selecting for favorable genetic response to disease gary snowder, phd research geneticist usda, ars,...

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