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Sci Rep. 2017 Oct 12;7(1):13042. doi: 10.1038/s41598-017-13382-4.

Evidence of Early-Stage Selection on EPAS1 and GPR126 Genes in Andean High Altitude Populations.

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Thoraxclinic at the University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany.
Institute of Human Genetics, Heidelberg University, Heidelberg, Baden-Württemberg, Germany.
Department of Archaeology and Anthropology, University of Cambridge, Cambridge, Cambridgeshire, UK.
Estonian Biocentre, Tartu, Tartumaa, Estonia.
Division of Biological Sciences, University of Montana, Missoula, Missoula County, Montana, USA.
MRC Epidemiology Unit, University of Cambridge, Cambridge, Cambridgeshire, UK.
Institute for Computational Biology, University of Montpellier, Montferrier-sur-Lez, Hérault, France.
Mathematical Sciences, University of Southampton, Southampton, Hampshire, UK.
Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Tartumaa, Estonia.
Estonian Genome Centre, University of Tartu, Tartu, Tartumaa, Estonia.
Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Tartumaa, Estonia.
Statistics and Bioinformatics Group, Institute of Fundamental Sciences, Massey University, Palmerston North, Kairanga, New Zealand.
Department of Applied Sciences, Faculty of Humanities and Social Sciences, University of Winchester, Winchester, Hampshire, UK.
Complexity Institute, Nanyang Technological University, Singapore, Singapore.


The aim of this study is to identify genetic variants that harbour signatures of recent positive selection and may facilitate physiological adaptations to hypobaric hypoxia. To achieve this, we conducted whole genome sequencing and lung function tests in 19 Argentinean highlanders (>3500 m) comparing them to 16 Native American lowlanders. We developed a new statistical procedure using a combination of population branch statistics (PBS) and number of segregating sites by length (nSL) to detect beneficial alleles that arose since the settlement of the Andes and are currently present in 15-50% of the population. We identified two missense variants as significant targets of selection. One of these variants, located within the GPR126 gene, has been previously associated with the forced expiratory volume/forced vital capacity ratio. The other novel missense variant mapped to the EPAS1 gene encoding the hypoxia inducible factor 2α. EPAS1 is known to be the major selection candidate gene in Tibetans. The derived allele of GPR126 is associated with lung function in our sample of highlanders (p < 0.05). These variants may contribute to the physiological adaptations to hypobaric hypoxia, possibly by altering lung function. The new statistical approach might be a useful tool to detect selected variants in population studies.

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