RESUMO
Genetic 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.
Assuntos
Adaptação Fisiológica/genética , DNA/genética , Hipóxia/genética , Polimorfismo Genético , Simulação por Computador , Marcadores Genéticos , Humanos , Modelos Genéticos , NepalRESUMO
In this work we demonstrate that the stress-induced reduction in bone marrow granulocyte-macrophage colonies, reported previously from our laboratory, is prevented by both the inhibition of the hypothalamic-pituitary-adrenal axis (HPAA) and the blockage of opioid receptors. The inhibition of the HPAA was obtained through the administration of dexamethasone (1 mg/kg). The blockage of opioid receptors was done in two ways, by the administration of naltrexone (8 mg/kg) and induction of tolerance to morphine. On the other hand, no protection was observed in metyrapone treated rats. We suggest that the two physiological systems, opioid and HPAA, mediate the stress-induced myelosuppression and that these systems may function independently in this particular situation.
Assuntos
Leucopoese/fisiologia , Estresse Fisiológico/fisiopatologia , Animais , Células da Medula Óssea/citologia , Dexametasona/farmacologia , Feminino , Glucocorticoides/farmacologia , Granulócitos/citologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiologia , Leucopoese/efeitos dos fármacos , Macrófagos/citologia , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiologia , Ratos , Ratos WistarRESUMO
Bone marrow cell responsiveness to hematopoietic growth factors was investigated in rats only confined or experiencing inescapable, escapable shocks or no electric shock. The results demonstrated a significant reduction in the number of granulocyte-macrophage precursors in the bone marrow of confined rats and of rats exposed to inescapable shocks. The reversibility of this mielossupressive response was seen in both groups and occurred first in the confined animals. No changes were observed in the group submitted to escapable shocks when compared to controls.