Using diverse U.S. beef cattle genomes to identify missense mutations in EPAS1, a gene associated with high-altitude pulmonary hypertension.

Michael P. Heaton, Timothy P.L. Smith, Jacky K. Carnahan, Veronica Basnayake, Jiansheng Qiu, Barry Simpson, Theodore S. Kalbfleisch

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The availability of whole genome sequence (WGS) data has made it possible to discover protein variants in silico. However, existing bovine WGS databases do not show data in a form conducive to protein variant analysis, and tend to under represent the breadth of genetic diversity in U.S. beef cattle. Thus, our first aim was to use 96 beef sires, sharing minimal pedigree relationships, to create a searchable and publicly viewable set of mapped genomes relevant for 19 popular breeds of U.S. cattle. Our second aim was to identify protein variants encoded by the bovine endothelial PAS domain-containing protein 1 gene ( EPAS1), a gene associated with high-altitude pulmonary hypertension in Angus cattle. The identity and quality of genomic sequences were verified by comparing WGS genotypes to those derived from other methods. The average read depth, genotype scoring rate, and genotype accuracy exceeded 14, 99%, and 99%, respectively. The 96 genomes were used to discover four amino acid variants encoded by EPAS1 (E270Q, P362L, A671G, and L701F) and confirm two variants previously associated with disease (A606T and G610S). The six EPAS1 missense mutations were verified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays, and their frequencies were estimated in a separate collection of 1154 U.S. cattle representing 46 breeds. A rooted phylogenetic tree of eight polypeptide sequences 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. This public, whole genome resource facilitates in silico identification of protein variants in diverse types of U.S. beef cattle, and provides a means of translating WGS data into a practical biological and evolutionary context for generating and testing hypotheses.

Original languageEnglish
Article number2003
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 Heaton MP et al.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)
  • Pharmacology, Toxicology and Pharmaceutics (all)


Dive into the research topics of 'Using diverse U.S. beef cattle genomes to identify missense mutations in EPAS1, a gene associated with high-altitude pulmonary hypertension.'. Together they form a unique fingerprint.

Cite this