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)
The problem is measuring WITHIN BREED differences for disease resistance.

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:
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
The problem is measuring WITHIN BREED differences for disease resistance.
Atrophic rhinitis (AR) is a widely prevalent, multifactorial disease of swine characterized by a degeneration and/or failure of growth of the nasal turbinate bones. Clinical signs include sneezing, nasal discharge or bleeding, and distortions of the snout.
The milder, nonprogressive form of AR is caused by a toxin- producing bacterium, Bordetella bronchiseptica. The more severe and progressive form is caused by the toxin-producing Pasteurella multocida bacterium, alone or in combination with other bacteria such as Bordetella bronchiseptica. The severity of the disease may be related to the age of the pig when infected, the dose of infectious organisms, the amount of toxin produced by the bacteria and environmental conditions.
Source:

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.
Except for the nervous system, the immune system is the most complex biological system.

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.
Selection for growth is associated with physiological diseases (joints, bones).
Solution: total merit index of production and disease traits

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

15. Challenges ● Many factors influence disease resistance. nutrition age
genetics
stress
mgmt system
biological status
pathogen(s)
season
immune system
immunological background
epidemiology
etc…..

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:
Viruses Infectious 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)
Secondary disease – blood sucking lice in cattle reduce immune system making the animal more susceptible to a secondary disease such as pneumonia or scours..

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
Somatic Cell Score .15
Pinkeye
Respiratory to .48
Estimate of variation due to additive effects of genes.

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

25. Infectious bovine keratoconjunctivitis (IBK), pinkeye
Introduction
Infectious bovine keratoconjunctivitis (IBK), pinkeye
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. Incidence of IBK by Date
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?

30. Overall 41,986 123 Group N Age detected, d Incidence, % Angus 6,347
155
3.7
Hereford
4,579
112
22.4
Red Poll
998
120
3.1
Charolais
2,878
137
6.5
Simmental
1,775
121
7.6
Limousin
961
128
3.4
Gelbvieh
2,391
135
2.1
Pinzgauer
908
1.3
Braunvieh
907
139
1.8
MARC I
4,336
131
3.9
MARC II
4,959
132
MARC III
10,947
118
5.9
Overall
41,986
123

31. Higher Susceptibility of Hereford
Other

32. Hereford – 22.4% Incidence

33. Is there a genetic component?

34. Estimates of Heritability
Breed h2
Angus
0.25 ± 0.04
Hereford
0.28 ± 0.05
Red Poll
0.09 ± 0.10
Charolais
0.00 ± 0.02
Simmental
0.08 ± 0.04
Limousin
0.11 ± 0.10
Gelbvieh
0.05 ± 0.03
Pinzgauer
0.09 ± 0.08
Braunvieh
0.00 ± 0.06
MARC I
0.09 ± 0.03
MARC II
0.13 ± 0.03
MARC III
0.26 ± 0.04
Range 0.00 to 0.28

35. Over All Breeds
h2 = 0.22 ± 0.02
Low to Moderate heritability

36. B. indicus vs B. taurus

37. Germplasm N
Incidence
Hereford
137
33.6
Angus
286
2.1
MARC III
399
9.3
Hereford/Angus
138
2.2
Angus/Hereford 65
4.6
Hereford/MARC III
192
12.5
Angus/MARC III
247
8.9
Brahman/Hereford 61
0.0
Boran/Hereford
1.5
Tuli/Hereford 64
1.6
Brahman/Angus
Boran/Angus
144
Tuli/Angus
150
1.3
Brahman/MARC III
227
Boran/MARC III
237
0.4
Tuli/MARC III
275

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?

43. Group N
Age, d
Incidence
Mor-
tality
Total
death
Angus
6,347
111 10 14
1.4
Hereford
4,579
107 8 12
1.0
Red Poll
998
103 9 16
1.5
Charolais
2,878 87
1.7
Simmental
1,775 68 11 18
1.9
Limousin
961 88 7
0.8
Gelbvieh
2,391
106
Pinzgauer
908 80
1.6
Braunvieh
907 19
1.8
MARC I
4,336
104 17
MARC II
4,959
MARC III
10,947 99
Overall
41,986
101

44. Is there a genetic component?

45. Moderate genetic component to resistance to BRD
Over All Breeds
h2 = ± .01
Moderate genetic component to resistance to BRD

46. Does heterozygosity
influence BRD?

47. Effect of Heterozygosity
Type N
British-British
27,944
British-Continental
36,390
British-Tropical
2,247
Cont-Continental
16,225
Cont-Tropical
2,166

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

49. Bovine Respiratory Disease in Feedlot Cattle

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

51. But, is there a genetic component to Bovine Respiratory Disease?

52. Data 18,112 cattle from 9 pure breeds and 3 composites
15 yr feedlot records ( )

53. Incidence of BRD by Year
Range: %; Avg. 17%

54. Days on Feed
Agrees with Loneragan (2001) and Schunicht et al. (2003)

55. Breed
Age, d
Incidence, %
Mortality, %
Total death, %
Angus
205
10.2
1.9
0.5
Hereford
206
18.5
4.5
0.9
Charolais
213
13.7
5.8
1.4
Gelbvieh
211
14.8
3.4
Red Poll
201
22.2
8.9
2.1
Simmental
190
33.2
4.4
1.7
Pinzgauer
200
35.0
1.2
Braunvieh
198
34.0
0.1
1.1
Limousin
32.3
3.7
MARC I
15.9
5.1
MARC II
196
18.8
3.1
MARC III
202
14.6
3.6
0.8
Overall
17.0
3.9
1.0

56. Heritability
0.18

57. Phenotypic, genetic, and environmental correlations with BRD
Trait
Pheno
Geno
Enviro
Live weight
0.08
0.14 ± 0.06
0.12 ± 0.01
ADG
0.11
0.08 ± 0.07
Fat thickness
0.04
-0.08 ± 0.15
0.07 ± 0.04
Marbling score
0.02
0.09 ± 0.13
0.00 ± 0.04
REA
-0.12 ± 0.15
0.06 ± 0.03
Retail cuts
-0.12 ± 0.13
0.11 ± 0.04
Fat trim
0.07
0.07 ± 0.13
0.08 ± 0.04
Shear force
0.00
0.20 ± 0.16
-0.04 ± 0.03
Tenderness
0.01
-0.16 ± 0.15
0.01 ± 0.03
Juiciness score
0.09 ± 0.17
-0.02 ± 0.03

58. Conclusions Research for disease resistance is
Highly complex
Of significant importance to consumers and product quality
Fairly new research area for genetics
Genetic variation within and across breeds for some diseases is present
A great deal more research must take place