire body or a specific part of it is deprived of adequate oxygen supply. The information will also help experts better understand the mechanisms behind human adaptation to hypoxia, the researchers said.

“They speculated that the increased expression of SENP1 may play a role in the basic pathogenesis of polycythemia in CMS individuals,” the Beijing Genomics Institute (BGI), which was one of the institutions involved in the research, said in a statement. “ANP32D acts as an oncogene, which may alter cellular metabolism in a fashion that is similar to that of cancer cells, especially given that such cells can flourish in low oxygen conditions.”

“We showed that the genes that were identified by the whole-genome scan were actually linked causally to sickness in low-oxygen environments,” added co-senior author Dr. Gabriel Haddad of the University of California, San Diego. “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.”

Going forward, the authors said they will look to complete whole genome sequencing for the nearly 100 remaining patient samples in the hopes they can locate biomarkers that can be used to predict CMS. In addition, they retrieved skin samples from the study participants. Those cells could be reprogrammed into induced pluripotent stem cells that could ultimately be used to test resilience to low oxygen levels.