dr. jack dekkers - genetics of host resistance to prrs and pcv2
TRANSCRIPT
Genetics of Host Resistanceto PRRS and PCV2
Jack Dekkers
Department of Animal ScienceIowa State University
Porcine Reproductive and Respiratory Syndrome - PRRS
Sows Abortions Stillborn/weak pigs Delayed estrus Respiratory
problems
Grower Increased
mortality Decreased
production Respiratory
problems
Large financial loss in both production settings
Respig.com Respig.com
Eradication Biosecurity Vaccination Host genetics
Strategies tocontrol PRRS
ObjectiveUse genomics to identify genes / genomic regions associated with
resistance / susceptibility to PRRS virus infection
Led byJoan Lunney – USDA – ARS Beltsville
Bob Rowland – Kansas State UniversityJim Reecy & Jack Dekkers – Iowa State University
Strong Industry ParticipationPHGC Breeding Companies
Fast Genetics, Genesus, Choice GeneticsPIC/Genus, TOPIGS, PigGen Canada
60 k SNP chipIllumina
GeneSeek2007
Iowa State UniversityNick Boddicker Andrew Hess Emily Waide,
Jenelle Dunkelberger Eric Fritz-WatersJames Koltes, Martine Schroyen Nick SeraoJim Reecy Chris Tuggle Susan Carpenter
Kansas State UniversityBob Rowland PRRS group
Ben Trible, Megan Niederwerder Maureen KerriganUSDA-ARS
Joan Lunney group, Igseo Choi, Sam AbramsUniversity of AlbertaGraham Plastow groupUniv. SaskatchewanJohn Harding group
Roslin InstituteSteve Bishop Andrea Doeschl-Wilson
Zeenath Islam Graham LoughUniv. Minnesota
Monserat Torremorrell, Bob Morrison
Scientific Collaborators
Integrated International Interdisciplinary Projects
Nursery PigChallenge Model
WeightSerum
SlaughterEar for DNA
-7 0 7 11 14 21 35 424 28
SerumAntibiotics
Acclimation
Birth WeightSerum
Inoculation
WeightSerum
WeightSerum
WeightSerum
WeightSerum
WeightSerum
Serum Serum
Day post infection
R.R.R. Rowland et al., Kansas State UniversityGroups of ~200 commercial crossbred pigs infected with
PRRS virus isolate NVSL97-7985 between 18 and 28 d of age
2304 challenged pigs with deep phenotypes
and genotypes
PHGC PRRS trialsGeneration 1 & 2
Host ResponsePhenotypes
Body weight Log(viremia)
Rebound
Viral LoadArea Under Curve
h2 = 0.41h2 = 0.29rp = -0.25 rg = -0.47
VIRAL LOAD WEIGHT GAIN
Major QTL for host response to PRRS on SSC 4
Boddicker et al. 2012, 2014a,b; Hess et al. 2015
0 5 10 15 20 25 30 35 400
1
2
3
4
5
6
7
Viremia NVSL AA
Viremia NVSL AB
Days Post Infection
Log
10(V
irem
ia)
0 5 10 15 20 25 30 35 400
1
2
3
4
5
6
7
Viremia KS06 AA
Viremia KS06 AB
Days Post InfectionL
og10
(Vir
emia
)
Hess et al. 2015
Major QTL for host response to PRRS on SSC 4
0 5 10 15 20 25 30 35 400
1
2
3
4
5
6
7
0
5
10
15
20
25
Viremia NVSL AAViremia NVSL ABWeight NVSL AAWeight NVSL AB
Days Post Infection
Log
10(V
irem
ia)
Wei
ght (
kg)
0 5 10 15 20 25 30 35 400
1
2
3
4
5
6
7
0
5
10
15
20
25
Viremia KS06 AAViremia KS06 ABWeight KS06 AAWeight KS06 AB
Days Post InfectionL
og10
(Vir
emia
)
Wei
ght (
kg)
Hess et al. 2015
Major QTL for host response to PRRS on SSC 4
AA pigs Truncated GBP5 protein PI3K-Akt pathway not turned off
See Poster by Martine Schroyen et al.A Hypothesis
Genomic regions do not overlap between isolates but GO-term pathways do
KS06
NVSL WUR = 21
WUR = 7WUR = 7
WUR = 21
See Poster by Emily Waide et al.
Identification of otherhost response QTL
Viral Load
rg(NVSL, KS06) = 0.86 (+0.19)
KS06
NVSL WUR = 16WUR = 16
Weight Gain
rg(NVSL, KS06) = 0.86 (+0.27)
See Poster by Emily Waide et al.
Identification of otherhost response QTL
Estimate SNP
effectsSNPGenotypes
Phenotypes
SNPGenotypes
Genomic Prediction
Training population
Validation population
PhenotypesCorrelate
Genomic PredictionPrediction using high-density SNPs
KS06 NVSL
Can we use GenomicPrediction across isolates?NVSL Trials
KS06 Trials
17
r/h
Waide et al. 2015
Total PRRS Antibody Responseat day 42
MHC Class I
MHC Class II
Two SNPs in MHC explain 15 and 30% of genetic varianceNo association with WUR SNP on SSC4
h2 = 13%
(Hess, Trible et al.)
NVSL KS060.4
0.6
0.8
1
1.2Cleared Rebound Persistent
S:P
ratio a b a a
ba
Relationship of PRRS Ab at 42 dpiwith serum viremia profiles
Hess et al. 2014
5 10 15 20 25 30 35 40-1
-0.6
-0.2
0.2
0.6
1
Days Post Infection
NVSL Viremia
5 10 15 20 25 30 35 40-1
-0.6
-0.2
0.2
0.6
1
Days Post Infection
KS06 Viremia
5 10 15 20 25 30 35 40-1
-0.6
-0.2
0.2
0.6
1
Days Post Infection
NVSL Weight Gain
5 10 15 20 25 30 35 40-1
-0.6
-0.2
0.2
0.6
1
Days Post Infection
KS06 Weight Gain
Phenotypic corr.Genetic correlation
Correlations of S:P at 42 dpi with viremia and weight gain (Andrew Hess)
See Poster by Andrew Hess
Association of Tonsil viremiawith serum viremial profile
Jack Dekkers, Chris TuggleJim Reecy, Ken Stalder
Robert RowlandYongming Sang
Joan LunneyMontse Torremorell
Robert MorrisonSteve Bishop, David Hume
Andrea Doeschl-Wilson
Translational Genomics USDA-NIFA grant # 2013-68004-20362
3rd Generation PRRS Challenge StudiesCo-infection and Field Studies
Genetically Improving Resistance of Pigsto PRRS Virus Infections
Translational Genomics USDA-NIFA grant # 2013-68004-20362
Outreach Obj. 3Education Obj. 4
Educate industry stakeholders and next generation of industry leaders
Arr
ive
Vacc
i-na
te
Days postvaccination -1 0 4 7 11 14 21 28 32 35 39 42 49 56 63 70
Days post infection 0 4 7 11 14 21 28 35 42
Infe
ct
Vaccination response Vaccination + infection responseEarly response Later response
Body weight and Blood samples
80k SNPgenotypes
Obj.1 Vaccination & Co-infection TrialsExperimental design
4 groups of 200 commercial crossbred piglets (18-21 d)
50 AA Vaccinated (PRRS MLV) 50 AB50 AA Non-vaccinated 50 AB
WUR WUR
Co-infection with PRRSv and PCV2 PCVAD
Seru
m
Days post 0 7 14 21 28 42 60 90 Market arrival
FMIA and SNA
Seru
mSe
rum
Seru
m
Seru
m
Wei
ght
Wei
ght
Wei
ght
Wei
ght
BF,
LEA
Body weightPen oral fluids for disease surveillance purposes on all days indicated
SNA on all oral fluid samples
29
Obj.2 Field Challenge Trials Experimental design
6 groups of 200 commercial crossbred piglets (18-21 d)
100 AA 100 ABWUR WUR
Moved into health-challenged barns
SNPgenotypes
PrePRRS VL
PRRS VL
Pre ADG
Post ADG
PCV2b VL
___ = AA Non Vx___ = AB Non Vx___ = AA Vx___ = AB Vx
Co-
infe
ctio
n
PRRS viremia
Co-
infe
ctio
nC
o-in
fect
ion Body weight PCV2b viremia
Results 2 co-infection Trials
Vacc
inat
ion
Vacc
inat
ion
See Poster by Jenelle Dunkelberger et al.
PrePRRS VL
PRRS VL
Post ADG
Co-
infe
ctio
n
PRRS viremia
Co-
infe
ctio
n
PCV2b VL
Vacc
inat
ion
Pre ADG
Co-
infe
ctio
n
Vacc
inat
ion
___ = AA Non Vx___ = AB Non Vx___ = AA Vx___ = AB Vx
Results 2 co-infection Trials
PrePRRS VL
PRRS VL
Post ADG
PCV2b VL
Co-
infe
ctio
n
Co-
infe
ctio
n Results 2 co-infection Trials
Vacc
inat
ion
Pre ADG
Co-
infe
ctio
n
Vacc
inat
ion
6 0 8 0 1 0 0 1 2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
f(x) = 0.2534995727812 x + 31.456703872604R² = 0.0713522979744744
Pre-Infection
Post
-Infe
c-tio
n
Post- vs. Pre-PRRS VL
Dunkelberger (2015)
33
8,74 16,86
2,284,139
(WUR) 7,24(MHC)
4,1367,40 12,4
Genome Wide Association Studies
See poster Jenelle Dunkelberger
Conclusions• Vaccination-co-infection design is good model for PCVAD • PRRSV vaccination amplification of PCVAD reduced growth• SSC4 QTL had a larger effect on PRRS viremia with
primary exposure to PRRS innate immune function.• SSC4 QTL affected PCV2b viremia but only after PRRS
vaccination• PRRS and PCV2b viremia controlled by different
genomic regions with versus without vaccination.
opportunities to select vaccine-ready pigs?
May 23-27, 2016, Iowa State University
Dr. Andrea Doeschl-Wilson, Univ. Edinburgh2014 course
Disease Genetics: From Concepts to UtilizationProf. Steve Bishop, Univ. Edinburgh
Disease Genetics Short CourseMathematical modelling of Infection Dynamics
Iowa State UniversityNick Boddicker Andrew Hess Emily Waide,
Jenelle Dunkelberger Eric Fritz-WatersJames Koltes, Martine Schroyen Nick SeraoJim Reecy Chris Tuggle Susan Carpenter
Kansas State UniversityBob Rowland PRRS group
Ben Trible, Megan Niederwerder Maureen KerriganUSDA-ARS
Joan Lunney group, Igseo Choi, Sam AbramsUniversity of AlbertaGraham Plastow groupUniv. SaskatchewanJohn Harding group
Roslin InstituteSteve Bishop Andrea Doeschl-Wilson
Zeenath Islam Graham LoughUniv. Minnesota
Monserat Torremorrell, Bob Morrison
Scientific Collaborators