Genetics a viable option to reduce bovine respiratory disease

Bovine respiratory disease (BRD), also known as shipping fever, is one of the most prevalent and economically significant diseases within the beef cattle industry. Treatment rates of cattle in feedlots for respiratory disease is more than all other diseases combined, with recent years realizing a marked increase in the disease.

Many feedlot operators report 67 percent to 82 percent of their cattle suffer from respiratory disease. BRD increases costs associated with prevention, treatment and mortalities as well as additional losses due to decreases in carcass weight, daily gain, yield grade and carcass fat.

There are management strategies to reduce BRD; vaccinations, low-stress handling and treatment have been used traditionally and have been shown to reduce the incidence of the disease. The genetic susceptibility to the disease has recently gained attention in an effort to reduce incidence of BRD in feedlot cattle. There is scientific evidence of breed differences in BRD mortality and morbidity.

More recently, some studies have suggested that BRD prevalence in unweaned calves and feedlot cattle is influenced by the genetic makeup of the animal.

Management strategies have been implemented industry-wide with minimal success at disease reduction. BRD continues to be an issue in the beef and dairy industries, making genetics a viable option for reducing the disease in cattle.

Health traits and BRD
The U.S. consumer views animal health to be synonymous with animal welfare. The mere mention of a sick animal conjures up a negative perception in the non-ag public that often associates all of agriculture with “factory farming.”

The beef industry must continue to combat the negative implications of management practices, and animal health should be at the top of every producer’s list of priorities.

Health traits, as related specifically to “disease” and genetic implications, fall into three general categories. The first group is the diseases that are consequences of a defect in the individual’s genetic composition.

The second class contains those diseases associated with non-transmittable environmental challenges such as high-altitude (brisket) disease. The final class represents those diseases related to some specific disease vector or pathogen, whether bacterial, viral or parasitic in nature.

BRD is part of the pathogen category where development of tools for selection is under way through both public and private research-funding groups, including USDA-NIFA and Zoetis.

There are some challenges with this type of research. Some traits such as growth (e.g., birthweight, weaning weight, etc.) and carcass outcomes (e.g., carcass weight, marbling score, etc.) are simple and easy to measure, while BRD and associated implications are difficult to accurately quantify.

Data collected in the field is problematic due to appropriate diagnosis, assumption of equal exposure to the disease-causing agents and measurement of disease severity. This “environmental noise” in field data may partially mask genetic differences in animals treated for BRD versus non-treated animals, making research difficult.

Yet the potential returns of a possible genetic influence of the disease justify further study. Field studies on BRD are likely underestimating the true importance of genetics in BRD incidence and undervalue the potential for breeding decisions to impact disease resistance. The opportunity to examine new approaches using genomic and molecular data is a logical next step to address the health of beef and dairy cattle.

Animals that can be identified that are less susceptible to disease will contribute to sustainability goals, improving health and productivity. The dairy industry has begun selection programs to identify the genetic variability in mastitis resistance. BRD resistance is a clear goal for selective breeding programs similar to mastitis. The ability for DNA testing is becoming more comprehensive and includes a greater number of traits.

It is probable that DNA testing will provide a selection tool for traits with no other information available or with no selection criteria existing at this moment, traits such as feed efficiency and disease resistance.

Research using simulation and terminal sire selection index suggest there would be considerable value associated with the successful development of a DNA test to enable selection for BRD resistance.

To incentivize the inclusion of BRD resistance in selection decisions, a mechanism analogous to a calf-preconditioning bonus could be used to equitably share some of the value derived from reduced feedlot disease incidence and to compensate breeders and producers for reduced selection emphasis on other economically relevant traits.

An interdisciplinary team of veterinarians with BRD complex experience in both dairy and beef cattle, geneticists (with specialties in animal health, disease, immunology, epigenetics and quantitative genetics), epidemiologists, animal behaviorists, microbiologists, livestock economists, and veterinary and livestock cooperative extension specialists developed a successful five-year USDA grant proposal entitled “Integrated Program for Reducing Bovine Respiratory Disease Complex (BRDC) in Beef and Dairy Cattle.”

The goal of this program is to reduce the incidence of BRD in beef and dairy cattle by capitalizing on recent advances in genomics to enable novel genetic approaches to select for cattle less susceptible to disease.

This effort, known as the BRD CAP (Coordinated Agricultural Project), involves a multi-institutional team led by Dr. James Womack at Texas A&M University and involves research groups from Washington State University, University of Missouri, Colorado State University, New Mexico State University and University of California – Davis.

The BRD CAP research plan includes experiments designed to identify loci associated with BRD resistance in beef and dairy cattle.

A preliminary research project in the central valley of California, with the objective of identify host loci associated with susceptibility to BRD in Holstein calves between day 10 and weaning (day 63), led by Dr. Terry Lehenbauer, DVM, associate professor and director, Veterinary Medicine Teaching and Research Center in Tulare, show a strong and moderated association of 155 single nucleotide polymorphisms (SNPs) and BRD.

If BRD resistance is a quantitative trait influenced by many genes, as is expected for this complex trait, a large dataset of case and control animals will be needed to detect all of the large and small effects loci (specific location on the chromosome) on the genome.

Obtaining markers of disease-resistance loci relies on the association between DNA markers and the causative loci. But a marker associated with a trait in one breed is often found not to be associated in the same way in another breed.

This is due to the relatively sparse spacing of markers; this means that they may be located “far” from the causative gene, and the relationship between the DNA marker and the variant of the gene causing different genotypes, and therefore different phenotypes, may change from one breed to another.

On the positive side, the new-generation technology on high-density SNP arrays will provide adequate coverage of the bovine genome to find the right location on the genome associated with disease susceptibility. It is also expected that these technology will enable the development of tests that could work across multiple breeds.

Constructing a large dataset with multiple breeds for disease phenotypes could, as a group, increase the accuracy of tests for all breeds more than any single breed database due to the large number of records.

Reducing the considerable animal morbidity, mortality and economic losses associated with BRD will require the simultaneous development of DNA tests to enable the selection of resistant animals and the incorporation of this trait into breeding objectives of relevance to U.S. beef production systems.

Another project, funded by Zoetis in cooperation with Colorado State University and JBS Five River’s Cattle Feeding, supports the premise that there are genetic differences among animals that contribute to BRD treatment. The project was conducted over two years, with 1,551 steers fed in year one and 1,319 fed in year two of the study.

Animals exhibiting clinical signs of BRD as determined by commercial feedlot personnel were treated following feedlot protocols and classed as positive for BRD. Sires of calves were identified with DNA markers, and that parentage information was subsequently used to estimate heritability.

BRD treatment rates were 45 percent and 7.1 percent in year one and two, respectively, illustrating the difficulties associated with collection of field data given variable rates in incidence across contemporary groups.

Even with the contemporary group differences present in the study, the probability that animals were treated for BRD was 17 percent heritable based on BRD treatment records in that population and the probability that an individual was treated for any health-related problem was 24 percent heritable.

“Any” treatment would include treatments for foot rot, pinkeye, bloat, etc. To put these values in perspective, the heritability of heifer pregnancy is often in this range, as is the heritability of milk production in a number of beef cattle breeds. While not high, both would indicate that there is genetic variability associated with pathogen-associated disease traits, in this particular case, BRD.

Health traits may be complex and complicated in their genetics, but due to the economic relevance, animal well-being and genetic variability among individuals, these traits have potential to decrease the costs for morbidity and mortality on the beef and dairy industry, and therefore increase production.

The leading cause of illness and death in feedlot cattle in the U.S. is BRD. Because some animals are more resistant than others, integrated health traits related to BRD susceptibility or resistance in breeding programs is a positive control approach, but it is important to consider all other economically relevant traits on the genetic evaluation.

Due to new technologies in genomics and molecular biology, new tools to develop DNA tests for BRD will be possible for multiple breeds. This emerging technology has the potential to identify breeding animals with genetic resistance, which would significantly decrease treatment and subsequent production.