Transcript Slide 1

Selecting for Favorable
Genetic Response to
Disease
Gary Snowder, PhD
Research Geneticist
USDA, ARS, USMARC
Outline
• Justification
• Challenges
• Current research on Genetic
Resistance to BRD and IBK
Justifications for
Genetic Selection
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
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
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)
Justifications
• New consumer expectations
– Meat free of drug residue
– Meat animals live a healthy and happy life
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.
Justification: Disease liability can be traced
back to owner
Source: www.usaip.info
The immune system is
highly complex.
Only the nervous system
is more complex.
More complex than
reproduction, growth,
lactation, or feed
efficiency.
Challenges
• Selection for animals resistant to a particular
pathogen may
• make that pathogen more virulent,
• make the host more susceptible to another microbe
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.
Challenges
Microbes can change their genetic make-up
faster than livestock.
Challenges
● Many factors influence disease resistance.
nutrition
stress
pathogen(s)
immunological
background
age
genetics
mgmt system
biological status
season
immune system
epidemiology
etc…..
Challenges
• Difficult to identify phenotype for disease resistance.
• False assumption that all healthy animals are disease
resistant.
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)
STRESS + PATHOGENS =
PATHOGENS + STRESS = DISEASE
DISEASE
So with some diseases we might be better
to select for resistant to “stress”??
Can we select for
genetic resistance to a
disease?
Genetic research of
human diseases,
especially molecular
genetics, is far ahead of
livestock research.
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
Disease Resistance is Heritable
Mastitis
Somatic Cell Score
Pinkeye
Respiratory
.02
.15
.22
.11 to .48
Current research on the
influence of genetics on
resistance to BRD and
IBK
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)
30
25
Incidence
20
15
10
5
0
1983
1986
1989
1992
Year
1995
1998
Incidence of IBK across years
2001
Mar20
Apr19
May19 June18 July18 Aug17 Sept16
Incidence of IBK by Date
Oct16
Most common bacterial
pathogen is Moraxella
bovis
Age
detected, d
Incidence, %
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
121
1.3
Braunvieh
907
139
1.8
MARC I
4,336
131
3.9
MARC II
4,959
132
3.7
MARC III
10,947
118
5.9
123
6.5
Group
N
Angus
Overall
41,986
Higher Susceptibility of Hereford
Hereford
Other
Hereford – 22.4% Incidence
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
Over All Breeds
h2 = 0.22 ± 0.02
Low to Moderate heritability
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
65
1.5
Tuli/Hereford
64
1.6
Brahman/Angus
138
2.2
Boran/Angus
144
0.0
Tuli/Angus
150
1.3
Brahman/MARC III
227
0.0
Boran/MARC III
237
0.4
Tuli/MARC III
275
2.2
Crossbred calves from tropically
adapted sires had a significantly
lower incidence of IBK
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
ANNUAL INCIDENCE OF BRD
25
PERCENT SICK
20
15
10
5
0
1983
1985
1987
1989
1991
1993
YEARS
1995
1997
1999
2001
NO. OF CALVES
INCIDENCE OF BRD BY DAY OF AGE
(1983 - 2002)
45
40
35
30
25
20
15
10
5
0
0
21
42
63
84 105 126 147 168 189 210 231
DAYS OF AGE
Angus
Hereford
Red Poll
6,347
4,579
998
111
107
103
10
8
9
Mortality
14
12
16
Charolais
Simmental
Limousin
2,878
1,775
961
87
68
88
12
11
12
14
18
7
1.7
1.9
0.8
Gelbvieh
Pinzgauer
Braunvieh
MARC I
2,391
908
907
4,336
106
80
88
104
10
11
19
17
10
16
9
10
1.0
1.6
1.8
1.7
MARC II
MARC III
4,959
10,947
104
99
9
10
12
17
1.0
1.7
Overall
41,986
101
11
12
1.4
Group
N
Age, d Incidence
Total
death
1.4
1.0
1.5
Over All Breeds
h2 = 0 .22 ± .01
Moderate genetic component to
resistance to BRD
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
Effect of Heterozygosity
• Yes, crossbred cattle had significantly
lower incidence of BRD compared to
purebreds.
Bovine Respiratory Disease in Feedlot
Cattle
Additive Distressors
Weaning
Immunity
Castration
Dehorning
Transport
Diet Change
Challenge
Sick
But, is there a genetic component to
Bovine Respiratory Disease?
Data
• 18,112 cattle from 9 pure breeds and 3
composites
• 15 yr feedlot records (1987-2001)
Incidence of BRD by Year
50%
Incidence
40%
Range: 5 - 44%; Avg. 17%
30%
20%
10%
0%
1987
1989
1991
1993
1995
Year
1997
1999
2001
No.
Days on Feed
Agrees with Loneragan (2001) and Schunicht et al. (2003)
100
90
80
70
60
50
40
30
20
10
0
0
20
40
60
80
100
120
Days on feed
140
160
180
200
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
0.9
Red Poll
201
22.2
8.9
2.1
Simmental
190
33.2
4.4
1.7
Pinzgauer
200
35.0
3.4
1.2
Braunvieh
198
34.0
0.1
1.1
Limousin
190
32.3
3.7
1.4
MARC I
201
15.9
5.1
1.1
MARC II
196
18.8
3.1
0.9
MARC III
202
14.6
3.6
0.8
Overall
202
17.0
3.9
1.0
Heritability
0.18
Phenotypic, genetic, and environmental
correlations with BRD
Trait
Live weight
Pheno
0.08
Geno
0.14 ± 0.06
Enviro
0.12 ± 0.01
ADG
Fat thickness
Marbling score
0.11
0.04
0.02
0.08 ± 0.07
-0.08 ± 0.15
0.09 ± 0.13
0.12 ± 0.01
0.07 ± 0.04
0.00 ± 0.04
REA
Retail cuts
Fat trim
0.02
0.04
0.07
-0.12 ± 0.15
-0.12 ± 0.13
0.07 ± 0.13
0.06 ± 0.03
0.11 ± 0.04
0.08 ± 0.04
Shear force
Tenderness
Juiciness score
0.00
0.01
0.00
0.20 ± 0.16
-0.16 ± 0.15
0.09 ± 0.17
-0.04 ± 0.03
0.01 ± 0.03
-0.02 ± 0.03
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