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

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

Categories: Respiratory system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 611783 (trait) , 603349 (gene)

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".
Heaton et al. (2024): "  A retrospective, matched case-control design with 102 clinical BCHF [bovine congestive heart failure] cases and their unaffected pen mates was used in a genome-wide association study. ... Two independent genomic regions were identified as having the most significant association with BCHF: the arrestin domain-containing protein 3 gene ( ARRDC3), and the nuclear factor IA gene ... . ... A missense variant in ARRDC3 (C182Y) represents a potential functional variant since the C182 codon is conserved among all other jawed vertebrate species observed. A two-SNP test with markers in both genes showed 29% of 273 BCHF cases had homozygous risk genotypes in both genes, compared to 2.5% in 198 similar unaffected feedlot cattle."

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. (2024). 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 54:689-708, 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 101:skad288, 2023. Pubmed reference: 37698445. DOI: 10.1093/jas/skad288.
2022 Heaton, M.P., Harhay, G.P., Bassett, A.S., Clark, H.J., Carlson, J.M., Jobman, E.E., Sadd, H.R., Pelster, M.C., Workman, A.M., Kuehn, L.A., Kalbfleisch, T.S., Piscatelli, H., Carrie, M., Krafsur, G.M., Grotelueschen, D.M., Vander Ley, B.L. :
Association of ARRDC3 and NFIA variants with bovine congestive heart failure in feedlot cattle. F1000Res 11:385, 2022. Pubmed reference: 38680232. DOI: 10.12688/f1000research.109488.2.
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. DOI: 10.1152/jappl.1991.70.2.859.
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. DOI: 10.1093/cvr/8.6.745.
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. DOI: 10.1159/000192263.
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
  • Changed by Imke Tammen2 on 30 Apr 2024