Association Between Human Polymorphic DNA Markers and Hypoxia Adaptation in Sherpa Detected by a Preliminary Genome Scan

Abstract

SummaryGenetic determinants of resistance to hypobaric hypoxia in the Sherpa are still unknown. Since adaptive gene variants must still be subjected to positive selection, linkage disequilibrium between such variants and specific alleles of flanking DNA markers is expected. Following this line of reasoning, we performed a human genome scan using 998 polymorphic DNA markers in 7 unrelated Sherpa porters living in the Solu-Khumbu area. This minimalist approach succeeded in detecting 8 DNA markers showing homozygosity for the same shared allele. Analysis of additional DNA samples from 2 more Sherpa porters focused our attention on three polymorphic DNA markers (D6S1697, D14S274, D17S1795) showing homozygosity for the same shared allele in 8 out 9 tested individuals. Analysis of DNA samples from Sherpa and non-Sherpa populations of Nepal proved HW equilibrium in both populations for markers D14S274 and D17S1795, while an excess of heterozygotes was observed in the Sherpa population for marker D6S1697. A significant difference in allele frequencies for D14S274 and D17S1795 between the two populations was observed. These findings exclude the possibility that homozygosity for 3 specific loci in 8 unrelated individuals might be ascribed to inbreeding or recent genetic drift. We therefore conclude that the chromosomal segments detected by such DNA markers may include genes involved in adaptation to hypobaric hypoxia.

Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

“…The few natural selection genetics studies conducted previously have focused on specific genes hypothesised to play a role in adaptation to altitude, but none of them have found conclusive evidence of this evolutionary force [21-27]. One recent study scanned 998 genetic markers in seven Nepalese Sherpa porters and identified genomic regions that may have been involved in adaptation to altitude [28]. However, genome scans using much larger panels of genetic markers and larger sample sizes will be necessary to expand upon these very preliminary findings.…”

Work-health needs of high-altitude mountain guides (Sherpas) in Nepal – a pilot study

“…Although mental health showed a strong association with dissatisfaction in physical ability (RR 4.46, 95% CI [1.22, 16.26]), the prevalence of reported mental health problems (6%, 95% CI [3,12]) was the lowest of all health categories assessed in this study. Only one single paper was found in the literature which evaluated a mental health condition in mountain guides [7].…”

“…[1] Sherpas are famed for their exceptional powers of endurance [2][3][4] and kindly temperaments. [5] The term Sherpa has come to refer not only to members of an ethnic group, but also, in a generic sense, to Nepalese mountain guides and porters.…”

“So mortal and so strange a pang”: A tribute to Paul T. Baker

“…Sherpas, like any other population, are presumably adapted in all sorts of ways. 20 Mapping identifies genes specifically involved in oxygen physiology, showing that variation in these genes affects variation in response. But this contemporary variation of genetics of adaptability does not imply that the same genes have been affected by selection in the past.…”