No silver bullet to combat pig diseases: need for an integrated multidisciplinary approach. Pramod K. Mathur

Transcription

1 No silver bullet to combat pig diseases: need for an integrated multidisciplinary approach Pramod K. Mathur

2 No silver bullet to combat pig diseases: need for an integrated multidisciplinary approach Main messages Resistance to disease has sizable heritable component Specific SNPs and genes can make a significant contribution But multiple genes, multiple pathogens, multiple diseases Genetics can make its contribution but disease surveillance, biosecurity, vaccination are also important Need for an integrated approach by geneticist, immunologists, virologists and other disciplines

3 Resistance to disease has sizable heritable component Porcine Reproductive and Respiratory Syndrome (PRRS) N Heritability Viremia 21 (log) Virus load (AIC) WG21 (kg) WG42 (kg) ± ± ± ±0.14 Genetic Correlation ± 0.26 Adapted from Boddicker et al., 2012

4 Higher genetic variation is available during disease outbreaks for breeding and selection Number born alive Number dead pigs Healthy Disease Healthy Disease Additive genetic σ a Permanent Service S. σ l σ ss Residual σ r Total σ p h Mathur et al, 2014

5 Genomic regions: Chromosomes 4 and 7 Viral load Weight gain 15 % genetic variation 11 % genetic variation Adapted from Dekkers et al. 2014

6 QTN in GBP5 gene for PRRS G = Linked to unfavorable A allele T = Linked to favorable B allele

7 Gene editing for PRRS (CD163) Whitworth et al. (2015)

8 Gene editing for CD163 Some of the European PRRSV strains are capable of using receptors other than CD163 to enter the cell (Fabriek et al.,2009, Blood 113: ) Gene editing of one zygote is easy, but gene-editing an entire population is both costly and complex No natural variation, most likely recessive mode of inheritance Large number of edits Need to control inbreeding Avoiding unfavorable effects on resistance to other diseases and economic traits Difficulty in getting acceptance from government regulators and public

9 Multiple genes, pathogens, diseases, control measures Inheritance of most diseases is considered polygenic Need to breed for more than diseases Genetics can make significant contributions but heritabilities for most disease traits are just moderate (below 50%) Complete eradication requires combination with biosecurity and other disease control measures

10 Genomics to matabolonomics Genomics Transcriptomics Proteomics Metabolonomics

11 Matabolonomics to genomics Action Metabolomics= What is actually happening Proteomics Transcriptomics Genomics= What is supposed to happen Intention Source: Elda Dervishi, U. of Alberta

12 Virology, statistical modeling and genomics Function to fit individual viremia data profiles Raw PRRS viremia data Predicted viremia (extended Woods model predictions) Islam et al., PLoS ONE 2012

13 A more realistic, process based model Model of within host dynamics in the lung The model synthesizes existing literature findings on immune response to PRRSV infection Go et al., PLoS ONE 2014

14 The process based model can reproduce the wide range of observed viraemia profiles

15 Combination of genetics and vaccination for PRRS Vaccinated for PRRS using Ingelvac MLV vaccine Vaccine ADG (Kg/day) AA AB Non-Vx AA ** Vx AB Vaccine Viral Load AA ** Vx * ** *** AB P < 0.1 P < 0.05 P < Dunkelberger et al. (2016)

16 Combination of genetics and vaccination for PRRS and PCV2 Infection with field PRRS strain (KS62) and field PCV2 strain Vaccinated using Ingelvac MLV, heterologous to field PRRS strain a AA b AB PRRS Viral Load Vaccine ready pigs! c AA d AB 50 Non-Vx Vx Dunkelberger et al. (2016)

17 Also combination of genetics and treatment: Personalized medicine! Source: Paving the Way for Personalized Medicine: FDA s Role in a New Era of Medical Product Development, October 2013

18 Partnership for pre-competitive research Research topics directly related to pig breeding WP 12: Age-dependent immune response WP 13: Genetics and biomarkers for immune response WP16: Prediction models to determine the impact of vaccination on disease epidemiology and pathogen evolution

19 Partnership for pre-competitive research

20 Concluding remarks Genetics can make a significant contribution to reducing the risks of important diseases in pigs However, a single measure is not enough for effective control and eradication of most endemic diseases An integrated multidisciplinary approach is necessary for effective control and eradication measures

21 Thank you!