Dataset Information

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

ABSTRACT: 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 2?. 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?

SUBMITTER: Eichstaedt CA

PROVIDER: S-EPMC5638799 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Eichstaedt Christina A CA Pagani Luca L Antao Tiago T Inchley Charlotte E CE Cardona Alexia A Mörseburg Alexander A Clemente Florian J FJ Sluckin Timothy J TJ Metspalu Ene E Mitt Mario M Mägi Reedik R Hudjashov Georgi G Metspalu Mait M Mormina Maru M Jacobs Guy S GS Kivisild Toomas T

Scientific reports 20171012 1

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 be ...[more]

PMID: 29026132

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Project description:Humans living at high altitude (? 2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways that may be involved in high-altitude adaptation in Andean populations.

Dataset Information

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

Publications

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

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