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Learning to date and the way forward for genetics and swine health
Graham Plastow Breakout Session #6 Swine Health & Genomics
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Success Factors Leadership – shared vision Collaboration Recipe
Industry – Government – Academic National and International Recipe Genotype + phenotype = information
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Animals and Samples
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Breeding for “Disease Resistance”
Or reduced susceptibility Host Genetic Variation Identified For every type of pathogen Probably exists for all diseases Major opportunity for genomics As difficult and expensive to measure trait May be only practical way to breed healthier pigs
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Can It Be Done? Examples already exist
E.g. Resistance to E. coli F18, a major cause of bowel edema and one of the causes of post-weaning scours Single gene giving recessive resistance - the gene’s scientific name is FUT1 M307
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FUT1 M307 – Death loss ** P<0.001
Described in van der Steen, Prall, Plastow (2005) J. Anim. Sci. 83:E1-E8
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FUT1 M307 – Average Daily Gain
** P<0.001
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The PRRS Host Genetics Consortium (PHGC)
Understanding the role of host genetics in resistance to PRRSV infection, and the effects of PRRS on pig health and related growth. Uses a nursery pig model to assess pig resistance/ susceptibility to primary PRRSV infection. After acclimation, pigs infected with PRRSV and followed for 42 days post infection (dpi). Blood samples collected at 0, 4, 7, 10, 14, 21, 28, 35 and 42 dpi, and weekly weights recorded. Joan Lunney. USDA BARC Bob Rowland, KSU
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Weight distribution at different
Why PRRS? $700 million/yr in US Weight distribution at different times after infection Number Data from PHGC trial 1 (Rowland et al, unpublished data). Weight
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“Blood, a window into health…” Leroy Hood PAG 2009
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Finding the Causative Mutation amongst many candidate genes
Identified DE genes between genotypes (AA vs AG) 3 genes were DE: Only one was DE across multiple time points * ** *** NS
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A SNP introduces a new acceptor splice site, which causes five nucleotides to be added to the transcript The 5bp transcript causes a frame-shift in the protein that introduced an early stop codon. The susceptible genotype is missing the C-terminus of the protein Koltes et al. BMC Genomics 16:412.
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Studying variation in response to Salmonella
Why do some animals develop a carrier state and create a food safety hazard? Salmonella-free pigs were infected with S. Typhimurium on day 0 9-10 weeks old Observation: fecal bacteria over 20 days of experiment measured at 0, 2, 7, 14, and 20 days post inoculation Phenotype: Area under the curve of log-transformed counts from 0-20 days Tuggle et al see next slides
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Study “extreme” phenotypes
Uthe, J.J., et al. (2009) Vet. Micro. 135: Salmonella inoculation “Persistent Shedders” PS1, PS2 “Low Shedders” LS1, LS2
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Breeding for “Disease Resistance”
Rather the question is about the target Specific diseases or Improved “Robustness” or “Resilience”?
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Can It Be Done? Examples already exist
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A new example Nature Biotechnology 34, 20–22 (2016) doi: /nbt.3434 Published online 07 December 2015
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NVSL ,
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Breeding for “Disease Resistance”
Rather the question is about the target Specific diseases or Improved “Robustness” or “Resilience”?
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Breeding for “Disease Resistance”
Differentially expressed genes identified in three different environments Ye, Stothard, Plastow et al. unpublished results
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Partnership Large scale multidisciplinary projects are doable
Field data while non-ideal provides new insights and can increase confidence for application Technology advances mean that samples can increase in value over time
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Thanks! Agricultural Research Service USDA Pig Genome Coordinator
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Multi-dimensional comparison assessment of
Higher throughput vs. in-depth analysis of immune parameters Proximal vs. distal Local vs. systemic Short vs. long term Basal vs. immune-challenged Antimicrobial vs. homeostasis Blood WBCs Mesenteric lymph nodes Lung tissue Alveolar inflammatory cells Hematopoietic stem cells and progenitors Bone marrow macrophages Multi-dimensional comparison assessment of immune competence and inflammation Putting it all together – new Large Scale project led by Dyck, Harding……………………………
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