Battling BRD with genomics

Battling BRD with genomics

The genes associated with the disease complex are moderately heritable.

If there’s an animal health problem that needs solving, it’s shipping fever, or BRDC. That’s because bovine respiratory disease complex (BRDC) continues to be the leading cause of cattle sickness and death in feedlots and stocker cattle operations, costing the industry more than $1 billion annually.

Worse, both data and daily experience suggest managing and treating cattle with BRDC is more difficult than ever, despite more advanced vaccines and antibiotics. That’s why plenty of folks had their fingers crossed when researchers began the Bovine Respiratory Disease Coordinated Agricultural Project (BRD CAP) several years ago.

In simple terms, researchers are exploring whether genes affecting BRDC susceptibility can be identified, and if so, whether those genes occur with enough frequency and heritability to offer selection potential. Researchers are in the last year of the five-year project, but are seeking a one-year extension.

BRD
Diagnosing BRDC is an inexact science. For every head exhibiting clinical symptoms, others affected by BRDC are able to hide their symptoms and go unnoticed — and untreated.

“What’s exciting is that some people didn’t think we’d find much difference,” says Holly Neibergs, a beef cattle geneticist at Washington State University and a member of the BRD CAP team. “But, there are some genes that have large enough effects that we believe we can select for the variants that reduce BRDC susceptibility and make a difference.”

The difference would be huge. Working with the feedlot data collected as part of the project, BRD CAP economists used the most current national estimate of 16.2% BRDC prevalence in feedlots.

They calculate that 4,071,854 feedlot cattle were likely afflicted with BRDC in 2013. Based on a single treatment cost and lost carcass value, they say a conservative estimate is $253.97 lost per head. That’s an estimated total of $1.034 billion lost by the feedlot industry.

BRD CAP in a nutshell

The BRD CAP is a unique, collaborative project — funded by the USDA National Institute of Food and Agriculture — comprised of six land-grant universities, the Agricultural Research Service and an interdisciplinary team of 27 researchers that includes veterinarians, geneticists, microbiologists, epidemiologists, animal behaviorists and livestock economists. All have experience with BRDC from the vantage point of their specialties, which include immunology, epigenetics and quantitative genetics. You can find more of the specifics at brdcomplex.org, which is a site dedicated to the project.

The project looks at BRDC susceptibility, separately, in both beef cattle and dairy cattle. For beef, DNA was collected from 1,000 head of Bos taurus, crossbred feedlot cattle in Washington, and another 1,000 head from a feedlot in Colorado. Researchers screened hundreds of thousands of head via cooperative dairies and feedlots in order to identify candidates that were more or less susceptible to BRDC.

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At the beginning of the year, researchers were completing the first analysis of feedlot data. “The heritability of BRD susceptibility in the 2,000 beef feedlot animals is similar to, or a little better than, what we found in the Holstein calves,” Neibergs says. For dairy, BRDC susceptibility is estimated to be moderately heritable at 0.21.

That’s a higher level of heritability than achieved in previous field studies. Researchers believe one reason is their use of an objective scoring system to more precisely diagnose BRDC.

So, identifying genomic regions associated with BRDC susceptibility offers the potential to create commercial assays that could be used to determine susceptibility levels of individual cattle. Ultimately, it also means breed associations, AI companies and the like could incorporate the identified genes into breeding values and genetic evaluation, so that producers could select cattle less likely to produce calves susceptible to BRDC.

Both of those possibilities are likely at least a couple of years down the road.

Long and winding road

To understand why, it will pay to hobble your pony, as this part of the explanation tends to run fast and deep for many of us.

Forgetting the genomics discussion for a moment, diagnosing BRDC is inexact at best. For every head exhibiting a telling clinical symptom like a snotty nose, runny eyes, droopy ears or a cough, countless others affected by BRDC go unnoticed — and untreated. Lung lesions from infected and presumably healthy calves underscore that fact in a variety of studies.

In the BRD CAP, 67.7% of the cattle diagnosed with BRDC had lung lesions; 67.2% of the healthy control population did.

That’s where the aforementioned objective method of diagnosing BRDC comes into play. Researchers used nasal and throat swabs — culture tests — for bacteria and PCR detection for viruses. They also used the McGuirk diagnostic system, which assigns scores to cattle based on observations of temperature, nasal discharge, ocular discharge, ear position, head tilt and coughing. This latter system was developed for use with dairy calves, but researchers found it serves beef cattle admirably, too.

Bovine respiratory disease complex (BRDC) continues to be the leading cause of cattle sickness and death in feedlots and stocker cattle operations, costing the industry more than $1 billion annually.

Profiles of the sick cattle were compared with the healthy ones to see if there were any genetic markers associated with reduced susceptibility to BRDC. This process is known as a Genome-Wide Association Study (GWAS).

“The first genome-wide association study was conducted for the Colorado and Washington cattle using two different analytical approaches and by using one of two phenotypes,” Neibergs explains. “We either called an animal sick or healthy for our case-control analysis, or we gave them a health score based on the McGuirk diagnostic system.

“Our QTL results are similar with both phenotypes. We also looked at different ways of diagnosing BRD and how that affects the heritability for BRD susceptibility,” Neibergs says. “From our data, the McGuirk system does a good job in diagnosing BRD with good heritability estimates. However, our results could also be used to identify which clinical signs tend to be associated with higher estimates of heritability for BRD than others.”

QTL is short for quantitative trait locus. This is a segment of DNA that varies in its chemical composition (DNA sequence) and has been found to be associated with a trait. For example, one form of the DNA could be associated with susceptibility to BRDC, whereas another form would be associated with higher resistance to BRDC.

“We know there are several million genetic differences between cattle,” Neibergs explains. However, knowing where some gene markers (genes or DNA sequences) are means researchers can use a process called imputation to predict the DNA sequence which lies in between. So, analysts can fairly accurately predict the entire genome of these animals.

In the case of the BRDC CAP, researchers used a genotyping chip to collect about 778,000 gene markers for each of the 2,000 beef calves.

“Next, we will choose the markers with the largest effects on BRD susceptibility, and then identify feedlot cattle that will be the most informative for these regions and then sequence the whole genomes of these cattle,” Neibergs explains. “Genotypes of all 2,000 of the feedlot cattle will be imputed up to whole genome sequence, and the accuracy of the imputation will be checked by the sequenced animals.”

Then the GWAS will be conducted again to further narrow the region for each QTL, and to identify other QTLs with large effects that may have been missed with the initial analyses. “From these data, a genotyping assay will be developed to validate these QTLs in new beef populations, and to confirm the imputation QTLs. This will probably be completed at the end of this year.”

Once verified, Neibergs explains these QTLs can be added to commercial genotyping platforms for industry use. At this stage, she says it appears there are 10 to 20 large-effect QTLs that are associated with BRDC susceptibility.

Hopes are that the identified BRDC markers will predictive across beef breeds.

“The cattle evaluated so far have been crossbred,” Neibergs explains. “Since purebred cattle have not yet been evaluated, it is not known how large of an effect each of the QTLs will have in different purebred breeds. At some point, purebred cattle will also need to be evaluated so that accurate predictions for them can be developed.” 

Curt Van Tassel at the USDA will also be working on bringing EPDs or breeding values to the beef side when we are at that stage with the beef cattle, Neibergs adds. As it is, there is currently no breed-wide or industry-wide approach to collect BRDC phenotypes, let alone collect them in a standardized fashion.

Members of the BRDC CAP participated in a Beef Improvement Federation committee to provide recommendations to establish guidelines for collecting BRDC information that can be used to understand the impacts of BRDC, and to assist in establishing breeding values for BRD.

In the meantime, Neibergs says, “We are very interested in working with breed associations and other industry partners to obtain additional samples with BRDC phenotypes, to be able to do more extensive verification. This will be important as we determine how important each of these QTLs are in each breed and in different regions of the country.”

Individuals or organizations interested in providing such information should contact Neibergs at [email protected].

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