Genetics of PRRS in growing pigs Jack Dekkers
- Slides: 21
Genetics of PRRS in growing pigs Jack Dekkers Nick Boddicker Emily Waide Andrew Hess Iowa State University Bob Rowland Kansas State University Joan Lunney USDA-ARS Graham Plastow University of Alberta
60 K SNP chip Illumina 2007 Objective Use genomics to identify genes / genomic regions associated with resistance / susceptibility to PRRS virus infection Led by Joan Lunney – USDA – ARS Beltsville Bob Rowland – Kansas State University Jim Reecy – Iowa State University Jack Dekkers – Iowa State University Strong Industry Participation PHGC Breeding Companies Fast Genetics, Genesus, Choice Genetics PIC/Genus, TOPIGS, Pig. Gen Canada
Nursery Pig Challenge Model R. Rowland et al. , Kansas State University Groups of ~200 commercial crossbred pigs infected with PRRS virus isolate NVSL 97 -7985 between 18 and 28 d of age Acclimation Day post infection -7 Birth 0 4 Serum Weight Antibiotics Serum Inoculation 7 11 Weight Serum 14 21 28 35 Weight Serum Serum 42 Weight Serum Slaughter Ear for DNA
Host Response Phenotypes Log(viremia) Body weight h 2 = 0. 41 h 2 = 0. 29 Rebound rp = -0. 25 rg = -0. 47 Viral Load Area Under Curve
First Generation PHGC trials Boddicker et al. J. Anim. Sci. 2012, Animal Genetics 2014, Genetics Selection Evolution 2014 Trial PHGC 13 PHGC 4 PHGC 5 PHGC 6 PHGC 7 PHGC 8 Parents Parental Breeds Sires LW Dams LR Sires Duroc Dams LW/LR comp Sires Duroc Dams LR/LW comp Sires LR Dams LR Sires Pietran Dams LW/LR comp Sires Duroc Dams Y/LR # piglets Sex 562 All Barrows 195 Barrows + gilts 199 Barrows + gilts 198 All Barrows 197 Barrows + gilts 200 Barrows + gilts
Results of Genomic Analyses Viral Load Chr 4 1 Mb region explains 15% of genetic variance Includes important candidate genes GBP 1 GBP 2 GBP 5 GTF 2 B PKN 2 Weight Gain Chr 4 11% of genetic variance
Effects of WUR 10000125 on Viral Load Trials 1 -8 WUR genotype AA AB 115 BB ab a 110 a a b b b 105 a a b a ab n=158 n=29 5 Trial n=87 n=85 n=22 n=124 n=57 n=3 4 n=112 n=11 n=163 n=28 n=4 100 n=376 n=139 n=15 b n=1023 n=347 n=44 Virus Load (area under the curve) 120 95 1 -8 1 -3 Boddicker et al. 2012, 2014 a, b 6 7 8 MAF = 0. 17
Effects of WUR 10000125 on Weight Gain Trials 1 -8 28 WUR genotype AA AB BB ab ab a b b ab a a a b a n=161 n=28 n=4 n=122 n=58 n=3 1 -3 4 5 Trial n=87 n=85 n=22 n=362 n=137 n=14 All n=95 n=11 n=983 n=345 n=43 13 n=156 n=26 Weight Gain (kg) 23 18 b b b 8 Boddicker et al. 2012, 2014 a, b 6 7 8
SSC 4 region effects over time PHGC 1 -8 7 Viremia (Log 10 Templates/ml, q. PCR) P=3*10 -7 1*10 -9 1*10 -16 9*10 -12 6 5 2*10 -6 AA 4 AB 3 7*10 -4 2 0. 07 1 0 0 5 10 Boddicker et al. 2012, 2014 a, b 15 20 25 Days Post Infection 30 35 40
SSC 4 region effects over time PHGC 1 -8 7 25 1*10 -9 1*10 -16 9*10 -12 6 6*10 -9 20 5 2*10 -6 2*10 -8 AA 4 15 3 AB 7*10 -4 3*10 -7 2 0. 07 10 0. 01 1 0 5 10 Boddicker et al. 2012, 2014 a, b 15 20 25 Days Post Infection 30 35 40 Weight (kg) Viremia (Log 10 Templates/ml, q. PCR) P=3*10 -7
Generation 1 & 2 PRRS trials Trial Number n Breed PRRSv Isolate 1 -3 530 LW x LR 4 195 Duroc x LW/LR 5 184 Duroc x LR/LW 6 123 LR x LR 7 194 Pietran x LW/LR 8 188 Duroc x LW/LR 15 184 LR x LW 10 176 LR x LW 11 176 LW x LR 12 174 LR x LW 14 180 Duroc x LR/LW NVSL KS 06 Total 2304 challenged pigs with deep phenotypes
A major QTL for host response to PRRS on SSC 4 Boddicker et al. 2012, 2014 a, b; Hess et al. 2015 VIRAL LOAD WEIGHT GAIN
A major QTL for host response to PRRS on SSC 4 Hess et al. 2015 rg(VL) = 0. 86 (+0. 19) Viremia NVSL AA Viremia NVSL AB 7 6 6 5 5 4 3 2 2 1 1 0 0 5 10 15 20 25 30 Days Post Infection Viremia KS 06 AB 7 Log 10(Viremia) Viremia KS 06 AA 35 40 0 0 5 10 15 20 25 30 Days Post Infection 35 40
A major QTL for host response to PRRS on SSC 4 Hess et al. 2015 rg(VL) = 0. 86 (+0. 19) rg(WG) = 0. 86 (+0. 27) Viremia NVSL AA Viremia KS 06 AA Viremia NVSL AB 25 Weight NVSL AB 7 6 6 5 15 3 10 2 Log 10(Viremia) 20 Weight (kg) Log 10(Viremia) 20 4 25 5 15 4 3 10 2 5 1 0 0 0 5 10 15 20 25 30 Days Post Infection 35 40 Weight (kg) Weight NVSL AA 7 Viremia KS 06 AB Weight KS 06 AA Weight KS 06 AB
Identification of other host response QTL Waide et al. KS 06 NVSL WUR == 77 WUR = 21 Viral Load rg(NVSL, KS 06) = 0. 86 (+0. 19) Genomic regions do not overlap between PRRSV isolates But pathways do
Identification of other host response QTL Weight Gain KS 06 NVSL WUR == 16 16 rg(NVSL, KS 06) = 0. 86 (+0. 27)
Genomic Prediction using high-density SNPs Meuwissen et al. 2001 Training population Phenotypes SNP Genotypes Selection candidates SNP Genotypes Estimate SNP effects Genomic Prediction
Can we use Genomic Prediction across isolates? NVSL Trials r/h KS 06 Trials KS 06 NVSL 19
Conclusions q q q Piglet response to experimental PRRSv challenge has a sizeable genetic component. Chromosome 4 contains a major gene for host response to PRRSv in growing piglets. Genetic selection for improved host response to PRRS is possible and can be an important component in the fight against PRRS
Evolution of PRRS Host Genetics Research 1. Experimental infection of nursery pigs with a specific PRRSV strain 2. Experimental infection of nursery pigs with another PRRSV strain 3. Experimental co-infection of nursery pigs: PRRS + PCV 2 (incl. PRRS vaccination) 4. Field trials
Scientific Collaborators Iowa State University Thanks to all Partners Nick Boddicker Andrew Hess Emily Waide Chris Eisley Jenelle Dunkelberger James Koltes Eric Fritz-Waters Martine Schroyen Nick Serao Jim Reecy Chris Tuggle Susan Carpenter Kansas State University Bob Rowland PRRS group Ben Trible Megan Niederwerder Maureen Kerrigan Becky Eaves et al USDA-ARS Joan Lunney group Igseo Choi Sam Abrams Funding Industry Partners University of Alberta Graham Plastow group Univ. Saskatchewan John Harding group Roslin Institute Steve Bishop Andrea Doeschl-Wilson Zeenath Islam Graham Lough Univ. Minnesota Monserat Torremorrell NIFA