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Theses and Dissertations

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Browsing Theses and Dissertations by Subject "altitude"

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    Calcium signaling genes in association with altitude-induced pulmonary hypertension in Angus cattle
    (Colorado State University. Libraries, 2019) Crawford, Natalie Faye, author; Thomas, Milton G., advisor; Coleman, Stephen J., advisor; Enns, R. Mark, committee member; Speidel, Scott E., committee member; Garry, Franklyn B., committee member
    This research used multi-omics technology (i.e., RNA-seq, qPCR for gene expression, SNP discovery and validation) to understand the influence of a particular subset genes on altitude-induced pulmonary hypertension susceptibility in Angus cattle. Three research aims were established to test the hypothesis that calcium-related genes may be associated with pulmonary hypertension in beef cattle. Data and samples utilized for the research came from the Colorado State University Beef Improvement Center Angus herd managed at 2,150 m of altitude. Transcriptome data from 6 tissues and 14 hypertensive and normotensive Angus steers were utilized for differential expression and pathway analyses. The objectives of the first aim were to: 1) to estimate and identify differentially expressed genes from RNA-Seq and pathway analyses, and 2) select putative candidate genes to analyze with qPCR (gene expression level). The largest number of DE genes was revealed in aorta (n = 631) and right ventricle (n = 2,183) samples. Top canonical pathways related to calcium signaling or utilization included: synaptic long-term depression, signaling by Rho family GTPases, and oxidative phosphorylation. Genes regulating calcium availability and utilization were expressed differently (log2 fold change > 0.589, < -0.589; P < 0.05) in Angus cattle with and without pulmonary hypertension. Isolated RNA from cardiac muscle (n = 9) and control muscle (n = 2) tissues from hypertensive and normotensive Angus steers were utilized to estimate gene expression using quantitative reverse transcription PCR in the candidate genes from Chapter 3. The objectives of this chapter were: 1) to establish the most appropriate reference genes in cardiac muscle tissues, and 2) to estimate and validated relative gene expression of calcium-related genes in cardiac muscle tissues using qPCR methods. Differences (P < 0.0055) among hypertensive and normotensive steers were estimated for right papillary muscle and right cardiac ventricle tissues (top, middle, and bottom) in candidate genes: ASIC2, EDN1, NOX4, PLA2G4A, RCAN1, and THBS4. Results of the current study validate the expression differences previously established of genes that regulate the availability and utilization of calcium with PH status in Angus steers at high altitude. Variant detection and association analyses were completed with 2 sets of available -omics data to identify opportunities for development of selection tools for reduced susceptibility to PH. The objectives of the third aim were to: 1) detect single nucleotide polymorphisms (SNP) in the transcriptome of 6 tissues, and 2) identify functional consequences of those variants associated with validated candidate genes from qPCR analyses. Pooled Angus sample analysis revealed 68 SNP in the 6 candidate genes: ASIC2, EDN1, NOX4, PLA2G4A, RCAN1, and THBS4. Thirty-eight SNP were revealed in the hypertensive group and 8 SNP in the normotensive steer group. Ten of the 68 identified SNP are utilized on large density commercially available bovine SNP chips (Illumina BovineHD BeadChip; GeneSeek Genomic Profiler HD; GeneSeek Genomic Profiler HDv2; Affymetrix Axiom Bovine). Analysis of transcriptome data identified SNP within genes regulating calcium availability and utilization, enhancing our understanding of sequence polymorphisms that may be involved in regulating pulmonary hypertension in Angus cattle raised at high altitude. These SNP are available for additional validation and potential use in genetic improvement programs.
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    Pulmonary arterial pressure: repeated measures and dynamics due to changes in altitude and age
    (Colorado State University. Libraries, 2022) Zimprich, Taylor R., author; Thomas, Milt, advisor; Speidel, Scott, committee member; Holt, Tim, committee member
    High Altitude Disease (HAD) in cattle is a consequence of pulmonary hypertension (PH) induced by hypoxia at elevations > 1,500 m. Pulmonary arterial pressure (PAP) is a phenotypic indicator of animal susceptibility to PH and HAD and is moderately heritable (h2 = 0.26 to 0.34). The goal of this thesis was to evaluate repeated measures of PAP and dynamics. This goal was achieved with two studies and three objectives: 1) to explore and estimate correlations between different ages and elevations, 2) to determine usefulness of yearling moderate altitude PAP in beef bulls that are transported to high elevation for short- and longer-term management, and 3) to determine usefulness of feedlot entry PAP to additional PAP measures as the cattle approach finishing and harvest. The objective of Study I (Chapter 3) was to determine significant variables and estimate correlation between PAP measurements at moderate altitude and high altitude at differing ages. This scenario often occurs in the Western U.S. beef industry. Data consisted of breed, sire, mean PAP (mPAP) measures at each collection date, elevation, and bull age, from 2017-2019 (n = 89) spring-born bulls at the Colorado State University (CSU) Agriculture Research, Development, and Education Center (ARDEC; 1,524 m). A potential 5 PAP measurements were collected from each bull: 1) Weaning PAP at ARDEC (1,525 m); 2) Yearling PAP at ARDEC; 3) PAP after acclimating for 28 days at Fort Lewis College (FLC; 2,470 m), Hesperus, CO; 4) before returning to ARDEC from FLC after 110 days at FLC; and 5) after re-acclimating for 57 days to the moderate elevation at ARDEC when the bulls were 557 ± 2.92 d (18 mo) of age. In model development, yearling PAP measurement, elevation, and age were determined to be important (P < 0.05) sources of variation. Also, PAP increased (P < 0.05) from moderate altitude to high altitude. In Study II (Chapter 4), yearling PAP in the model accounted for more variation in the prediction of the initial high-altitude PAP than it did in the prediction of the subsequent high altitude PAP measurements. Results of this study suggested that the yearling PAP measurement collected at 1,525 m was only a moderate predictor of a PAP measurement collected after 21 days at 2,470 m and these types of predictions weaken after ~ 90 days at high elevation. Overall, Study II (Chapter 4) suggested that as time increased (p < 0.05) between the mPAP measures the amount of variation accounted by the initial mPAP measure declined (p < 0.05). However, PAP has been considered to be the most accurate indicator of an individual's susceptibility to HAD if is measured at high altitude and near 18 months of age (Holt and Callen, 2007). This thesis suggested that yearling PAP measured at moderate elevations was a moderate and short-term indicator of future PAP performance in beef bulls when moving to high altitudes. Yearling PAP measurements are likely less indicative of PAP, the longer bulls reside at high elevation. It should be noted that high-altitude PAP observations will likely have higher correlations and be a stronger indicator to future high-altitude PAP measures. The altitude of the ARDEC facility (1,525 m) of CSU is moderate; therefore, questionable if it yields enough hypoxic stress to determine if a bull has PAP that will be acceptable or unacceptable for lifetime residence in a mountainous beef production system. Breed was not a significant variable in this thesis. This is likely due to limited numbers being evaluated in each breed. To further study breed influence, greater numbers of bulls being analyzed is necessitated. Therefore, this challenge warrants additional research when considering the diversity of beef operations in the Western US.