Bovine Respiratory Disease
Prevention: Opportunities for
Genetic Selection in Dairy Cattle
Alison Van Eenennaam, Ph.D.
Cooperative Extension Specialist
Animal Biotechnology and Genomics
Department of Animal Science
University of California, Davis
alvaneenennaam@ucdavis.edu
Twitter: @biobeef
US Bovine Respiratory Disease
Coordinated Agricultural Project
http://www.brdcomplex.org
The “Integrated Program for Reducing Bovine Respiratory Disease Complex
(BRDC) in Beef and Dairy Cattle” Coordinated Agricultural Project is
supported by Agriculture and Food Research Initiative Competitive Grant no.
2011-68004-30367 from the USDA National Institute of Food and Agriculture.
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Bovine Respiratory Disease Consortium
Overview
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What is the BRD CAP?
Advantage of selecting for disease traits
Challenges of selecting for disease traits
Research overview of BRD CAP
Development of a BRD scoring system
Survey of CA dairy calf raising practices
Selection for animals with less
susceptibility to BRD
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“Year in and year out, diseases of the respiratory system are a major
cause of illness and death in cattle from 6 weeks to two years of age.
Sadly, this is as true today as it was 30 years ago despite development
of new and improved vaccines, new broad spectrum antibiotics, and
increased fundamental knowledge as to the cause of disease”
Montgomery, D. 2009. Bovine Respiratory Disease & Diagnostic Veterinary Medicine. Proceedings, The
Range Beef Cow Symposium XXI. December 1, 2 and 3 2009, Casper, WY. Pages 1-6.
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What is Bovine
Respiratory Disease?

Bovine respiratory disease (BRD) is a significant cause of morbidity,
mortality, economic loss, antibiotic use and is an animal welfare concern.

Disease associated with many pathogens, both viral and bacterial

Exacerbated in times of stress


Overall, 18.1% of preweaned dairy heifers experience respiratory disease*
but it is responsible for 22.5% of mortalities in unweaned dairy heifers, and
46.5% in weaned dairy heifers
Economic costs associated with BRD include treatment expense, mortality,
premature culling, reduced growth, impaired fertility and reduced milk
production in adulthood.
* Dairy Heifer Raiser, 2011 An overview of operations that specialize in raising dairy heifers
http://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairyheifer11/HeiferRaiser.pdf
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Bovine Respiratory Disease Consortium
Our goal is to integrate research,
education, and extension activities to
develop cost-effective genomic and
management approaches to reduce the
incidence of BRD in beef and dairy cattle
The objective of BRD CAP project is to reduce the
incidence of bovine respiratory disease by:
• Capitalizing on recent advances in genomics to enable novel
genetic approaches to select for disease-resistant cattle
• Developing genetic tools for selection against BRD susceptibility
• Producing and delivering a variety of educational materials for
beef and dairy cattle producers, and feedlot personnel on best
management practices to reduce disease incidence
• Providing educational opportunities for undergraduate, graduate
and veterinary students to generate a future human resource for
the continued reduction in bovine respiratory disease incidence
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Bovine Respiratory Disease Consortium
http://BRDComplex.org
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Potential benefits of
genomics are greatest for
economically-important
traits that:
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Are difficult or
expensive to measure
Cannot be measured
until late in life or after
the animal is dead
Are not currently
selected for because
they are not routinely
measured
Have low heritability
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Yep, looks like
all of ‘em were
susceptible
Bovine Respiratory Disease Consortium
Need for large
discovery populations

The ready availability of dense single nucleotide
polymorphism arrays (i.e. SNP chips) has given rise to
hitherto unforeseen opportunities to dissect between-host
variation and identify possible genes contributing to this
variation using genome wide association studies(GWAS)

To have the requisite power to meaningfully quantify
genetic variation or perform a genome scan using a dense
SNP chip it is necessary to have datasets comprising
observations on several thousands of individuals.
Bishop, S. C., and J. A. Woolliams. 2010. On the genetic interpretation of disease data. Plos
One 5: e8940.
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Need for careful
“case” definition

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For studies of infectious diseases this usually
necessitates utilizing field data because challenge
experiments of a sufficient scale will not be possible.
However, such field data is very ‘noisy’
– diagnosis of infection or disease may be imprecise; it can be
difficult to determine when infection of an individual occurred
– it is often unclear whether or not apparently healthy individuals
have been exposed to the infection

These factors add environmental noise to the
epidemiological data (i.e. decrease the heritability).
Bishop, S. C., and J. A. Woolliams. 2010. On the genetic interpretation of disease data. Plos
One 5: e8940.
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Bovine Respiratory Disease Consortium
No one said we
are targeting the
low hanging fruit
BRD
Reproduction
Feed Efficiency
Production Traits
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However, BRD
resistance is a very
valuable target

The presence of genetic variation in resistance to
disease, coupled with the increased consumer pressure
against the use of drugs, is making genetic solutions to
animal health problems increasingly attractive.
Newman, S. and Ponzoni, R.W. 1994. Experience with economic weights. Proc. 5th
World Congress on Genetics Applied to Livestock Production. 18:217-223.
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Animal industries have
successfully targeted
selection for disease
resistance
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In dairy cattle, selection programs have been developed
to take advantage of genetic variability in mastitis
resistance, despite the fact that the heritability of clinical
mastitis is low and mastitis resistance has an adverse
correlation with production traits
Chicken breeders have long used breeding to improve
resistance to avian lymphoid leucosis complex and
Marek’s disease
A large major effect locus for swine porcine reproductive
and respiratory syndrome (PRRS) has been identified
Stear, M. J., S. C. Bishop, B. A. Mallard, and H. Raadsma. 2001. The sustainability, feasibility
and desirability of breeding livestock for disease resistance. Res Vet Sci 71: 1-7
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BRD CAP: BRD
field datasets
Case:control field datasets are being developed
for bovine respiratory GWAS
– 3000 animals – case:control design
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2000 dairy calves diagnosed on a collaborating dairy calf rearing
ranch (CA)
1000 dairy (NM) case:control animals will be used to validate loci
associated with BRD in the discovery populations
– All will be genotyped on 800K high density SNP chip
– Pathogens are being characterized using bacteriology and
virology
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Genotype x pathogen interactions
Bovine Respiratory Disease Consortium
Year 1: CA Dairy Calf
Ranch: 70,000 head
capacity
Jessica Davis, DVM
Intern at Veterinary Medicine
Teaching and Research
Center, University of
California, Davis; Tulare
Terry Lehenbaurer, DVM
Sharif Aly, DVM
Pat Blanchard, DVM
California Animal Health and
Food Safety Laboratory System
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Photo credit: Jessica Davis
Bovine Respiratory Disease Consortium
Standardization
of BRD Diagnosis
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1000 case and 1000 control 30-60 day old calves
Use Dr. Sheila McGuirk’s calf respiratory scoring chart
– Temperature, eyes, ears, nose, +/- cough
– Give score and either enroll or not (5 or greater to enroll as case)
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Sample collection
– Blood for DNA
– Nasal swab and deep pharyngeal swab to identify viruses (PCR:
IBR, BVD, BRSV, and Corona) and bacteria (Manheimia
haemolytica, Pasteurella multocida, and Histophilus somni, and
Mycoplasma spp.) present in the nasopharyngeal and pharyngeal
recesses
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http://www.vetmed.wisc.edu/dms/fapm/fapmtools
/8calf/calf_health_scoring_chart.pdf
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Deep
pharyngeal
swab
collection
Blood collection
Nasal swab
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Photo credit: Jessica Davis
Bovine Respiratory Disease Consortium
Sampling location of deep
pharyngeal swab
To culture organisms associated with BRD, pharyngeal
swabs offer a less invasive, less stressful and more rapid
alternative to broncheoalveolor lavage.
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Photo credit: Jessica Davis
Bovine Respiratory Disease Consortium
Control
Calves
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Score control in same way as cases (score of 4 or less)
Try to select animals in the adjacent hutch, same dairy
of origin, and same sex
Collect samples for control animals in same was as case
Try to identify cases and controls in a
relatively constant environment, subjected
to the same exposure and stresses, to
decrease the environmental “noise” of these
field BRD datasets
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CASE AND CONTROL NUMBERS FOR TOP 30 HOLSTEIN A.I. SIRES
Sire
# offspring
# cases
# controls
% cases
% controls
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
36
30
25
19
18
18
16
15
15
14
14
14
13
13
13
13
13
13
13
12
12
12
12
11
11
11
11
11
11
19
12
18
11
12
12
5
7
9
8
10
3
7
8
5
9
9
4
12
7
5
5
9
6
6
5
7
4
3
17
18
7
8
6
6
11
8
6
6
4
11
6
5
8
4
4
9
1
5
7
7
3
5
5
6
4
7
8
53%
40%
72%
58%
67%
67%
31 %
47%
0%
57%
71%
21%
54%
62%
38%
69%
69%
31%
92%
58%
42%
42 %
75%
55%
55%
45%
64%
36%
27%
47%
60%
28%
42%
33%
33%
69%
53%
40%
43%
29%
79%
46%
38%
62%
31%
31%
69%
8%
42%
58%
58%
25%
45%
45%
55%
36%
64%
73%
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P <0.05
**
**
**
Bovine Respiratory Disease Consortium
Preliminary Results:
Dairy study
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In CA over 200,000 calves were screened to obtain
1,003 cases and 1,012 controls over 180 days
Calves identified as BRD cases in the California dairy
study using the criterion of a McGuirk score ≥5 were
significantly associated with positive cultures of BRSV,
Mannheimia haemolytica, Pasteurella multocida,
Histophilus somni, and Mycoplasma spp.
All 2,015 samples tested for BVDV were negative
Neibergs, H.L., C.M. Seabury, J.F. Taylor, Z. Wang, E. Scraggs, R.D. Schnabel, J. Decker, A. Wojtowicz, J.H. Davis, T.W.
Lehenbauer, A.L. Van Eenennaam, S.S. Aly, P.C. Blanchard, B.M. Crossley. (2013). Identification of loci associated with
Bovine Respiratory Disease in Holstein calves. Abstract P0552 Plant & Animal Genome XXI, San Diego, California.
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Preliminary Results:
Dairy study
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A case-control genome wide association study (GWAS) was
conducted on the dairy calf data in the laboratories of H.L. Neibergs
at Washington State University, C.M. Seabury at Texas A&M
University, and J.F. Taylor at the University of Missouri, using four
different analytical approaches.
Heritability estimates for BRDC susceptibility in dairy calves was
21%
The SNP effects explained 20% of the variation in BRD incidence
Neibergs HL, Seabury CM, Wojtowicz AJ, Wang Z, Scraggs E, Kiser J, Neupane M, Womack JE, Van Eenennaam A, Hagevoort GR,
Lehenbauer TW, Aly S, Davis J, Taylor JF. Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned Holstein
calves. BMC Genomics. 2014 Dec 22;15(1):1164.
Neibergs, H.L., C.M. Seabury, J.F. Taylor, Z. Wang, E. Scraggs, R.D. Schnabel, J. Decker, A. Wojtowicz, J.H. Davis, T.W. Lehenbauer,
A.L. Van Eenennaam, S.S. Aly, P.C. Blanchard, B.M. Crossley. (2013). Identification of loci associated with Bovine Respiratory Disease
in Holstein calves. Abstract P0552 Plant & Animal Genome XXI, San Diego, California.
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Future Plans: Dairy
study
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Studies are currently underway to identify the causal mutations
associated with enhanced BRDC susceptibility, as an alternative to
relying on array-based SNP markers as imperfect predictors of these
mutations. (C. M. Seabury, TX)
Additionally, efforts are underway to develop genomic estimates to
enable the development of breeding values (PTA) for resistance to
BRD for ultimate incorporation into national dairy cattle genetic
evaluations (C. P. Van Tassell, MD)
Ultimately, the trait of BRD susceptibility will need to included in the
dairy industry economic selection index ($NetMerit).
The appropriate selection emphasis for this trait will need to be
weighted by its effect on profitability relative to other economicallyimportant traits.
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History of the main changes in USDA
genetic-economic indexes for dairy cattle
and the percentage of relative emphasis on
traits included in the indexes.
Traits
included
USDA genetic-economic index (and year introduced)
PD$
(1971)
MFP$
(1976)
CY$
(1984)
NM$
(1994)
NM$
(2000)
NM$
(2003)
NM$
(2006)
NM$
(2010)
NM$
(2014)
Milk
52
27
−2
6
5
0
0
0
−1
Fat
48
46
45
25
21
22
23
19
22
27
53
43
36
33
23
16
20
PL
20
14
11
17
22
19
SCS
−6
−9
−9
−9
−10
−7
Udder composite
7
7
6
7
8
Feet/legs
composite
4
4
3
4
3
Body size
composite
−4
−3
−4
−6
−5
7
9
11
7
Protein
DPR
CCR
2
HCR
1
CA$
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6
5
5
Bovine Respiratory Disease Consortium
Moving on from the BRD CAP now….
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Genomic selection for
producer-recorded health
event data in US dairy cattle
Computer records for disease conditions used to develop
genomic selection approaches for common health events:
•
•
•
•
•
•
•
cystic ovaries (CYST),
displaced abomasum (DSAB),
ketosis (KETO),
lameness (LAME),
mastitis (MAST),
metritis (METR)
retained placenta (RETP).
134,226 total first-parity records ,174,069 total records
from parities 2 through 5 for 100,635 cows
Parker Gaddis KL, et al. 2014. Genomic selection for producer-recorded health event
data in US dairy cattle. J Dairy Sci. 2014 May;97(5):3190-9.
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Increase in reliability from
genomic information ~ 0.12
Parker Gaddis KL, et al. 2014. Genomic selection for producer-recorded health
event data in US dairy cattle. J Dairy Sci. 2014 May;97(5):3190-9.
Van Eenennaam
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Bovine Respiratory Disease Consortium
http://www.vmtrc.ucdavis.edu/laboratories/epilab/scoringsystem.pdf.
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Bovine Respiratory Disease Consortium
Survey of Calf Rearing Practices
in California
• Betsy Karle, Dairy Farm Advisor, Northern Sacramento Valley
• Alison Van Eenennaam, UC Davis Department of Animal Science
• Phil Kass Thomas Farver, UCD School of Veterinary Medicine
• Lindsay Hulbert, Kansas State University
• Randy Anderson, CDFA - Animal Health Branch
• William Love, Terry Lehenbauer, Sharif Aly, UCD Veterinary Medicine
Teaching & Research Center and UCD School of Veterinary Medicine
Funded by University of California- Division of Agriculture and Natural Resources
Calf Rearing Practices Survey
• Reach out to all California Grade A dairies.
• Identify important & unique management
practices.
• Snapshot of management and producer
reported prevalence.
• Identify cooperators for follow-up,
in-person assessment.
Methods
•
•
•
•
•
Launched at World Ag Expo in Tulare- Feb 2013
Grade A Dairy contacts from CDFA list
Mail-out survey with online option
Reminder card
Second mail-out to non-respondents, UCCE
Farm Advisor follow-up
• Incentive
• Data stored in Access database
Demographics
Number (% of) Responses by Region
Northern
Avg. herd size: 543
CDFA Avg.: 388
8 (3%) 6 (3%)
40 (18%)
78 (34%)
96 (42%)
North Central
Avg. herd size: 1,349
CDFA Avg.: 946
South Central
Avg. herd size: 1,947
CDFA Avg.: 1,919
Southern
Avg. herd size: 1,292
CDFA Avg.: 1,119
15% response rate (7-18% by region)
Average herd size (respondents)1,420 cows
Average herd size (CDFA 2013)1,164 cows
Demographics (cont’d)
100%
100%
90%
80%
71%
Northern
North Valley
South Valley
Southern
Percent of Responses
70%
60%
50%
56%
48%
47%
40%
30%
20%
10%
3%
3%
0%
Raise pre-weaned calves
Organic
0%
Van Eenennaam, A.L. and Young, A.E. 2014. Invited review: Prevalence and impacts of genetically engineered
feedstuffs on livestock populations. Journal of Animal Science 92:4255-4278.
Colostrum Management
What is the source of colostrum for heifer calves?
70%
Percent of Responses
60%
Northern
North Valley
South Valley
Southern
50%
40%
30%
20%
10%
0%
Individual DamNursed from Dam
Pooled
Replacer
None
Calving & Newborn Management
Are maternity/calving pens
group or individual?
How much time do newborn calves typically
spend with their dam?
80%
22%
70%
Group
Individual
60%
Percent of Responses
78%
50%
40%
30%
20%
10%
0%
< 1 hour
Northern
< 1 hour during daytime, > 1
hour at night
North Valley
South Valley
> 1 hour
Southern
Colostrum Management (cont’d)
Is colostrum pasteurized?
<1%
13%
Is colostrum quality tested (i.e.
refractometer or colostrometer)?
86%
33%
58%
Yes
No
7%
Sometimes
1%
All colostrum is tested
Only colostrum from heifers
Sometimes
No
Pre-weaning Management
What is the source of milk fed to calves?
90%
80%
70%
Percent of responses
60%
Northern
50%
North Valley
South Valley
40%
Southern
30%
20%
10%
0%
Milk Replacer
Salable Milk
Waste Milk
Pre-weaning Management (cont’d)
What is the volume of milk or milk
replacer offered at each feeding?
30%
15%
8%
Are any of the following used to treat
or supplement the milk or milk
replacer?
47%
Less than 2 quarts (<4 pints)
2 to 2.5 quarts (4-5 pints)
2.6 to 3 quarts (5.2-6 pints)
More than 3 quarts (>6 pints)
22%
22%
3%
29%
24%
Medicated
Pasteurization
Milk plus Replacer
Other
None
Pre-weaning Management (cont’d)
Approximately what percentage of pre-weaned calves are
typically being treated for pneumonia at any given time?
100%
Northern
North Valley
South Valley
Southern
90%
80%
Percent of responses
70%
60%
50%
40%
30%
20%
10%
0%
<5%
6-25%
Percent of calves being treated for BRD
26-50%
Weaned Calf Management
What is the average age at weaning?
80%
Northern
North Valley
70%
South Valley
Southern
Percent of Responses
60%
50%
40%
30%
20%
10%
0%
< 35 days
35-50 days
51-65 days
> 65 days
Disease Monitoring & Prevention
Is a scoring system or facility specific
protocol used to diagnose pneumonia?
5%
21%
74%
Which of the following signs are regularly used
to diagnose pneumonia in calves on your dairy?
Lung Sounds
Cough
Yes
No
Not Sure
Depressed
Ear Droop
Eye Discharge
Fever
Head Tilt
Nasal Discharge
Rapid Resp Rate
Other
0%
10%
20%
30%
40%
50%
60%
70%
80%
Percent of Respondents
90%
100%
Next Steps
• 100 farm in-person facility evaluation along with assessment of
BRD using validated scoring system to help identify BRD risk factors
• Longitudinal study of 10,000 preweaned calves
• Collect incidence, prevalence, treatment and morbidity data from
birth to weaning
• Develop BRD risk assessment tool
• Also collecting DNA from all of the calves to tie it back to the
genomics project
Risk Assessment, Welfare Analysis, and Extension Education for Dairy Calf Respiratory
Disease Management in California
Funded by University of California- Division of Agriculture and Natural Resources
CONCLUSIONS





Large BRD case:control datasets collected on dairy cattle
Heritability estimates are moderate (~0.2)
GWAS analyses look promising
In the long-term, incorporation of BRD as a health trait
into genetic evaluation programs will require a system to
record standardized BRD diagnoses on farm to enable
the development of a large data set of producerrecorded health data.
Selection for animals with less susceptibility to BRD
offers a promising long-term and permanent approach to
decrease the incidence of this leading natural cause of
death among dairy and beef cattle in the United States
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BRD Coordinated
Agricultural Project:
PD: Jim Womack
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Questions?
The “Integrated Program for Reducing
Bovine Respiratory Disease Complex
(BRDC) in Beef and Dairy Cattle”
Coordinated
Agricultural
Project
is
supported by Agriculture and Food
Research Initiative Competitive Grant no.
2011-68004-30367 from the USDA National
Institute of Food and Agriculture.
*Cough*
Bovine Respiratory Disease Consortium