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

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 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: www.usaip.info

Challenges

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.

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

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

Challenges ● Many factors influence disease resistance. nutrition age genetics stress mgmt system biological status pathogen(s) season immune system immunological background 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) Secondary disease – blood sucking lice in cattle reduce immune system making the animal more susceptible to a secondary disease such as pneumonia or scours..

STRESS + PATHOGENS = DISEASE PATHOGENS + STRESS = 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 .02 Somatic Cell Score .15 Pinkeye .22 Respiratory .11 to .48 Estimate of variation due to additive effects of genes.

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

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)

Incidence of IBK across years

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

Most common bacterial pathogen is Moraxella bovis

Are there breed differences?

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

Higher Susceptibility of Hereford Other

Hereford – 22.4% Incidence

Is there a genetic component?

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

B. indicus vs B. taurus

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

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

Are there breed differences?

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

Is there a genetic component?

Moderate genetic component to resistance to BRD Over All Breeds h2 = 0 .22 ± .01 Moderate genetic component to resistance to BRD

Does heterozygosity influence 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 Diet Change Castration Dehorning Transport 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 Range: 5 - 44%; Avg. 17%

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

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

Heritability 0.18

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

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