Document Detail

An evolutionary model for identifying genetic adaptation to high altitude.
MedLine Citation:
PMID:  17089883     Owner:  NLM     Status:  MEDLINE    
Coordinated maternal/fetal responses to pregnancy are required to ensure continuous O2 delivery to the developing organism. Mammals employ distinctive reproductive strategies that afford their young an improved chance of survival through the completion or the reproductive period. Thus, mortality prior to the end of the reproductive period is concentrated in the earliest phases of the lifecycle. At high altitude, fetal growth restriction reduces birth weight and likely compromises survival during the early postnatal period. Population variation in the frequency of the altitude-associated increase in intrauterine growth restriction (IUGR) demonstrates that multigenerational Tibetan and Andean high-altitude populations are protected compared with shorter duration, European or Han (Chinese) residents. This experiment of nature permits testing the hypothesis that genetic factors (a) influence susceptibility to altitude-associated IUGR, (b) act on maternal vascular adjustments to pregnancy determining uteroplacental blood flow, and (c) involve genes which regulate and/or are regulated by hypoxia-inducible factors (HIFs). Serial, studies during pregnancy as well as postpartum in Andean and European residents of high (3600 m) and low (300 m) altitude will permit evaluation of whether uteroplacental O2 delivery is lower in the European than Andean women and, if so, the physiological factors responsible. Comparisons of HIF-targeted vasoactive substances and SNPs in or near HIF-regulatory or targeted genes will permit determination of whether these regions are distinctive in the Andean population. Studies coupling genetic and genomic approaches with more traditional physiological measures may be productively employed for determining the genetic mechanisms influencing physiological adaptation to high altitude.
Lorna G Moore; Mark Shriver; Lynne Bemis; Enrique Vargas
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  588     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2006  
Date Detail:
Created Date:  2006-11-08     Completed Date:  2006-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  101-18     Citation Subset:  IM    
Colorado Center for Altitude Medicine and Physiology, Division of Emergency Medicine, USA.
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MeSH Terms
Child, Preschool
Fetal Growth Retardation / pathology
Hypoxia-Inducible Factor 1 / metabolism
Infant, Newborn
Ischemia / pathology
Middle Aged
Models, Biological
Models, Genetic*
Oxygen / metabolism
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1; 7782-44-7/Oxygen

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