Performing Department
Molecular Biology
Non Technical Summary
Pulmonary arterial pressure (PAP) measurements have been used for more than 20 years as a metric for selective breeding against high altitude sickness in cattle. Regardless, calf mortality in high altitude pastures due to Brisket disease is an ongoing problem. Even after many generations (>20 years) of sire selection based on low PAP scores, calf losses due to Brisket disease may exceed 10% in some high altitude herds. As a result, we are proposing to test a conceptually different approach to the problem: the introgression of one, or several mechanisms of resistance to altitude from yak into cattle. Yaks are widely known to exhibit almost complete resistance to the ill effects of altitude and often live at altitudes greater than 14,000 ft. Yaks are cross-fertile with cattle and share a similar karyotype and closely related genome sequences. Yak adaptations to altitude include enlarged lungs and heart and lack of the pulmonary vasoconstrictive response to hypoxia. The transfer of even a single additional mechanism for altitude resistance would be a boon to cattle producers in the Rocky Mountain West. This study will test the feasibility of this approach to improve cattle for high altitude production.
Animal Health Component
100%
Research Effort Categories
Basic
75%
Applied
25%
Developmental
(N/A)
Goals / Objectives
Major Goal: Explore the possibility of incorporating at least partial altitude resistance from yak into commercial beef breeds.Specific Objectives: Generate a population of as many as 50, F1 hybrids (Dzo) between Bos taurus (dam) and Bos grunniens (sire). We will use artificial insemination (AI) on a super-ovulated donor cow followed by embryo capture and storage. Up to 40 surrogate dams will be impregnated to generate a population of full-sibling Dzo hybrids (F1 generation). If the embryo transfer technology proves inefficient with yak-cow hybrids, we will create our F1 generation using standard AI methods.Carry out PAP testing on the full-sibling Dzo calves at 7200 ft using the dam and age-matched steers as control.Carry out necropsies on the Dzo males and collect tissues for future use in histological and molecular breeding studies. (Dzo males are sterile.)Use standard AI to cross all Dzo heifers to the same Bos taurus bull. The resulting F2 calves (Stol) will be tested for pulmonary function at 7200 ft. If time permits, Stol steers will be fed, slaughtered and evaluated for carcass characteristics.
Project Methods
F1 Generation. A single black angus cow will be super-ovulated, subjected to artificial insemination (AI) using frozen semen from a pure-blooded Bos grunniens bull. Embryos will be captured and stored. These technologies are standard practice on cattle at the University of Wyoming and will be carried out by Dr. Scott Lake (Department of Animal Science). Embryos from multiple superovulation cycles on the same donor will be implanted into at least 50 surrogate dams, housed at the Laramie Research and Extension Center. Cows will be calved at the Laramie R&E Center to yield the F1 generation of Dzo. If the embryo capture technology does not work efficiently with the yak-cow hybrids, we will generate our F1 calves using standard AI using yak semen on 40 cows in the UW herd.Assessment of lung physiology and tissue collection. At 14-months of age, we will carry out PAP tesing on all Dzo hybrids. As control, the donor cow will also be tested along with an age-matched cohort of steers. Dr. McCormick will perform PAP testing. We have already purchased the necessary instrumentation and Dr. McCormick is currently on sabbatical leave at Colorado State University working with Dr. Tim Holt to learn the technique of PAP testing.Dzo males are sterile. (Yak x Cow hybrid males recover fertility in the fourth generation of backcrosses to Bos taurus.) Thus, once pulmonary function measurements are obtained, the males will be euthanized and blood, lung and right ventricular heart tissues will be harvested and stored at -80°C. These tissues will be saved as a resource for molecular breeding.F2 generation. As yearlings (16-18 months), female Dzo (F1) calves will be bred to a single Black Angus bull by standard AI. F2 (Stol) calves will be obtained in the spring and reared to age 14-months. Pulmonary function will be assessed as before. F2 (stol) males will be slaughtered, carcass quality will be assessed and tissue samples will be taken and stored for potential use in a molecular breeding program.Primary data analysis: Several potential outcomes are described below, beginning with the result predicted by Anand et al. (1986). Our data should allow us to distinguish among all of these possibilities. As a rule of thumb, we need at least five animals in each class to use the chi square test for significance. Thus, we are planning for a total F1 population of as many as 40 Dzo calves. Based on comparison between the yak and cow genomes, we know that the genomes are co-linear with a high degree of sequence similarity. We presume in all of these scenarios that the unknown locus/loci under investigation will be homozygous recessive for altitude resistance in the donor cow. We will use PAP score and lung histochemistry (males) as indicators of high altitude resistance or susceptibility.If the yak bull is homozygous for high altitude resistance as specified by a dominant, autosomal (non-sex chromosome-encoded) gene, we expect to see 100% of Dzo calves showing complete resistance to altitude. In a backcross to Bos taurus (Dzo dam x Bos taurus bull), we will expect to see a 1:1 ratio of altitude resistant:susceptible among the Stol calves. The data of Anand et al. (1986) is consistent with such a result.If the yak bull proves heterozygous for high altitude resistance, we would expect a 1:1 ratio of resistant:susceptible Dzo calves. The cross of Dzo dams back to a Bos taurus bull would yield a 1:3 ratio of resistant:susceptible Stol calves. This result would be unexpected.Even less likely, would be the scenario where this trait is dominant and sex-linked (encoded on the x chromosome) in the yak bull. To a first approximation, all female Dzo calves would be altitude resistant and all male Dzo calves would be susceptible. This result, however, could be complicated by factors related to expression of genes on the x chromosome in females including somatic mosaicism, cell autonomous expression, skewed X-inactivation, etc.If multiple genes each contribute significantly to high altitude resistance in Yak, the Dzo calves will show continuous variability in PAP score. This type of result is observed in cattle. For example, we bred a set of high altitude resistant cows to a single, altitude-susceptible bull. Among the half-sibling calves, about one-third died prematurely. Among a randomly selected set of 40 half-sibling steers who survived to 14 months of age, we observed a continuous distribution of PAP scores from about 40 to above 120. If we see such a result in the Dzo (F1) calves, we may conclude that introgression of high altitude resistance from yak into cattle is not practical. However, our decision will be determined by additional factors including the range in PAP scores and by the shape of their distribution and histological examination of lung tissues.