Genetic adaptation for high altitudes identified


Share post:

Research led by scientists from the University of California, San Diego has decoded the genetic basis of chronic mountain sickness (CMS) or Monge’s disease. Their study provides important information that validates the genetic basis of adaptation to high altitudes, and provides potential targets for CMS treatment. It has been published online in the American Journal of Human Genetics.

Genetic adaptation for high altitudes identified
Machu Picchu, Peru [Credit: WikiCommons]

More than 140 million people have permanently settled on high-altitude regions, on continents ranging from African and Asia to South America. The low-oxygen conditions at such high altitudes present a challenge for survival, and these geographically distinct populations have adapted to cope with hypoxia, or low levels of oxygen in the blood.

Interestingly, many humans living at high elevations, particularly in the Andes mountain region of South America, are maladapted and suffer CMS. The disease is characterized by an array of neurologic symptoms, including headache, fatigue, sleepiness and depression. Often, people with CMS suffer from strokes or heart attacks in early adulthood because of increased blood viscosity (resistance to blood flow that can result in decreased oxygen delivery to organs and tissues). Past studies of various populations show that CMS is common in Andeans, occasionally found in Tibetans and absent from Ethiopians living on the East African high-altitude plateau.

Therefore, the researchers dissected the genetic mechanisms underlying high-altitude adaptation by comparing genetic variation between Peruvian individuals from the Andes region with CMS and adapted subjects without CMS, using whole genome sequencing.

They identified two genes, ANP32D and SENP1, with significantly increased expression in the CMS individuals when compared to the non-CMS individuals, and hypothesized that down-regulating these genes could be beneficial in coping with hypoxia.

“While a number of published articles have described an association between certain genes and the ability for humans to withstand low oxygen at high levels, it was very hard to be sure if the association was causal,” said principal investigator Gabriel G. Haddad, Distinguished Professor and chair of the Department of Pediatrics at UC San Diego School of Medicine, and Physician-in-Chief and Chief Scientific Officer at Rady Children’s Hospital-San Diego, a research affiliate of UC San Diego.

The researchers therefore looked at genetic orthologs – corresponding gene sequences from another species, in this case the fruit fly – to assess the impact of observed genetic changes on function under conditions of hypoxia.

“We found that flies with these genes down-regulated had a remarkably enhanced survival rate under hypoxia,” said Haddad.

According to the scientists, their findings have important implications – not only for those who live at high altitudes, but also in treating certain cardiovascular and brain diseases related to low oxygen levels in individuals living at any altitude.

Next steps include whole genome sequencing for the almost 100 remaining patient samples to test if biomarkers exist to predict CMS. The researchers also retrieved skin samples from these individuals, which can be reprogramed into induced pluripotent stem cells. These IPS cells, with the capacity to become glia or red blood cells, could be used to test resilience to low oxygen levels.

Source: University of California, San Diego Health Sciences [August 15, 2013]



Related articles

Roman-era shipwrecks found in deep waters off Greece

Two Roman-era shipwrecks have been found in deep water off a western Greek island, challenging the conventional theory...

Astronomers probe inner region of young star and its planets

Astronomers have probed deeper than before into a planetary system 130 light-years from Earth. The observations mark the...

Researchers create billion-year-old bacteria and trace its evolution

University of Waikato researchers have managed to create a billion-year-old bacterial enzyme and then trace its evolution through...

Students unearth a 2,000 year old Jewish settlement near Bet Shemesh

Some 240 eleventh-grade students from Jerusalem’s Boyer High School have discovered an original and rewarding way of reducing...

First fossils of four-winged birds identified

Recent discoveries of large leg feathers in some theropods have implications for our understanding of the evolution of...

New insights into the relationship between erosion and tectonics in the Himalayas

Earth's climate interacts with so called surface processes -- such as landslides or river erosion -- and tectonics...

Another neglected monument of the Mughal era in Pakistan

About 315-year-old Mughal-era national heritage monument, the tomb of Khan-e-Jahan Bahadur Zafar Jang Kokaltash, is a picture of...

Climate change threatens tropical birds

Climate change spells trouble for many tropical birds – especially those living in mountains, coastal forests and relatively...