dr. jack dekkers - update on the host genetics of resistance to porcine diseases

Update on the host genetics of resistance to porcine diseases

Wean-Finish

Jack Dekkers 

Department of Animal ScienceIowa State University

Evolution of PRRSHost Genetics Research

1. Experimental infection of nursery pigs with NVSL

2. Experimental infection of nursery pigs with KS06

3. Experimental co-infection of nursery pigs: PRRS + PCV2 (incl. PRRS vaccination)

4. Field trials

5. Natural Challenge Model

NIFA

NIFA

NIFA

Lunney, RowlandDekkers, Reecy

0 5 10 15 20 25 30 35 400

1

2

3

4

5

6

7

AA

AB

Days Post Infection

Vire

mia

(Log

10 T

empl

ates

/ml,

qPC

R)

P=3*10-71*10-9 1*10-16

9*10-12

2*10-6

7*10-4

0.07

Boddicker et al. 2012, 2014a,b

Effects of a Major Geneon SSC4 NVSLBoddicker et al. 2012, 2014a,b

Nursery pig model for PRRS

0 5 10 15 20 25 30 35 400

1

2

3

4

5

6

7

5

10

15

20

25

AAAB

Days Post Infection

Vire

mia

(Log

10 T

empl

ates

/ml,

qPC

R)

Wei

ght (

kg)

P=3*10-71*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

Effects of a Major Geneon SSC4 NVSLBoddicker et al. 2012, 2014a,b

Nursery pig model for PRRS

VIRAL LOAD WEIGHT GAIN

Effects of a Major Geneon SSC4 NVSL / KS06

Boddicker et al. 2012, 2014a,b

Laura Constance et al. Abstract # 37

2016. Cell Host & Microbe 19, 504–514

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

Vaccination & Co-infection Trials4 groups of 200 commercial crossbred piglets (18-21 d)

50 AA Vaccinated (PRRS MLV) 50 AB

50 AA Non-vaccinated 50 AB

GBP5 GBP5

Co-infection with PRRSv and PCV2 PCVAD

Translational GenomicsUSDA-NIFA grant # 2013-68004-20362NIFA

Effect of GBP5 on PCV2b viremiafollowing PRRS vaccination

Jenelle Dunkelberger et al.

0 4 7 11 14 21 28 35 420

0.51

1.52

2.53

3.54

4.55

Non-Vx AA

Day Post Infection

PCV2

b V

irem

ia

(log1

0 te

mpl

ates

/reac

tion)

0 4 7 11 14 21 28 35 420

1

2

3

4

5

6

Non-Vx AANon-Vx AB

Day Post Infection

PCV2

b V

irem

ia

(log1

0 te

mpl

ates

/reac

tion)

Effect of GBP5 on PCV2b viremiafollowing PRRS vaccination

Jenelle Dunkelberger et al.

GBP5 QTL does NOT affectoverall performance in clean environments

Jenelle Dunkelberger et al. (Abstract #44)

Line Selection Index P-value

DamA 0.74

B 0.15

SireC 0.48

D 0.69

• Marker assisted selection based on GBP5 genotype is a promising strategy to select for improved response…– Not just to PRRSV infection, also co-infection with PCV2b– And perhaps other pathogens?– No negative effect on performance without major disease

• For PCV2b VL, the effect of GBP5 was significant for Vx pigs, but not for Non-Vx pigs

• Numerically, the effect of GBP5 was greater upon primary vs. secondary PRRSV exposure

• Consistent with role of GBP5 in innate response

Conclusions

TranscriptomeAnalyses

NIFA

Ongoing Transcriptome analyses

Objectives

Identify differentially expressed genes and pathways related to host response to co-

infection with/out prior vaccination for PRRS

Determine the effect of tonsil PRRS viral level and PRRS isolate on tonsil gene expression

Qian (Jessie) Dong, Joan Lunney,Elyn Fritz-Waters, Yet Nguyen, Bob RowlandAndrew Hess, James Reecy, Jack Dekkers

Gene expression analyses7 x 4 litter mates from PHGC16

Vx

AA AB

Non-Vx

AAn=7

ABn=7 n=7n=7

GBP5A

rriv

eVa

cci-

nate

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

Serum 3’ RNAseq 192 samples

3’ RNA seq

The effect of PRRS viral level and isolate on tonsil gene expression

42 days after infectionAbstract # 43

Qian (Jessie) Dong1, Joan Lunney2,Elyn Fritz-Waters1, Yet Nguyen1, Bob Rowland3

Andrew Hess1, James Reecy1, Jack Dekkers1

1Iowa State University2USDA, ARS, BARC, APDL

4Kansas State University

Relationship between the serum viremia and tonsil viremia at 42 dpi

Seru

m V

iral L

oad

0-21

dpi

Se

rum

Vire

mia

42

dpi

Tonsil viremia 42 dpi Tonsil viremia 42 dpi

Tonsil virus class # pigs for RNA-seq

NVSLHigh 15Low 15

KS06High 12Low 10

# DEG between Isolateand Tonsil Viremia

Dong et al.Abstract # 43

B

APLA

PLB

B

A

GA

GB BA

PLA PLB

GA

GB

ResistanceAbility to prevent infection or limit

replication

Resistance, Tolerance, or Resilience?

ToleranceAbility to maintain performance as

pathogen load increases

Resilience Robustness

Ability to maintain performance upon

exposure to a pathogen

80 85 90 95 100 105 110 115 120 12513

14

15

16

17

18

19

20

21

22

23 NVSLAA

AB

Viral Load

42-d

Gro

wth

(kg)

WUR*slope p-value = 0.29

80 85 90 95 100 105 110 115 120 12513

14

15

16

17

18

19

20

21

22

23 KS06

Viral Load

42-d

Gro

wth

(kg)

WUR*slope p-value = 0.21

GBP5 QTL for PRRSResistance, Tolerance,

or Resilience?Hess et al. (unpublished)

AAAB AAAB

Application of Genomics to Improve Disease Resilience and Sustainability

in Pork ProductionMichael Dyck, John Harding, Bob Kemp

NIFA

3500 YXLR WEANER PIGS FROM HIGH-HEALTH

HERDSBATCHES OF 60-75 PIGS/3

WEEKS NATURAL CHALLENGE FACILITYQUARANTINE NURSERY

SEEDER PIGS

Continuous flow

Genetics of Resilience under Natural Challenge

Pathogens in Natural Challenge Farm (October 2016) (Harding)

3500 YXLR WEANER PIGS FROM HIGH-HEALTH

HERDSBATCHES OF 60-75 PIGS/3

WEEKS

PREDICTIVEPHENOTYPES collected on

young healthy pigsImmune Response• High Immune Response• In vitro immune tests• Phagocytosis tests

Blood Transcriptome

Blood Metabolome

Blood Proteome

RESILIENCE PHENOTYPEScollected on all pigs

Mortality/Morbidity

Growth performance

Feed intake

Water intake

Disease diagnostics

Gut Microbiome

Blood transcriptome

Gut Microbiome

NATURAL CHALLENGE FACILITYQUARANTINE NURSERY

SEEDER PIGS

Continuous flow

Genetics of Resilience under Natural Challenge

Austin Putz

Austin Putz

3500 YXLR WEANER PIGS FROM HIGH-HEALTH

HERDSBATCHES OF 60-75 PIGS/3

WEEKS

PREDICTIVEPHENOTYPES collected on

young healthy pigs

80 K SNP genotypes

Immune Response• High Immune Response• In vitro immune tests• Phagocytosis tests

Blood Transcriptome

Blood Metabolome

Blood Proteome

TARGET RESILIENCE PHENOTYPESRESILIENCE

collected on all 3500 pigs

Mortality/Morbidity

Growth performance

Feed intake

Water intake

Disease diagnostics

Trait Genetics• Parameters• Architecture• Mechanisms

GeneticPrediction

of Resilience

PhenotypicPrediction

of Resilience

PROJECTDELIVE-RABLES

Gut Microbiome

Integrated statistical

and bioinformatic

analyses

Blood transcriptome

Gut Microbiome

NATURAL CHALLENGE FACILITYQUARANTINE NURSERY

SEEDER PIGS

Continuous flow

Evolution of PRRS Host Genetics Research

1. Experimental infection of nursery pigs with NVSL

2. Experimental infection of nursery pigs with KS06

3. Experimental co-infection of nursery pigs: PRRS + PCV2 (incl. PRRS vaccination)

4. Field trials

5. Natural Challenge Model

NIFA

NIFA

NIFA

Iowa State UniversityNick Boddicker Andrew Hess

Emily Waide Chris EisleyJenelle Dunkelberger

James Koltes Eric Fritz-WatersMartine Schroyen Nick Serao

Jim Reecy Chris TuggleSusan Carpenter

Kansas State UniversityBob Rowland PRRS group

Ben Trible Megan NiederwerderMaureen Kerrigan Becky Eaves et al

USDA-ARSJoan Lunney group

Igseo Choi Sam AbramsUniversity of Alberta

Graham Plastow groupUniv. SaskatchewanJohn Harding group

Roslin InstituteSteve Bishop

Andrea Doeschl-WilsonZeenath Islam Graham Lough

Univ. MinnesotaMonserat Torremorrell

Funding Industry Partners

ScientificCollaborators

NIFA

Thanks to all Partners

Coming Spring 2017: Online course

Goal: Train veterinarians and geneticists on concepts of genetic selection & genomics and their application to improve animal health

What: On-line, asynchronous, videos made by experts, essential readings, self-paced

Unit 1: Introduction to disease

biology

Unit 2: Genetics

and genetic selection

Unit 3: Genetic

selection for disease

resistance

Unit 4: Genetic

selection for PRRS virus

Principles and Applications of Genetics and Genomics to Improve Animal Health

More information

Poster on display at this conference.

Coming Spring 2017: Online course