Dr. Jack Dekkers - Update on the host genetics of resistance to porcine diseases
Transcript of 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