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Bovine Respiratory Disease Consortium

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

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Bovine Respiratory Disease Consortium

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  1. 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. Bovine Respiratory Disease Consortium WDMC 3/5/2015

  2. 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

  3. “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.

  4. 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

  5. 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

  6. http://BRDComplex.org

  7. Yep, looks like all of ‘em were susceptible 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 Bovine Respiratory Disease Consortium WDMC 3/5/2015

  8. 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.

  9. Need for careful “case” definition • 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.

  10. No one said we are targeting the low hanging fruit BRD Reproduction Feed Efficiency Production Traits

  11. However, BRD resistance is a very valuable target Newman, S. and Ponzoni, R.W. 1994. Experience with economic weights. Proc. 5thWorld Congress on Genetics Applied to Livestock Production. 18:217-223. • 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.

  12. Animal industries have successfully targeted selection for disease resistance 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’sdisease • A large major effect locus for swine porcine reproductive and respiratory syndrome (PRRS) has been identified

  13. BRD CAP: BRD field datasets 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

  14. 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 Photo credit: Jessica Davis

  15. 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 (Manheimiahaemolytica, Pasteurellamultocida, and Histophilussomni, and Mycoplasma spp.) present in the nasopharyngeal and pharyngeal recesses

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

  17. Deep pharyngeal swab collection Blood collection Nasal swab Photo credit: Jessica Davis

  18. 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 broncheoalveolorlavage. Photo credit: Jessica Davis

  19. 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

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

  21. 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, Mannheimiahaemolytica, Pasteurellamultocida, Histophilussomni, 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 P0552Plant & Animal Genome XXI, San Diego, California.

  22. Preliminary Results: Dairy study • 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 P0552Plant & Animal Genome XXI, San Diego, California.

  23. Future Plans: 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.

  24. 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.

  25. Moving on from the BRD CAP now….

  26. 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.

  27. 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 AVC 8/1/2014

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

  29. 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

  30. 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.

  31. 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

  32. Demographics Northern Avg. herd size: 543 CDFA Avg.: 388 South Central Avg. herd size: 1,947 CDFA Avg.: 1,919 North Central Avg. herd size: 1,349 CDFA Avg.: 946 15% response rate (7-18% by region) Average herd size (respondents)- 1,420 cows Average herd size (CDFA 2013)- 1,164 cows Southern Avg. herd size: 1,292 CDFA Avg.: 1,119

  33. Demographics (cont’d)

  34. 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.

  35. Colostrum Management

  36. Calving & Newborn Management

  37. Colostrum Management (cont’d)

  38. Pre-weaning Management

  39. Pre-weaning Management (cont’d)

  40. Pre-weaning Management (cont’d)

  41. Weaned Calf Management

  42. Disease Monitoring & Prevention

  43. 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

  44. 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

  45. BRD Coordinated Agricultural Project: PD: Jim Womack

  46. 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

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