title: The genetic basis of chronic mountain sickness.
abstract: Chronic mountain sickness (CMS) is a disease that affects many high-altitude dwellers, particularly in the Andean Mountains in South America. The hallmark symptom of CMS is polycythemia, which causes increased risk of pulmonary hypertension and stroke (among other symptoms). A prevailing hypothesis in high-altitude medicine is that CMS results from a population-specific "maladaptation" to the hypoxic conditions at high altitude. In contrast, the prevalence of CMS is very low in other high-altitude populations (e.g., Tibetans and Ethiopians), which are seemingly well adapted to hypoxia. In recent years, concurrent with the advent of genomic technologies, several studies have investigated the genetic basis of adaptation to altitude. These studies have identified several candidate genes that may underlie the adaptation, or maladaptation. Interestingly, some of these genes are targeted by known drugs, raising the possibility of new treatments for CMS and other ischemic diseases. We review recent discoveries, alongside the methodologies used to obtain them, and outline some of the challenges remaining in the field.
authors.affiliation: Bioinformatics & Systems Biology Graduate Program, University of California San Diego, La Jolla, California;
authors.forename: Roy
authors.initials: R
authors.lastname: Ronen
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, University of California San Diego, La Jolla, California;
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Computer Science and Engineering, University of California San Diego, La Jolla, California;
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.affiliation: Department of Pediatrics, Division of Respiratory Medicine, University of California San Diego, La Jolla, California; Department of Neurosciences, University of California San Diego, La Jolla, California; and Rady Children's Hospital, San Diego, California.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
mesh_terms: D000064:Acclimatization; D000531:Altitude; D000532:Altitude Sickness / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D005002:Ethiopia / Q000453:epidemiology; D059647:Gene-Environment Interaction; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D000860:Hypoxia / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D015995:Prevalence; D065840:Protective Factors; D012307:Risk Factors; D018609:Tibet / Q000453:epidemiology
chemical_list: D005819:Genetic Markers