Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge’s disease

Abstract

Azad and collaborators propose that Senp1 drives excessive erythropoiesis in high-altitude Andean dwellers suffering from chronic mountain sickness.

Novel insight into the genetic basis of high-altitude pulmonary hypertension in Kyrgyz highlanders

“…We note that although our sample size is limited, we have access to whole-genome sequence covering all variants (40.3× coverage) to perform selection scan on 66 haplotypes to reduce the number of loci for statistical test for association. By utilizing a pipeline that identifies regions under positive selection through an analysis of all variants in large ( > 50 kb) segments, and an integrated statistical test, we have been successful in the past identifying candidate genes involved in HA adaptations both in Ethiopian and Andean populations and these were subsequently validated [6,7,10,11]. We use a similar approach here, with some modifications (Methods).…”

Mitochondrial dysfunction in iPSC-derived neurons of subjects with chronic mountain sickness

“…And 3) are the changes observed in CMS cells as a result of hypoxia, inherent properties of the cells, or other types of stresses of high altitude? To address such questions, we should highlight the context and background of the research that we have undertaken for the past several years (2,3,18,29,32,36,37,42,48,50,51). In particular, we have done a large number of whole genome sequencing on high-altitude dwellers to investigate genetic differences between CMS and non-CMS (32,51).…”

Human and Hummingbird Hemoglobin Concentrations and MetabolicRhythms at Altitude Determined with Statistical Modeling

“…Although hummingbird species living at higher altitudes are generally heavier than their lowland relatives, there is extensive overlap among constituent species in highland and lowland communities. By contrast humans, lifelong exposure to altitude requires considerable metabolic adjustments [4,6,8], aided by steeper altitude related increases in blood hemoglobin content in Highlanders and generally smaller stature than lowlanders.…”

“…For example in the high Andes the natives often suffer from chronic mountain sickness (CMS) or Monge's disease. Such patients have very high hematocrits (hemoglobin), pulmonary hypertension, and eventually, right heart failure that causes their early demise [4,6]. By contrast, this disease is rare in the Himalayas and has not been found in natives of the East African high altitude plateau [5] suggesting genetic underpinning for human long-term altitude survival.…”

“…More than 2 million people are born, live, work and adapt to altitude in the Andes, East African high altitude plateau, and Himalayas but they cope with the ambient stress of altitude life in different ways and with varying success Claydon, et al [5]; one way to adapt to altitude is by increasing the hemoglobin content of the blood to improve oxygen uptake and delivery to tissue [6]. Additional short-term adaptive mechanisms depend on changes in (ANS) function (ANSf) such as thermoregulation and respiratory function [3].…”