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

KS06 NVSL

Can we use Genomic Prediction across isolates?

NVSL Trials

KS06 Trials

19

r/h

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