title: Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes.
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.
authors.forename: Nitin
authors.initials: N
authors.lastname: Udpa
authors.forename: Roy
authors.initials: R
authors.lastname: Ronen
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Junbin
authors.initials: J
authors.lastname: Liang
authors.forename: Tsering
authors.initials: T
authors.lastname: Stobdan
authors.forename: Otto
authors.initials: O
authors.lastname: Appenzeller
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Du
authors.forename: Lixia
authors.initials: L
authors.lastname: Guo
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Wenlong
authors.initials: W
authors.lastname: Jia
authors.forename: Dandan
authors.initials: D
authors.lastname: Cao
authors.forename: Guangwu
authors.initials: G
authors.lastname: Guo
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Claydon
authors.forename: Roger
authors.initials: R
authors.lastname: Hainsworth
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gamboa
authors.forename: Mehila
authors.initials: M
authors.lastname: Zibenigus
authors.forename: Guta
authors.initials: G
authors.lastname: Zenebe
authors.forename: Jin
authors.initials: J
authors.lastname: Xue
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Frazer
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D000531:Altitude; D000818:Animals; D002888:Chromosomes, Human, Pair 19; D004330:Drosophila / Q000235:genetics; D005002:Ethiopia; D005006:Ethnicity; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D010100:Oxygen / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid
chemical_list: D010100:Oxygen