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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
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, PigGen Canada
60K SNP chip Illumina
2007
Nursery Pig Challenge Model
Weight Serum
Slaughter Ear for
DNA
-7 0 7 11 14 21 35 42 4 28
Serum Antibiotics
Acclimation
Birth Weight Serum
Inoculation
Weight Serum
Weight Serum
Weight Serum
Weight Serum
Weight Serum
Serum Serum
Day post infection
R.R.R. Rowland et al., Kansas State University Groups of ~200 commercial crossbred pigs infected with
PRRS virus isolate NVSL97-7985 between 18 and 28 d of age
Host Response Phenotypes
Body weight Log(viremia)
Rebound
Viral Load Area Under Curve
h2 = 0.41 h2 = 0.29
rp = -0.25 rg = -0.47
First Generation PHGC trials
Boddicker et al. J. Anim. Sci. 2012, Animal Genetics 2014, Genetics Selection Evolution 2014
Trial Parents Parental Breeds # piglets Sex
PHGC 1-3
Sires LW 562 All
Barrows Dams LR
PHGC 4 Sires Duroc
195 Barrows + gilts Dams LW/LR comp
PHGC 5 Sires Duroc
199 Barrows + gilts Dams LR/LW comp
PHGC 6 Sires LR
198 All Barrows Dams LR
PHGC 7 Sires Pietran
197 Barrows + gilts Dams LW/LR comp
PHGC 8 Sires Duroc
200 Barrows + gilts Dams Y/LR
Viral Load Weight Gain
Results of Genomic Analyses
Chr 4 Chr 4
1 Mb region explains 15%
of genetic variance
Includes important candidate
genes GBP1 GBP2 GBP5 GTF2B PKN2
11% of genetic
variance
95
100
105
110
115
120
1-8 1-3 4 5 6 7 8
Viru
s Lo
ad (a
rea
unde
r the
cur
ve)
Trial
AA AB BB
MAF = 0.17
a b b
a
b b
a
b
ab
a
b a
a
b
a b
ab
n=10
23
n=34
7 n=
44
n=37
6
n=15
n=
139
n=16
3 n=
28
n=4
n=12
4 n=
57
n=3
n=11
2 n=
11
n=87
n=
85
n=22
a a
n=15
8 n=
29
Boddicker et al. 2012, 2014a,b
WUR genotype
Effects of WUR10000125 on Viral Load Trials 1-8
8
10
12
14
16
18
20
22
24
All 1-3 4 5 6 7 8
Wei
ght G
ain
(kg)
Trial
AA AB BB
a
b b
a
b ab a
b ab
a
b
ab
a
b
a a
a
a
b
n=98
3 n=
345
n=43
n=36
2 n=
137
n=14
n=16
1 n=
28
n=4
n=12
2 n=
58
n=3
n=95
n=
11
n=87
n=
85
n=22
n=15
6 n=
26
Boddicker et al. 2012, 2014a,b
Effects of WUR10000125 on Weight Gain Trials 1-8
WUR genotype
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30 35 40
Vire
mia
(Log
10 T
empl
ates
/ml,
qPC
R)
Days Post Infection
AA
AB
P=3*10-7 1*10-9 1*10-16
9*10-12
2*10-6
7*10-4
0.07
Boddicker et al. 2012, 2014a,b
SSC 4 region effects over time PHGC1-8
5
10
15
20
25
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30 35 40
Wei
ght (
kg)
Vire
mia
(Log
10 T
empl
ates
/ml,
qPC
R)
Days Post Infection
AA
AB
P=3*10-7 1*10-9 1*10-16
9*10-12
2*10-6
7*10-4
0.07
0.01
3*10-7
2*10-8
6*10-9
Boddicker et al. 2012, 2014a,b
SSC 4 region effects over time PHGC1-8
Generation 1 & 2
PRRS trials
Trial Number n Breed PRRSv Isolate
1-3 530 LW x LR
NVSL
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
KS06 11 176 LW x LR 12 174 LR x LW 14 180 Duroc x LR/LW
Total 2304 challenged pigs with deep phenotypes
VIRAL LOAD WEIGHT GAIN
A major QTL for host response to PRRS on SSC 4
Boddicker et al. 2012, 2014a,b; Hess et al. 2015
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30 35 40
Log
10(V
irem
ia)
Days Post Infection
Viremia NVSL AA
Viremia NVSL AB
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30 35 40
Log
10(V
irem
ia)
Days Post Infection
Viremia KS06 AA
Viremia KS06 AB
Hess et al. 2015 rg(VL) = 0.86 (+0.19)
A major QTL for host response to PRRS on SSC 4
0
5
10
15
20
25
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30 35 40
Wei
ght (
kg)
Log
10(V
irem
ia)
Days Post Infection
Viremia NVSL AAViremia NVSL ABWeight NVSL AAWeight NVSL AB
0
5
10
15
20
25
0
1
2
3
4
5
6
7
0 5 10 15 20 25 30 35 40
Wei
ght (
kg)
Log
10(V
irem
ia)
Days Post Infection
Viremia KS06 AAViremia KS06 ABWeight KS06 AAWeight KS06 AB
Hess et al. 2015 rg(VL) = 0.86 (+0.19) rg(WG) = 0.86 (+0.27)
A major QTL for host response to PRRS on SSC 4
Genomic regions do not overlap between PRRSV isolates But pathways do
KS06
NVSL WUR = 21
WUR = 7 WUR = 7
WUR = 21
Waide et al.
Identification of other host response QTL
Viral Load
rg(NVSL, KS06) = 0.86 (+0.19)
KS06
NVSL WUR = 16 WUR = 16
Weight Gain
rg(NVSL, KS06) = 0.86 (+0.27)
Identification of other host response QTL
Estimate SNP
effects SNP Genotypes
Phenotypes
SNP Genotypes
Genomic Prediction
Meuwissen et al. 2001
Training population
Selection candidates
Genomic Prediction Prediction using high-density SNPs
Conclusions
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 + PCV2 (incl. PRRS vaccination)
4. Field trials
Iowa State University 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
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
Funding Industry Partners
Scientific Collaborators
NIFA
Thanks to all Partners