Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the HimalayasReportar como inadecuado

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Human Genetics

, Volume 135, Issue 4, pp 393–402

First Online: 16 February 2016Received: 06 August 2015Accepted: 23 January 2016


High-altitude adaptation in Tibetans is influenced by introgression of a 32.7-kb haplotype from the Denisovans, an extinct branch of archaic humans, lying within the endothelial PAS domain protein 1 EPAS1, and has also been reported in Sherpa. We genotyped 19 variants in this genomic region in 1507 Eurasian individuals, including 1188 from Bhutan and Nepal residing at altitudes between 86 and 4550 m above sea level. Derived alleles for five SNPs characterizing the core Denisovan haplotype AGGAA were present at high frequency not only in Tibetans and Sherpa, but also among many populations from the Himalayas, showing a significant correlation with altitude Spearman’s correlation coefficient = 0.75, p value 3.9 × 10. Seven East- and South-Asian 1000 Genomes Project individuals shared the Denisovan haplotype extending beyond the 32-kb region, enabling us to refine the haplotype structure and identify a candidate regulatory variant rs370299814 that might be interacting in an additive manner with the derived G allele of rs150877473, the variant previously associated with high-altitude adaptation in Tibetans. Denisovan-derived alleles were also observed at frequencies of 3–14 % in the 1000 Genomes Project African samples. The closest African haplotype is, however, separated from the Asian high-altitude haplotype by 22 mutations whereas only three mutations, including rs150877473, separate the Asians from the Denisovan, consistent with distant shared ancestry for African and Asian haplotypes and Denisovan adaptive introgression.

S. Hackinger and T. Kraaijenbrink contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00439-016-1641-2 contains supplementary material, which is available to authorized users.

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Autor: Sophie Hackinger - Thirsa Kraaijenbrink - Yali Xue - Massimo Mezzavilla - Asan - George van Driem - Mark A. Jobling - Pete

Fuente: https://link.springer.com/

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