Title
Genetic variants at the EGLN1 locus associated with high-altitude adaptation in Tibetans are absent or found at low frequency in highland Andeans
Date Issued
01 May 2019
Access level
open access
Resource Type
journal article
Publisher(s)
Blackwell Publishing Ltd
Abstract
EGLN1 encodes the hypoxia-inducible factor (HIF) pathway prolyl hydroxylase 2 (PHD2) that serves as an oxygen-sensitive regulator of HIF activity. The EGLN1 locus exhibits a signature of positive selection in Tibetan and Andean populations and is associated with hemoglobin concentration in Tibetans. Recent reports provide evidence for functional roles of protein-coding variants within the first exon of EGLN1 (rs186996510, rs12097901) that are linked to an adaptive signal in Tibetans, yet whether these same variants are present and contribute to adaptation in Andean highlanders is unknown. We determined the frequencies of these adaptive Tibetan alleles in Quechua Andeans resident at high altitude (4,350 m) in addition to individuals of Nepali ancestry resident at sea level. The rs186996510 C (minor) allele previously found at high frequency in Tibetans is absent in Andean (G: 100%) and rare among Nepali (C: 11.8%, G: 88.2%) cohorts. The minor G allele of rs12097901 is found at similarly low frequencies in Andeans (G: 12.7%, C: 87.3%) and Nepalis (G: 23.5%, C: 76.5%) compared to Tibetans. These results suggest that adaptation involving EGLN1 in Andeans involves different mechanisms than those described in Tibetans. The precise Andean adaptive variants remain to be determined.
Start page
171
End page
176
Volume
83
Issue
3
Language
English
OCDE Knowledge area
Genética, Herencia Fisiología
Scopus EID
2-s2.0-85061052321
PubMed ID
Source
Annals of Human Genetics
ISSN of the container
00034800
Sponsor(s)
The authors thank the research team at the Instituto de Inves-tigaciones de Altura in Cerro de Pasco, Peru, for assistance with sample collection in Peru. We would also like to thank Pavan Shrestha for his assistance with recruitment of Nepali participants, Dr. Philip Bickler for the kind use of his laboratory space at the University of California, San Francisco, and Elizabeth Blue for R code. This research was further supported by resources from the Center for Physiological Genomics of Low Oxygen (CPGLO) at the University of California, San Diego, by an Investigators Programme grant from Science Foundation Ireland (12/IP/1727), and by a Wellcome Trust grant (107544/Z/15/Z) to support the UPCH team.
Sources of information: Directorio de Producción Científica Scopus