title: Myosin heavy chain 15 is associated with bovine pulmonary arterial pressure.
abstract: Bovine pulmonary hypertension, brisket disease, causes significant morbidity and mortality at elevations above 2,000 m. Mean pulmonary arterial pressure (mPAP) is moderately heritable, with inheritance estimated to lie within a few major genes. Invasive mPAP measurement is currently the only tool available to identify cattle at risk of hypoxia-induced pulmonary hypertension. A genetic test could allow selection of cattle suitable for high altitude without the need for invasive testing. In this study we evaluated three candidate genes (myosin heavy chain 15 [MYH15], NADH dehydrogenase flavoprotein 2, and FK binding protein 1A) for association with mPAP in 166 yearling Angus bulls grazing at 2,182 m. The T allele (rs29016420) of MYH15 was linked to lower mPAP in a dominant manner (CC 47.2 ± 1.6 mmHg [mean ± standard error of the mean]; CT/TT 42.8 ± 0.7 mmHg; P = 0.02). The proportions of cattle with MYH15 CC, CT, and TT genotypes were 55%, 41%, and 4%, respectively. Given the high frequency of the deleterious allele, it is likely that the relative contribution of MYH15 polymorphisms to pulmonary hypertension is small, supporting previous predictions that the disease is polygenic. We evaluated allelic frequency of MYH15 in the Himalayan yak (Bos grunniens), a closely related species adapted to high altitude, and found 100% prevalence of T allele homozygosity. In summary, we identified a polymorphism in MYH15 significantly associated with mPAP. This finding may aid selection of cattle suitable for high altitude and contribute to understanding human hypoxia-induced pulmonary hypertension.
authors.affiliation: Medical Research Council, National Institute for Medical Research, Mill Hill, London, United Kingdom ; These two authors contributed equally to the work.
authors.forename: Marianne T
authors.initials: MT
authors.lastname: Neary
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA ; These two authors contributed equally to the work.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Neary
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Gretchen K
authors.initials: GK
authors.lastname: Lund
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Holt
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Franklyn B
authors.initials: FB
authors.lastname: Garry
authors.affiliation: Medical Research Council, National Institute for Medical Research, Mill Hill, London, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mohun
authors.affiliation: Medical Research Council, National Institute for Medical Research, Mill Hill, London, United Kingdom ; Division of Medicine, University College London, London, United Kingdom.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Breckenridge
keywords: MYH15; cattle; genetic polymorphism; high altitude; hypoxia; myosin heavy chain; pulmonary hypertension