PMID- 25873470
OWN - NLM
STAT- MEDLINE
DCOM- 20160405
LR  - 20240324
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 6
DP  - 2015 Apr 15
TI  - Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary 
      hypertension.
PG  - 6863
LID - 10.1038/ncomms7863 [doi]
LID - 6863
AB  - High-altitude pulmonary hypertension (HAPH) has heritable features and is a major 
      cause of death in cattle in the Rocky Mountains, USA. Although multiple genes are 
      likely involved in the genesis of HAPH, to date no major gene variant has been 
      identified. Using whole-exome sequencing, we report the high association of an 
      EPAS1 (HIF2alpha) double variant in the oxygen degradation domain of EPAS1 in Angus 
      cattle with HAPH, mean pulmonary artery pressure >50 mm Hg in two independent 
      herds. Expression analysis shows upregulation of 26 of 27 HIF2alpha target genes in 
      EPAS1 carriers with HAPH. Of interest, this variant appears to be prevalent in 
      lowland cattle, in which 41% of a herd of 32 are carriers, but the variant may 
      only have a phenotype when the animal is hypoxemic at altitude. The EPAS1 variant 
      will be a tool to determine the cells and signalling pathways leading to HAPH.
FAU - Newman, John H
AU  - Newman JH
AD  - Department of Medicine, Division of Allergy, Pulmonary and Critical Care, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
FAU - Holt, Timothy N
AU  - Holt TN
AD  - Department of Veterinary Sciences, College of Agricultural Science, Colorado 
      State University, Ft Collins, Colorado 80523, USA.
FAU - Cogan, Joy D
AU  - Cogan JD
AD  - Department of Pediatrics, Division of Medical Genetics and Genomic Medicine, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
FAU - Womack, Bethany
AU  - Womack B
AD  - Department of Pediatrics, Division of Medical Genetics and Genomic Medicine, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
FAU - Phillips, John A 3rd
AU  - Phillips JA 3rd
AD  - Department of Pediatrics, Division of Medical Genetics and Genomic Medicine, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
FAU - Li, Chun
AU  - Li C
AD  - Department of Epidemiology and Biostatistics, Case Western Reserve University, 
      Cleveland, Ohio 44106, USA.
FAU - Kendall, Zachary
AU  - Kendall Z
AD  - Department of Pediatrics, Division of Medical Genetics and Genomic Medicine, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
FAU - Stenmark, Kurt R
AU  - Stenmark KR
AD  - Cardiovascular Pulmonary Research Laboratory, Department of Medicine and 
      Pediatrics, University of Colorado, Denver Colorado 80045, USA.
FAU - Thomas, Milton G
AU  - Thomas MG
AD  - Department of Animal Science, Colorado State University, Ft Collins, Colorado 
      80523, USA.
FAU - Brown, R Dale
AU  - Brown RD
AD  - Cardiovascular Pulmonary Research Laboratory, Department of Medicine and 
      Pediatrics, University of Colorado, Denver Colorado 80045, USA.
FAU - Riddle, Suzette R
AU  - Riddle SR
AD  - Cardiovascular Pulmonary Research Laboratory, Department of Medicine and 
      Pediatrics, University of Colorado, Denver Colorado 80045, USA.
FAU - West, James D
AU  - West JD
AD  - Department of Medicine, Division of Allergy, Pulmonary and Critical Care, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
FAU - Hamid, Rizwan
AU  - Hamid R
AD  - Department of Pediatrics, Division of Medical Genetics and Genomic Medicine, 
      Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
LA  - eng
GR  - R01HL102020-01/HL/NHLBI NIH HHS/United States
GR  - R01 HL102020/HL/NHLBI NIH HHS/United States
GR  - R01 HL125827/HL/NHLBI NIH HHS/United States
GR  - U01 HG007674/HG/NHGRI NIH HHS/United States
GR  - HL014985/HL/NHLBI NIH HHS/United States
GR  - P01 HL014985/HL/NHLBI NIH HHS/United States
GR  - R01 HL114887/HL/NHLBI NIH HHS/United States
GR  - U01G007674-01/PHS HHS/United States
GR  - P01 HL108800-01/HL/NHLBI NIH HHS/United States
GR  - HL 114887/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150415
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - Pulmonary edema of mountaineers
SB  - IM
MH  - Alleles
MH  - Altitude Sickness/genetics/*veterinary
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/*genetics
MH  - Cattle
MH  - Cattle Diseases/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Hypertension, Pulmonary/genetics/*veterinary
MH  - Male
MH  - Up-Regulation
PMC - PMC4399003
MID - NIHMS670441
EDAT- 2015/04/16 06:00
MHDA- 2016/04/06 06:00
PMCR- 2015/04/27
CRDT- 2015/04/16 06:00
PHST- 2015/01/20 00:00 [received]
PHST- 2015/03/06 00:00 [accepted]
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2016/04/06 06:00 [medline]
PHST- 2015/04/27 00:00 [pmc-release]
AID - ncomms7863 [pii]
AID - 10.1038/ncomms7863 [doi]
PST - epublish
SO  - Nat Commun. 2015 Apr 15;6:6863. doi: 10.1038/ncomms7863.