title: Shared and unique signals of high-altitude adaptation in geographically distinct Tibetan populations.
abstract: Recent studies have used a variety of analytical methods to identify genes targeted by selection in high-altitude populations located throughout the Tibetan Plateau. Despite differences in analytic strategies and sample location, hypoxia-related genes, including EPAS1 and EGLN1, were identified in multiple studies. By applying the same analytic methods to genome-wide SNP information used in our previous study of a Tibetan population (n = 31) from the township of Maduo, located in the northeastern corner of the Qinghai-Tibetan Plateau (4200 m), we have identified common targets of natural selection in a second geographically and linguistically distinct Tibetan population (n = 46) in the Tuo Tuo River township (4500 m). Our analyses provide evidence for natural selection based on iHS and XP-EHH signals in both populations at the p<0.02 significance level for EPAS1, EGLN1, HMOX2, and CYP17A1 and for PKLR, HFE, and HBB and HBG2, which have also been reported in other studies. We highlight differences (i.e., stratification and admixture) in the two distinct Tibetan groups examined here and report selection candidate genes common to both groups. These findings should be considered in the prioritization of selection candidate genes in future genetic studies in Tibet.
authors.affiliation: Research Center for High-Altitude Medicine, Qinghai University Medical School, Xining, Qinghai, People's Republic of China.
authors.forename: Tana
authors.initials: T
authors.lastname: Wuren
authors.affiliation: Division of Physiology, Department of Medicine, University of California San Diego, La Jolla, California, United States of America; Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Tatum S
authors.initials: TS
authors.lastname: Simonson
authors.affiliation: Research Center for High-Altitude Medicine, Qinghai University Medical School, Xining, Qinghai, People's Republic of China.
authors.forename: Ga
authors.initials: G
authors.lastname: Qin
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Chad D
authors.initials: CD
authors.lastname: Huff
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Witherspoon
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
authors.affiliation: Research Center for High-Altitude Medicine, Qinghai University Medical School, Xining, Qinghai, People's Republic of China.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000531:Altitude; D044466:Asian People; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000208:ethnology / Q000235:genetics*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D018609:Tibet; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004272:DNA, Mitochondrial; D006419:Heme Oxygenase (Decyclizing); D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D000099162:Endothelial PAS Domain-Containing Protein 1; C490190:EGLN1 protein, human; C105245:heme oxygenase-2