Bovine Respiratory Disease Consortium Bovine Respiratory Disease Prevention: Opportunities for Genetic Selection in Dairy Cattle WDMC 3/5/2015 Alison Van

Bovine Respiratory Disease Consortium

Bovine Respiratory Disease Prevention: Opportunities for Genetic Selection in Dairy Cattle

WDMC 3/5/2015

Alison Van Eenennaam, Ph.D.Cooperative Extension SpecialistAnimal Biotechnology and Genomics Department of Animal Science University of California, [email protected]: @biobeefUS 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.

mailto:[email protected]

http://www.brdcomplex.org/

Bovine Respiratory Disease ConsortiumWDMC 3/5/2015

Overview

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


“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.


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

http://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairyheifer11/HeiferRaiser.pdf




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

http://www.google.com/imgres?imgurl=http://www.watergovernance.net/images/ucdavis_logo.gif&imgrefurl=http://www.watergovernance.net/&usg=__8BprodE7_M_aP5v2SMxJUxNcXME=&h=519&w=541&sz=111&hl=en&start=2&zoom=1&itbs=1&tbnid=SYWkkILaL0lBhM:&tbnh=127&tbnw=132&prev=/images?q=uc+davis+logo&hl=en&gbv=2&tbs=isch:1




http://www.ars.usda.gov/SP2UserFiles/Place/62060000/graphics/arslogo.jpg



http://BRDComplex.org







Potential benefits of genomics are greatest for economically-important traits that:

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

Yep, looks like all of ‘em were susceptible









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.

Need for large discovery populations








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.

Need for careful “case” definition








No one said we are targeting the low hanging fruit

BRD

Feed Efficiency

Production Traits

Reproduction








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. 5 th World Congress on Genetics Applied to Livestock Production. 18:217-223.

However, BRD resistance is a very valuable target








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

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

Animal industries have successfully targeted selection for disease resistance








Case:control field datasets are being developed for bovine respiratory GWAS

– 3000 animals – case:control design 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

Genotype x pathogen interactions

BRD CAP: BRD field datasets








Year 1: CA Dairy Calf Ranch: 70,000 head capacity

Jessica Davis, DVMIntern at Veterinary Medicine Teaching and Research Center, University of California, Davis; Tulare Terry Lehenbaurer, DVMSharif Aly, DVMPat Blanchard, DVMCalifornia Animal Health and Food Safety Laboratory System

Photo credit: Jessica Davis


Standardization of BRD Diagnosis

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)

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








http://www.vetmed.wisc.edu/dms/fapm/fapmtools/8calf/calf_health_scoring_chart.pdf








Nasal swab

Blood collection Deep pharyngeal swabcollection



To culture organisms associated with BRD, pharyngeal swabs offer a less invasive, less stressful and more rapid alternative to broncheoalveolor lavage.

Sampling location of deep pharyngeal swab



Control Calves

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


Sire #

offspring# cases

# controls

% cases % controls P <0.05

1 36 19 17 53% 47% 2 30 12 18 40% 60% 3 25 18 7 72% 28% **4 19 11 8 58% 42% 5 18 12 6 67% 33% 6 18 12 6 67% 33% 7 16 5 11 31 % 69% 8 15 7 8 47% 53% 9 15 9 6 0% 40%

10 14 8 6 57% 43% 11 14 10 4 71% 29% 12 14 3 11 21% 79% **13 13 7 6 54% 46% 14 13 8 5 62% 38% 15 13 5 8 38% 62% 16 13 9 4 69% 31% 17 13 9 4 69% 31% 18 13 4 9 31% 69% 19 13 12 1 92% 8% **20 12 7 5 58% 42% 21 12 5 7 42% 58% 22 12 5 7 42 % 58% 23 12 9 3 75% 25% 24 11 6 5 55% 45% 25 11 6 5 55% 45% 26 11 5 6 45% 55% 27 11 7 4 64% 36% 28 11 4 7 36% 64% 29 11 3 8 27% 73% 30 11 2 9 18% 82% **

CASE AND CONTROL NUMBERS FOR TOP 30 HOLSTEIN A.I. SIRES








Preliminary Results: Dairy study

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.








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.

Preliminary Results: Dairy study








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 economically-important traits.

Future Plans: Dairy study








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

Protein 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

DPR 7 9 11 7

CCR 2

HCR 1

CA$ 6 5 5








Moving on from the BRD CAP now….








Genomic selection for producer-recorded health event data in US dairy cattle

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.

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







Bovine Respiratory Disease ConsortiumWDMC 3/5/2015 Van Eenennaam AVC 8/1/2014

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.







Bovine Respiratory Disease ConsortiumWDMC 3/5/2015 http://www.vmtrc.ucdavis.edu/laboratories/epilab/scoringsystem.pdf.

http://www.vmtrc.ucdavis.edu/laboratories/epilab/scoringsystem.pdf

• 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

Survey of Calf Rearing Practices in California

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

40 (18%)

96 (42%)

78 (34%)

8 (3%) 6 (3%)

Number (% of) Responses by Region

SouthernAvg. herd size: 1,292

CDFA Avg.: 1,119

South CentralAvg. herd size: 1,947

CDFA Avg.: 1,919North Central

Avg. herd size: 1,349CDFA Avg.: 946

NorthernAvg. herd size: 543

CDFA Avg.: 388

15% response rate (7-18% by region)Average herd size (respondents)-

1,420 cowsAverage herd size (CDFA 2013)-

1,164 cows

Demographics (cont’d)

Raise pre-weaned calves Organic0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%100%

47%

56%

3%

48%

3%

71%

0%

NorthernNorth ValleySouth ValleySouthern

Perc

ent o

f Res

pons

es

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

Individual Dam Nursed from Dam

Pooled Replacer None0%

10%

20%

30%

40%

50%

60%

70%What is the source of colostrum for heifer calves?


Perc

ent o

f Res

pons

es

Calving & Newborn Management

78%

22%

Are maternity/calving pens group or individual?

Group Individual

< 1 hour < 1 hour during daytime, > 1 hour at night

> 1 hour0%

10%

20%

30%

40%

50%

60%

70%

80%

How much time do newborn calves typically spend with their dam?

Northern North Valley South Valley Southern

Perc

ent o

f Res

pons

es

Colostrum Management (cont’d)13%

86%

<1%

Is colostrum pasteurized?

Yes NoSometimes

33%

1%

7%

58%

Is colostrum quality tested (i.e. refrac-tometer or colostrometer)?

All colostrum is tested Only colostrum from heifersSometimes No

Pre-weaning Management

Milk Replacer Salable Milk Waste Milk0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

What is the source of milk fed to calves?


Perc

ent o

f res

pons

es

Pre-weaning Management (cont’d)

22%

29%24%

4%

22%

Are any of the following used to treat or supplement the milk or milk re-

placer?

Medicated Pasteurization Milk plus Replacer Other None

8%

47%15%

30%

What is the volume of milk or milk replacer offered at each feeding?

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)

Pre-weaning Management (cont’d)

<5% 6-25% 26-50%0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Approximately what percentage of pre-weaned calves are typically being treated for pneumonia at any given time?


Percent of calves being treated for BRD

Perc

ent o

f res

pons

es

Weaned Calf Management

< 35 days 35-50 days 51-65 days > 65 days0%

10%

20%

30%

40%

50%

60%

70%

80%

What is the average age at weaning?NorthernNorth ValleySouth ValleySouthern

Perc

ent o

f Res

pons

es

Disease Monitoring & PreventionIs a scoring system or facility specific

protocol used to diagnose pneu-monia?

21%

74%

5%

Is a scoring system or facility specific protocol used to diagnose pneu-

monia?

Yes No Not Sure

Lung Sounds

Cough

Depressed

Ear Droop

Eye Discharge

Fever

Head Tilt

Nasal Discharge

Rapid Resp Rate

Other

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Which of the following signs are regularly used to diagnose pneumonia in calves on your dairy?

Percent of Respondents

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 producer-recorded 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








BRD Coordinated Agricultural

Project:PD: Jim Womack







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.

Bovine Respiratory Disease Consortium

Questions?

Documents

Bovine Respiratory Disease Consortium Bovine Respiratory Disease Prevention: Opportunities for Genetic Selection in Dairy Cattle WDMC 3/5/2015 Alison Van