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Penn researchers help solve questions about Ethiopians' high-altitude adaptations
Date:1/20/2012

able and we spent a lot of time just trying to find the groups that were living at the highest altitude possible."

The researchers compared the genotypes and phenotypes of Amhara participants with those of two other Ethiopian groups that live at lower altitudes. They also compared the Amhara group with Nigerian and European groups that live at or around sea level.

"We make these comparisons," Scheinfeldt said, "to figure out where in the genome the high-altitude group looks distinct from the other groups. Those distinct areas are candidate regions for genetic variants contributing to high altitude adaptation. Two of the top candidates are involved in the HIF-1 pathway, a pathway that is initiated in hypoxic conditions."

Both the Andean and Tibetan populations had mutations related to the HIF-1 pathway as well, but all three groups differed in both genotype and phenotype. One difference in phenotype had to do with hemoglobin, the part of the blood that transports oxygen. Ethiopians and Andeans had hemoglobin levels that were higher than low-altitude populations, but the Tibetans had average levels.

The researchers also discovered a variant in the Ethiopian groups in a gene involved in mitochondrial function. Mitochondria regulate the production of ATP, the chemical cells use for energy, making this gene another interesting candidate for playing a role in adaptation to high altitude.

These differences all seem to play a role in how well a body can maintain homeostasis in low-oxygen conditions, but even seemingly clear advantages, such as higher levels of hemoglobin, are only proxies for more complex phenotypic changes. Putting them together into the big picture of how certain genes translate into a survival advantage will require more focused research based on the Tishkoff lab's findings.

We're chipping away at this question," Scheinfeldt said. "Every little bit helps."

Such research holds promise bey
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Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

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