Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes

Udpa, Nitin, Ronen, Roy, Zhou, Dan, Liang, Junbin, Stobdan, Tsering, Appenzeller, Otto, Yin, Ye, Du, Yuanping, Guo, Lixia, Cao, Rui, Wang, Yu, Jin, Xin, Huang, Chen, Jia, Wenlong, Cao, Dandan, Guo, Guangwu, Claydon, Victoria E., Hainsworth, Roger, Gamboa, Jorge L., Zibenigus, Mehila, Zenebe, Guta, Xue, Jin, Liu, Siqi, Frazer, Kelly A., Li, Yingrui, Bafna, Vineet and Haddad, Gabriel G. (2014) Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes. Genome Biology, 15 R36: . doi:10.1186/gb-2014-15-2-r36

Author Udpa, Nitin
Ronen, Roy
Zhou, Dan
Liang, Junbin
Stobdan, Tsering
Appenzeller, Otto
Yin, Ye
Du, Yuanping
Guo, Lixia
Cao, Rui
Wang, Yu
Jin, Xin
Huang, Chen
Jia, Wenlong
Cao, Dandan
Guo, Guangwu
Claydon, Victoria E.
Hainsworth, Roger
Gamboa, Jorge L.
Zibenigus, Mehila
Zenebe, Guta
Xue, Jin
Liu, Siqi
Frazer, Kelly A.
Li, Yingrui
Bafna, Vineet
Haddad, Gabriel G.
Title Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
Publication date 2014-02-20
Year available 2014
Sub-type Article (original research)
DOI 10.1186/gb-2014-15-2-r36
Open Access Status DOI
Volume 15
Issue R36
Total pages 14
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: 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.
Results: 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-AHα, an ortholog of human PAFAH1B3.
Conclusions: 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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