selecting for favorable genetic response to disease
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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
• 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
Justifications
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
Consumers expect meat animals raised with better welfare, produced in an environmentally friendly manner and,
free of feed “additives”, antibiotics, and vaccines.
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
Justification: Disease liability can be traced back to owner
Source: www.usaip.info
The immune system is The immune system is highly complex.highly complex.
Only the nervous system Only the nervous system is more complex.is more complex.
More complex than More complex than reproduction, growth, reproduction, growth, lactation, or feed lactation, or feed efficiency.efficiency.
• 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
Challenges
● Many factors influence disease resistance.
nutrition age genetics
stress mgmt system biological status
pathogen(s) season immune system
immunological background
epidemiology etc…..
• Difficult to identify phenotype for disease resistance.• False assumption that all healthy animals are disease
resistant.
Challenges
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)
• Some diseases are caused by a variety of microbes
Challenges
STRESS + PATHOGENS = DISEASEPATHOGENS + STRESS = DISEASEPATHOGENS + STRESS = DISEASE
So with some diseases we So with some diseases we might be better to select for might be better to select for
resistant to “stress”??resistant to “stress”??
Can we select for Can we select for genetic resistance to a genetic resistance to a
disease?disease?
Genetic research of human diseases, especially molecular genetics, is far ahead of livestock research.
Highly successful in plantsCorn
WheatOatsBean
Broccoli Cabbage Carrots
CucumberPeppers Tomato Melon
Squash
Genetically Resistance to:
FungiViruses
NematodesWilt
BlightLeafspotRoot rotSunspot
Disease Resistance is Heritable
Mastitis .02Somatic Cell Score .15Pinkeye .22Respiratory .11 to .48
Current research on the Current research on the influence of genetics on influence of genetics on resistance to BRD and resistance to BRD and
IBKIBK
Current research on the Current research on the influence of genetics on influence of genetics on resistance to BRD and resistance to BRD and
IBKIBK
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)
Introduction
0
5
10
15
20
25
30
1983 1986 1989 1992 1995 1998 2001
Year
Inci
denc
e
Incidence of IBK across years
Mar20 Apr19 May19 June18 July18 Aug17 Sept16 Oct16
Incidence of IBK by Date
Most common bacterial pathogen is Moraxella bovis
Group NAge
detected, dIncidence, %
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 908 121 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
Overall 41,986 123 6.5
0
10
20
30
40
50
60
70
1983 1986 1989 1992 1995 1998 2001
Year
Inci
denc
eHigher Susceptibility of Hereford
Hereford
Other
Hereford – 22.4% Incidence
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
Estimates of Heritability
Range 0.00 to 0.28
h2 = 0.22 ± 0.02
Over All Breeds
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
0
5
10
15
20
25
1983 1985 1987 1989 1991 1993 1995 1997 1999 2001
YEARS
PE
RC
EN
T S
ICK
INCIDENCE OF BRD BY DAY OF AGE (1983 - 2002)
05
1015202530354045
0 21 42 63 84 105 126 147 168 189 210 231
DAYS OF AGE
NO
. OF
CA
LVE
S
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 12 14 1.7
Simmental 1,775 68 11 18 1.9
Limousin 961 88 12 7 0.8
Gelbvieh 2,391 106 10 10 1.0
Pinzgauer 908 80 11 16 1.6
Braunvieh 907 88 19 9 1.8
MARC I 4,336 104 17 10 1.7
MARC II 4,959 104 9 12 1.0
MARC III 10,947 99 10 17 1.7
Overall 41,986 101 11 12 1.4
Over All Breeds
h2 = 0 .22 ± .01
Moderate genetic component to Moderate genetic component to resistance to BRDresistance 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 Bovine Respiratory Disease in Feedlot CattleFeedlot Cattle
WeaningImmuni
ty
Challenge
Diet Change
Castration
Dehorning Transpor
t
Additive DistressorsAdditive Distressors
Sick
But, is there a genetic component to But, is there a genetic component to Bovine Respiratory Disease?Bovine Respiratory Disease?
Data
• 18,112 cattle from 9 pure breeds and 3 composites
• 15 yr feedlot records (1987-2001)
0%
10%
20%
30%
40%
50%
1987 1989 1991 1993 1995 1997 1999 2001
Year
Inci
denc
eIncidence of BRD by Year
Range: 5 - 44%; Avg. 17%
Days on Feed
0
10
20
30
40
50
60
70
80
90
100
0 20 40 60 80 100 120 140 160 180 200
Days on feed
No.
Agrees with Loneragan (2001) and Schunicht et al. (2003)
Breed Age, dIncidence,
%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
HeritabilityHeritability
0.18
Phenotypic, genetic, and environmental Phenotypic, genetic, and environmental correlations with BRDcorrelations 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 0.12 ± 0.01
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 0.02 -0.12 ± 0.15 0.06 ± 0.03
Retail cuts 0.04 -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 0.00 0.09 ± 0.17 -0.02 ± 0.03
ConclusionsConclusions
• 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