Plasma hepcidin of Ethiopian highlanders with steady-state hypoxia.
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ABSTRACT:
SUBMITTER: Lundgrin EL
PROVIDER: S-EPMC3772503 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Plasma hepcidin of Ethiopian highlanders with steady-state hypoxia.
Lundgrin Erika L EL Janocha Allison J AJ Koch Carl D CD Gebremedhin Amha A Di Rienzo Anna A Alkorta-Aranburu Gorka G Brittenham Gary M GM Erzurum Serpil C SC Beall Cynthia M CM
Blood 20130901 11
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Project description:Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome, interpretation of the results was limited.We report here the results of the first whole genome resequencing-based analysis identifying genes that likely modulate high altitude adaptation in native Ethiopians residing at 3,500 m above sea level on Bale Plateau or Chennek field in Ethiopia. Using cross-population tests of selection, we identify regions with a significant loss of diversity, indicative of a selective sweep. We focus on a 208 kbp gene-rich region on chromosome 19, which is significant in both of the Ethiopian subpopulations sampled. This region contains eight protein-coding genes and spans 135 SNPs. To elucidate its potential role in hypoxia tolerance, we experimentally tested whether individual genes from the region affect hypoxia tolerance in Drosophila. Three genes significantly impact survival rates in low oxygen: cic, an ortholog of human CIC, Hsl, an ortholog of human LIPE, and Paf-AH?, an ortholog of human PAFAH1B3.Our study reveals evolutionarily conserved genes that modulate hypoxia tolerance. In addition, we show that many of our results would likely be unattainable using data from exome sequencing or microarray studies. This highlights the importance of whole genome sequencing for investigating adaptation by natural selection.
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Project description:Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes
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Project description:High-altitude adaptation is a remarkable example of natural selection, yet the genomic and physiological adaptation mechanisms of Ethiopian highlanders remain poorly understood compared to their Andean and Tibetan counterparts. Ethiopian populations, such as the Amhara and Oromo, exhibit unique adaptive strategies characterized by moderate hemoglobin levels and enhanced arterial oxygen saturation, indicating distinct mechanisms of coping with chronic hypoxia. This review synthesizes current genomic insights into Ethiopian high-altitude adaptation, identifying key candidate genes involved in hypoxia tolerance and examining the influence of genetic diversity and historical admixture on adaptive responses. Furthermore, the review highlights significant research gaps, particularly the underrepresentation of Ethiopian populations in global genomic studies, the lack of comprehensive genotype-phenotype analyses, and inconsistencies in research methodologies. Addressing these gaps is crucial for advancing our understanding of the genetic basis of human adaptation to extreme environments and for developing a more complete picture of human physiological resilience. This review offers a comparative perspective with Tibetan and Andean highlanders, emphasizing the need for expanding genomic representation and refining methodologies to uncover the genetic mechanisms underlying high-altitude adaptation in Ethiopian populations.
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Project description:<p>Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome (either exons or a subset of SNPs) or a group of candidate genes, interpretation of the results was limited.</p> <p>We focused our study on Ethiopian highlander populations, which have been found to be well adapted to high altitudes (~3500m). We sequenced and analyze the genomes of 13 high altitude native Ethiopians: 6 individuals of Oromo heritage living on Bale Plateau (labeled "Oromos"), and 7 individuals residing on the Chennek field in the Simien Mountains (labeled "Amhara").</p> <p>Our study revealed evolutionarily conserved genes that modulate hypoxia tolerance.</p>
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