RESUMEN
By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200-3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2alpha, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.
Asunto(s)
Alelos , Mal de Altura/genética , Altitud , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/fisiología , Hemoglobinas/metabolismo , Selección Genética , Variación Genética , Genoma Humano , Homocigoto , Humanos , Hipoxia , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , TibetRESUMEN
This paper focuses on assistance that externally-resident daughters provide for their aging parents in rural Tibet, China, to challenge the notion that rapid modernization invariably threatens family-based care systems for the elderly. The authors discuss social and economic changes associated with modernization that have created new opportunities for parents to send daughters out of their natal households in ways that can benefit them in old age. By investing in a daughter's education so she can secure salaried employment, or by helping a daughter establish a small business so she can earn an independent livelihood, the authors demonstrate how some externally-resident daughters represent a novel form of social capital that parents can draw on for social support. Daughters with income and freedom from extended family obligations are now providing elderly parents with (1) leverage against co-resident children who do not treat them well, (2) temporary places of refuge from ill-treatment at home, (3) caretaking services and financial support when they require hospitalization, and (4) financial resources independent of their household which they can use to pursue age-appropriate activities like pilgrimage. The authors conclude that this new form of social capital vested in externally-resident daughters is having a positive impact on the lives of the elderly in rural Tibet.