OMIA:000841-9913 : Pulmonary hypertension in Bos taurus (taurine cattle)

In other species: chicken , pig , indicine cattle (zebu) , goat , sheep

Categories: Respiratory system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 611783 (trait) , 603349 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Cross-species summary: Hypoxia

Species-specific name: High-altitude pulmonary hypertension (HAPH); bovine congestive heart failure (BCHF); abnormal pulmonary arterial pressure (PAP)

Markers: Newman et al. (2015) reported a "newly identified double variant in the hypoxia inducible factor (HIF2α) gene, Endothelial PAS domain-containing protein 1 (EPAS1), that is highly associated with HAPH and probably represents a gain of function mutation that is prevalent in low-altitude Angus herds and only expresses disease in the hypoxic state at high altitude". This variant comprised two missense mutations, namely A606T and G610S.

From a specially-assembled whole-genome-sequence panel of 96 minimally-related beef sires representing 19 breeds, Heaton et al. (2016) reported four additional missense mutations: E270Q, P362L, A671G, and L701F. Although having no data to test for association, these authors did construct a "rooted phylogenetic tree of eight polypeptide sequences [that] provided a framework for evaluating the likely order of mutations and potential impact of EPAS1 alleles on the adaptive response to chronic hypoxia in U.S. cattle".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
EPAS1 endothelial PAS domain protein 1 Bos taurus 11 NC_037338.1 (28735330..28825665) EPAS1 Homologene, Ensembl , NCBI gene

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000841-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Buchanan, J.W., Flagel, L.E., MacNeil, M.D., Nilles, A.R., Hoff, J.L., Pickrell, J.K., Raymond, R.C. :
Variance component estimates, phenotypic characterization, and genetic evaluation of bovine congestive heart failure in commercial feeder cattle. Front Genet 14:1148301, 2023. Pubmed reference: 37359370. DOI: 10.3389/fgene.2023.1148301.
Kambal, S., Tijjani, A., Ibrahim, S.A.E., Ahmed, M.A., Mwacharo, J.M., Hanotte, O. :
Candidate signatures of positive selection for environmental adaptation in indigenous African cattle: A review. Anim Genet , 2023. Pubmed reference: 37697736. DOI: 10.1111/age.13353.
Pauling, R.C., Speidel, S.E., Thomas, M.G., Holt, T.N., Enns, R.M. :
Genetic parameters for pulmonary arterial pressure, yearling performance, and carcass ultrasound traits in Angus cattle. J Anim Sci , 2023. Pubmed reference: 37698445. DOI: 10.1093/jas/skad288.
2016 Crawford, N.F., Thomas, M.G., Holt, T.N., Speidel, S.E., Enns, R.M. :
Heritabilities and genetic correlations of pulmonary arterial pressure and performance traits in Angus cattle at high altitude. J Anim Sci 94:4483-4490, 2016. Pubmed reference: 27898959. DOI: 10.2527/jas.2016-0703.
Heaton, M.P., Smith, T.P., Carnahan, J.K., Basnayake, V., Qiu, J., Simpson, B., Kalbfleisch, T.S. :
Using diverse U.S. beef cattle genomes to identify missense mutations in EPAS1, a gene associated with pulmonary hypertension. F1000Res 5:2003, 2016. Pubmed reference: 27746904. DOI: 10.12688/f1000research.9254.2.
2015 Neary, J.M., Garry, F.B., Holt, T.N., Brown, R.D., Stenmark, K.R., Enns, R.M., Thomas, M.G. :
The altitude at which a calf is born and raised influences the rate at which mean pulmonary arterial pressure increases with age. J Anim Sci 93:4714-20, 2015. Pubmed reference: 26523564. DOI: 10.2527/jas.2015-9217.
Newman, J.H., Holt, T.N., Cogan, J.D., Womack, B., Phillips, J.A., Li, C., Kendall, Z., Stenmark, K.R., Thomas, M.G., Brown, R.D., Riddle, S.R., West, J.D., Hamid, R. :
Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension. Nat Commun 6:6863, 2015. Pubmed reference: 25873470. DOI: 10.1038/ncomms7863.
2013 Neary, J.M., Gould, D.H., Garry, F.B., Knight, A.P., Dargatz, D.A., Holt, T.N. :
An investigation into beef calf mortality on five high-altitude ranches that selected sires with low pulmonary arterial pressures for over 20 years. J Vet Diagn Invest 25:210-8, 2013. Pubmed reference: 23512918. DOI: 10.1177/1040638713478608.
2011 Newman, J.H., Holt, T.N., Hedges, L.K., Womack, B., Memon, S.S., Willers, E.D., Wheeler, L., Phillips, J.A., Hamid, R. :
High-altitude pulmonary hypertension in cattle (brisket disease): Candidate genes and gene expression profiling of peripheral blood mononuclear cells. Pulm Circ 1:462-9, 2011. Pubmed reference: 22530101. DOI: 10.4103/2045-8932.93545.
2008 Han, H., Hansen, T.R., Berg, B., Hess, B.W., Ford, S.P. :
Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation. Am J Physiol Heart Circ Physiol 295:H382-9, 2008. Pubmed reference: 18502902. DOI: 10.1152/ajpheart.01272.2007.
2007 Holt, T.N., Callan, R.J. :
Pulmonary arterial pressure testing for high mountain disease in cattle. Vet Clin North Am Food Anim Pract 23:575-96, vii, 2007. Pubmed reference: 17920462. DOI: 10.1016/j.cvfa.2007.08.001.
2005 Rhodes, J. :
Comparative physiology of hypoxic pulmonary hypertension: historical clues from brisket disease. J Appl Physiol (1985) 98:1092-100, 2005. Pubmed reference: 15703167. DOI: 10.1152/japplphysiol.01017.2004.
1991 Pringle, J.K., Bright, J.M., Duncan, R.B., Kerr, L., Linnabary, R.D., Tarrier, M.P. :
Pulmonary hypertension in a group of dairy calves. J Am Vet Med Assoc 198:857-61, 1991. Pubmed reference: 2026538.
Zuckerman, B.D., Orton, E.C., Stenmark, K.R., Trapp, J.A., Murphy, J.R., Coffeen, P.R., Reeves, J.T. :
Alteration of the pulsatile load in the high-altitude calf model of pulmonary hypertension. J Appl Physiol (1985) 70:859-68, 1991. Pubmed reference: 2022578.
1987 Stenmark, K.R., Fasules, J., Hyde, D.M., Voelkel, N.F., Henson, J., Tucker, A., Wilson, H., Reeves, J.T. :
Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m. J Appl Physiol 62:821-30, 1987. Pubmed reference: 3558241.
1977 Bisgard, G.E. :
Pulmonary hypertension in cattle. Adv Vet Sci Comp Med 21:151-72, 1977. Pubmed reference: 602866.
1975 Will, D.H., Hicks, J.L., Card, C.S., Alexander, A.F. :
Inherited susceptibility of cattle to high-altitude pulmonary hypertension. J Appl Physiol 38:491-4, 1975. Pubmed reference: 238929.
Will, D.H., Hicks, J.L., Card, C.S., Reeves, J.T., Alexander, A.F. :
Correlation of acute with chronic hypoxic pulmonary hypertension in cattle. J Appl Physiol 38:495-8, 1975. Pubmed reference: 238930.
1974 Weir, E.K., Tucker, A., Reeves, J.T., Will, D.H., Grover, R.F. :
The genetic factor influencing pulmonary hypertension in cattle at high altitude. Cardiovasc Res 8:745-9, 1974. Pubmed reference: 4457227.
1972 Anderson, F.L., Sutton, R.B., Tsagaris, T.J., Kuida, H. :
Spontaneous pulmonary hypertension in the bovine. Am J Physiol 222:561-4, 1972. Pubmed reference: 4553937.
1963 Alexander, A.F., Jensen, R. :
Pulmonary vascular pathology of high altitude-induced pulmonary hypertension in cattle Am J Vet Res 24:1112-22, 1963. Pubmed reference: 14081444.
1962 Grover, R.F., Reeves, J.T. :
Experimental induction of pulmonary hypertension in normal steers at high altitude. Med Thorac 19:543-50, 1962. Pubmed reference: 13950864.
Will, D.H., Alexander, A.F., Reeves, J.T., Grover, R.F. :
High altitude-induced pulmonary hypertension in normal cattle. Circ Res 10:172-7, 1962. Pubmed reference: 14007066.
1960 Alexander, A.F., Will, D.H., Grover, R.F., Reeves, J.T. :
Pulmonary hypertention and right ventricular hypertrophy in catle at high altitude. Am J Vet Res 21:199-204, 1960. Pubmed reference: 13792577.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 02 Nov 2011
  • Changed by Frank Nicholas on 25 Oct 2016
  • Changed by Imke Tammen2 on 28 Jun 2023