Selecting for Favorable Genetic Response to Disease

1. Selecting for Favorable Genetic Response to Disease Gary Snowder, PhD Research Geneticist USDA, ARS, USMARC

2. Outline • Justification • Challenges • Current research on Genetic Resistance to BRD and IBK

3. Justifications for Genetic Selection

4. Justifications • No new class of antibiotics in over 30 years • Emergence of new diseases(BSE, Avian Flu, CWD) • Increase in disease transmission(Daszak et al., 2000) • Intensive mgmt • Wildlife to livestock transmission (Brucellosis, Avian Flu) • Therapeutic treatment costs are higher

5. Justifications • Microbes are antibiotic resistance • No available vaccine or antibiotic • A variety of pathogens infect the host in a similar manner or pathway. • “Organic” labeled product

6. Justification • Rarely will all animals exhibit clinical symptoms. • Cattle breeds differ for disease related traits • Tick borne diseases (Wambura et al., 1998) • Pinkeye (Snowder et al., 2005a) • Bovine respiratory disease (Snowder et al., 2005b)

7. Justifications • New consumer expectations • Meat free of drug residue • Meat animals live a healthy and happy life

8. Breeding for societally important traits in pigs1 E. Kanis*,2, K. H. De Greef , A. Hiemstra*,3 and J. A. M. van Arendonk† *Animal Breeding and Genetics Group, Wageningen University, 6700 AH Wageningen, The Netherlands; and †Animal Sciences Group, 8200 AB Lelystad, The Netherlands 2 J. Anim. Sci. 2005, 83:948-957 Consumers expect meat animals raised with better welfare, produced in an environmentally friendly manner and, free of feed “additives”, antibiotics, and vaccines.

9. Justification: Disease liability can be traced back to owner Source: www.usaip.info

10. Challenges

11. The immune system is highly complex. Only the nervous system is more complex. More complex than reproduction, growth, lactation, or feed efficiency.

12. Challenges • Selection for animals resistant to a particular pathogen may • make that pathogen more virulent, • make the host more susceptible to another microbe

13. Challenges • Genetic correlations between production traits and disease resistance are often undesirable • Milk yield in dairy cattle has a positive correlation with many disease traits(Simianer et al., 1991; van Dorp et al., 1998) • Selection for growth rate in turkeys increased their susceptibility to Newcastle disease(Sacco et al., 1994) • Growth rate in mice is genetically associated with over 100 physiologic, metabolic, and microbial susceptible diseases (nih.gov) • In beef cattle, these correlations have not been defined.

14. Challenges Microbes can change their genetic make-up faster than livestock.

15. Challenges ● Many factors influence disease resistance.

16. Challenges • Difficult to identify phenotype for disease resistance. • False assumption that all healthy animals are disease resistant.

17. Challenges • Some diseases are caused by a variety of microbes Calf Pneumonia caused by: VirusesInfectious Bovine Rhinotracheitis (IBR), Bovine Viral Diarrhea (BVD), Bovine Respiratory Syncytial (BRS), and Parainfluenza 3 (PI3) Bacteria(Mannheimia haemolytica, Pasteurella multocida, Haemophilus somnus) Mycoplasmas(Ellis, 2001)

18. STRESS + PATHOGENS = DISEASE PATHOGENS + STRESS = DISEASE

19. So with some diseases we might be better to select for resistant to “stress”??

20. Can we select for genetic resistance to a disease?

21. Genetic research of human diseases, especially molecular genetics, is far ahead of livestock research.

22. Highly successful in plants Corn Wheat Oats Bean Broccoli Cabbage Carrots Cucumber Peppers Tomato Melon Squash Genetically Resistance to: Fungi Viruses Nematodes Wilt Blight Leafspot Root rot Sunspot

23. Disease Resistance is Heritable Mastitis .02 Somatic Cell Score .15 Pinkeye .22 Respiratory .11 to .48

24. Current research on the influence of genetics on resistance to BRD and IBK

25. Infectious bovine keratoconjunctivitis (IBK), pinkeye Introduction • Annually affects > 10 million calves in the USA • Estimated economic loss > $150 million (Hansen, 2001). • 29% of cattle operations reported IBK as an economically important disease (NAHMS, 1998)

26. Incidence of IBK across years

27. Mar20 Apr19 May19 June18 July18 Aug17 Sept16 Oct16 Incidence of IBK by Date

28. Most common bacterial pathogen is Moraxella bovis

29. Are there breed differences?

31. Higher Susceptibility of Hereford Hereford Other

32. Hereford – 22.4% Incidence

33. Is there a genetic component?

34. Estimates of Heritability Range 0.00 to 0.28

35. Over All Breeds Low to Moderate heritability

36. B. indicus vs B. taurus

38. Crossbred calves from tropically adapted sires had a significantly lower incidence of IBK

39. Bovine Respiratory Disease • Most common and costly disease of beef cattle, losses $400 - $600 million per year. • Commonly causes reduced weight gain from lack of appetite or inability to eat

42. Are there breed differences?

44. Is there a genetic component?

45. Over All Breeds Moderate genetic component to resistance to BRD

46. Does heterozygosity influence BRD?

47. Effect of Heterozygosity

48. Effect of Heterozygosity • Yes, crossbred cattle had significantly lower incidence of BRD compared to purebreds.

49. Bovine Respiratory Disease in Feedlot Cattle

50. Castration Dehorning Transport Diet Change Additive Distressors Weaning Immunity Challenge Sick