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. 2012 Jan 20;13(1):R1.
doi: 10.1186/gb-2012-13-1-r1.

Genetic adaptation to high altitude in the Ethiopian highlands

Laura B Scheinfeldt  1 , Sameer Soi, Simon Thompson, Alessia Ranciaro, Dawit Woldemeskel, William Beggs, Charla Lambert, Joseph P Jarvis, Dawit Abate, Gurja Belay, Sarah A Tishkoff
Affiliations

Genetic adaptation to high altitude in the Ethiopian highlands

Laura B Scheinfeldt et al. Genome Biol. .

Abstract

Background: Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude.

Results: We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels.

Conclusions: We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.

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Figures

Figure 1
Figure 1
Principal components analysis of Amhara, Aari and Hamer individuals. Principal component (PC)1 (x-axis) versus PC2 (y axis). The Amhara are displayed in green, the Aari in orange, and the Hamer in magenta.
Figure 2
Figure 2
Genome-wide distribution of LSBL values. The chromosomes are plotted along the x-axis, and the LSBL values are plotted along the y-axis. Chromosomes are colored alternately in dark blue and light blue, and the 99.9% percentile is denoted with a dashed red line. The top candidate gene SNPs are circled in red and the gene names are labeled above.
Figure 3
Figure 3
Boxplot of hemoglobin levels estimated in the Amhara, Aari and Hamer population samples. Each population sample along with the altitude in meters at which the sample was collected is shown on the x-axis, and the hemoglobin (Hb) levels are plotted on the y-axis.
See this image and copyright information in PMC

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