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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Genetics and Animal Breeding » Research » Publications at this Location » Publication #326510
Title: Using diverse U.S. beef cattle genomes to identify missense mutations in EPAS1, a gene associated with high-altitude pulmonary hypertension

Author
item Heaton, Michael - Mike
item Smith, Timothy - Tim
item Carnahan, Jacky
item BASNAYAKE, VERONICA - Geneseek Inc, A Neogen Company
item QIU, JIANSHENG - Geneseek Inc, A Neogen Company
item SIMPSON, BARRY - Geneseek Inc, A Neogen Company
item KALBFLEISCH, THEODORE - University Of Louisville

Submitted to: International Society for Animal Genetics (ISAG)
Publication Type: Abstract Only
Publication Acceptance Date: 4/22/2016
Publication Date: 7/25/2016
Citation: Heaton, M.P., Smith, T.P.L., Carnahan, J.K., Basnayake, V., Qiu, J., Simpson, B., Kalbfleisch, T.S. 2016. Using diverse U.S. beef cattle genomes to identify missense mutations in EPAS1, a gene associated with high-altitude pulmonary hypertension [abstract]. 35th International Society for Animal Genetics (ISAG), July 23-27, 2016, Salt Lake City, UT. Poster #P6026.

Interpretive Summary:

Technical Abstract: The availability of whole genome sequence (WGS) data has made it possible to discover protein variants in silico. However, bovine WGS databases comprised of related influential sires from relatively few breeds tend to under represent the breadth of genetic diversity in U.S. beef cattle. Thus, our first aim was to use beef sires sharing minimal pedigree relationships, to create a searchable, publicly viewable set of 96 mapped genomes from 19 breeds of U.S. cattle. Our second aim was to use these genomes to identify protein variants, like those encoded by the endothelial PAS domain-containing protein 1 gene (EPAS1). This gene encodes the hypoxia inducible transcription factor 2A (HIF2A) and has been associated with high-altitude pulmonary hypertension in American Angus cattle. For each bull sequenced, the identity and quality of its mapped WGS data was evaluated by comparing its single nucleotide polymorphism (SNP) genotypes to those derived from other genotyping methods. In these comparisons, the average read depths, scoring rates, and accuracies exceeded 12, 99%, and 99%, respectively. The power for using these genomes to identify protein variants was demonstrated by analyzing EPAS1. Six amino acid variants were observed among the 96 bulls, including those previously reported at positions 606 and 610 (i.e., E270Q, P362L, A606T, G610S, A671G, and L701F). Codon genotypes were independently confirmed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays. A network of seven distinct HIF2A polypeptide sequences was inferred by maximum parsimony resulting in 28 possible diploid combinations. Knowledge of these HIF2A variants provides a framework for evaluating the impact of EPAS1 alleles on the adaptive response to hypoxia in U.S. cattle. Thus, 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 context for hypothesis testing.