What do we know about genetics role in cattle diseases? Larry Kuehn Research Geneticist US Meat Animal Research Center

Genetics of disease Over 1,000,000 genetic tests at once! Human Diseases: Heart Attacks Cancer Diabetes Arthritis Contagious Diseases

Genetics of disease - people Main target of genetics in people Multi-billion dollar industry One of the main incentives for genomics work in people is for disease susceptibility May allow for tailored drugs

Do genetics explain everything? NO! Phenotypes (what we observe) = Genotypes (Genes coded in DNA) + Environment (Non-genetic factors) For example, contagious disease require exposure to pathogens –Vaccination, heart drugs, diet, exercise, location Genetics can indicate risk

Cattle diseases Typically most concerned about contagious/toxin diseases –Pinkeye –Foot rot –Mastitis (especially dairy cows) –Calf scours –Bloat –Respiratory disease complex –Leptospirosis, Blackleg, etc.

Why use genetic as a tool at all? Current suite of tools may not be sufficient –Vaccinations – animals still show signs of shipping fever High priority area of research that continues to improve –Antibiotics Don’t work on viral diseases Will we be able to use indefinitely? Concerns over bacterial adaptation Consumers may not want animals fed/injected with antibiotics

Is selection feasible? Can we identify animals that are more or less susceptible or at risk of acquiring a disease? Some success stories have been reported

Mastitis in dairy cattle Infection of mammary tissue –Decreased yield –Poorer milk quality –Early culling Can cost $100 to $200 per cow per lactation Greater problem as confinement of dairy cows increases Subclinical animals difficult to identify

USDA-ARS AIPL Mastitis in dairy cattle Animals with mastitis (even subclinical) have higher somatic cell counts Genetic evaluations (EPDs) for somatic cell count available in US since 1994

External parasites in sheep Nematodes in GI tract Severe loss of productivity –Often leads to death. Antihelmintic drugs losing effectiveness –Overuse in industry (multiple treatments) –Natural selection for resistance Young lambs particularly vulnerable

External parasites in sheep Direct measure of worm load not available Generally fecal egg count used as a proxy (number of worms/gram of feces) Substantial progress has been made –NZ selection line example Morris et al., 2007

Other diseases Upon examination in research populations –Generally low to moderately heritibable 5-25% of the variation observed is likely due to genetic factors. Family lines tend to show higher or lower incidence rates relative to whole population Suggests opportunity for permanent genetic change Diseases: Pinkeye, Tuberculosis, Brucellosis, Johne’s disease, Bovine Respiratory Disease

Where does that leave us? Incidence of several disease traits seems to be partially under genetic control Accurate measurement of disease incidence seems to be possible in research populations but would probably be much more difficult in industry We don’t know whether selection for disease resistance will be successful

Problems to be addressed Determine feasibility of selection for reduced disease risk –Use traditional selection methods and look for genomic (DNA marker) variation Identify measures beyond disease incidence to sort out subclinical and animals with high risks of disease USMARC using Bovine Respiratory Disease Complex (BRDC) as an initial model

Bovine respiratory disease complex Most costly disease to the cattle industry –97.6% of feedlots treat –14.4% of cattle are treated for symptoms –Accounts for over 50% of feedlot deaths –Cattle treated for BRDC expected to return at least $40 less than untreated calves NAHMS, 1999 Fulton et al., 2002

Wyeth Animal Health Bovine respiratory disease complex  Fever  Nasal discharge  Eye discharge  Decreased appetite  Depression/lethargy  Excessive salivation  Rapid/noisy breathing  Open mouth breathing  Droopy ears  Diarrhea  Death Clinical Symptoms: None are absolute

Some are relatively easy to diagnose… Cattle Treatment Guide, 2004 Cattle Disease Guide, 2001

Others are more difficult…

Causes of BRDC At least four primary viral agents –Parainfluenza-3 (PI 3 ) –Infection Bovine Rhinotracheitis (IBR) –Bovine Viral Diarrhea (BVD; 2 strains) –Bovine Respiratory Syncytial Virus (BRSV) Two primary bacterial causes –Mannheimia haemolytica (shipping fever) –Haemophilus somnus (brain fever)

Causes of BRDC Viral/bacterial agents vary widely in severity Secondary infections common M. haemolytica part of normal flora –Opportunistic pathogen –Stress/other infections trigger disease –Often observed in cattle 1-2 wks after arrival in a feedlot (i.e., shipping fever)

Loneragan, 2001 BRD epidemic curve

Increasingly important as cattle are shipped and mixed from multiple sources across the country

Identifying susceptibility with multiple phenotypes Example 1: Animal suffering with respiratory disease but missed diagnosis –Lung lesions, blood counts, ‘vital signs’, decreased performance (e.g., gain) Example 2: Susceptible animal with low exposure to pathogens –Immune response to vaccination (with or without imposed stress), correlations with regular production traits, stress response

Hierarchical approach to phenotypes Disease Resistance Population Feed Efficiency Population Other USMARC animals Commercial Feedlots Intensive phenotypingExpensive measuresInvasiveAnimal number

Potential solution Use genomic tools in research populations to export resistance to our seedstock Likely more animals and markers needed than initially thought USMARC and NBCEC project combination needed

Questions?