1

Name:

Animal Genetics and Diseases

Wellcome Genome Campus Conference Centre, Hinxton, Cambridge, UK

8-10 May 2019

Scientific Programme Committee:

Leif Andersson

Uppsala University, Sweden

Mark Fife

The Pirbright Institute, UK

Susan Lamont

Iowa State University, USA

Helen Sang

The Roslin Institute, UK

Tweet about it: #AnimalGenetics2019

@ACSCevents /ACSCevents /c/WellcomeGenomeCampusCoursesandConferences

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Wellcome Genome Campus Scientific Conferences Team:

Rebecca Twells

Head of Advanced Courses and

Scientific Conferences

Treasa Creavin

Scientific Programme

Manager

Nicole Schatlowski

Scientific Programme

Officer

Jemma Beard

Conference and Events

Organiser

Lucy Criddle

Conference and Events

Organiser

Sarah Offord

Conference and Events

Office Administrator

Zoey Willard

Conference and Events

Organiser

Laura Wyatt

Conference and Events

Manager

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Dear colleague,

I would like to offer you a warm welcome to the Wellcome Genome Campus Advanced Courses and

Scientific Conferences: Animal Genetics and Diseases. I hope you will find the talks interesting and

stimulating, and find opportunities for networking throughout the schedule.

The Wellcome Genome Campus Advanced Courses and Scientific Conferences programme is run on a

not-for-profit basis, heavily subsidised by the Wellcome Trust.

We organise around 50 events a year on the latest biomedical science for research, diagnostics and

therapeutic applications for human and animal health, with world-renowned scientists and clinicians

involved as scientific programme committees, speakers and instructors.

We offer a range of conferences and laboratory-, IT- and discussion-based courses, which enable the

dissemination of knowledge and discussion in an intimate setting. We also organise invitation-only

retreats for high-level discussion on emerging science, technologies and strategic direction for select

groups and policy makers. If you have any suggestions for events, please contact me at the email address

below.

The Wellcome Genome Campus Scientific Conferences team are here to help this meeting run smoothly,

and at least one member will be at the registration desk between sessions, so please do come and ask

us if you have any queries. We also appreciate your feedback and look forward to your comments to

continually improve the programme.

Best wishes,

Dr Rebecca Twells Head of Advanced Courses and Scientific Conferences rebecca.twells@wellcomegenomecampus.org

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General Information

Conference Badges

Please wear your name badge at all times to promote networking and to assist staff in identifying you.

Scientific Session Protocol

Photography, audio or video recording of the scientific sessions, including poster session is not

permitted.

Social Media Policy

To encourage the open communication of science, we would like to support the use of social media at

this year’s conference. Please use the conference hashtag #AnimalGenetics2019. You will be

notified at the start of a talk if a speaker does not wish their talk to be open. For posters, please check

with the presenter to obtain permission.

Internet Access

Wifi access instructions:

Join the ‘ConferenceGuest’ network

Enter your name and email address to register

Click ‘continue’ – this will provide a few minutes of wifi access and send an email to the

registered email address

Open the registration email, follow the link ‘click here’ and confirm the address is valid

Enjoy seven days’ free internet access!

Repeat these steps on up to 5 devices to link them to your registered email address

Presentations

Please provide an electronic copy of your talk to a member of the AV team who will be based in the

meeting room.

Poster Sessions

Posters will be displayed throughout the conference. Please display your poster in the Conference

Centre on arrival. There will be two poster sessions during the conference as detailed below. The

page number of your abstract in the abstract book indicates your assigned poster board number. An

index of poster numbers appears in the back of this book.

Odd number poster assignments will be presenting in poster session 1, which takes place on

Wednesday, 8 May at 18:00 - 19:30.

Even number poster assignments will be presenting in poster session 2, which takes place on

Thursday, 9 May at 17:45 - 19:15.

Conference Meals and Social Events

Lunch and dinner will be served in the Hall, apart from the lunch on Wednesday, 8 May when it will be

served in the Conference Centre. Please refer to the conference programme in this book as times will

vary based on the daily scientific presentations. Please note there are no lunch or dinner facilities

available outside of the conference times.

All conference meals and social events are for registered delegates. Please inform the conference

organiser if you are unable to attend the dinners.

A cash bar will be open from 19:00 – 23:00 each day.

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Dietary Requirements

If you have advised us of any dietary requirements, you will find a coloured dot on your badge. Please

make yourself known to the catering team and they will assist you with your meal request.

If you have a gluten or nut allergy, we are unable to guarantee the non-presence of gluten or nuts in

dishes even if they are not used as a direct ingredient. This is due to gluten and nut ingredients being

used in the kitchen.

For Wellcome Genome Campus Conference Centre Guests

Check in

If you are staying on site at the Wellcome Genome Campus Conference Centre, you may check into

your room from 14:00. The Conference Centre reception is open 24 hours.

Breakfast

Your breakfast will be served in the Hall restaurant from 07:30 – 09:00

Telephone

If you are staying on-site and would like to use the telephone in your room, you will need to

contact the Reception desk (Ext. 5000) to have your phone line activated – they will require your

credit card number and expiry date to do so.

Departures

You must vacate your room by 10:00 on the day of your departure. Please ask at reception for

assistance with luggage storage in the Conference Centre.

Taxis

Please find a list of local taxi numbers on our website. The Conference Centre reception will also

be happy to book a taxi on your behalf.

Return Ground Transport

Complimentary return transport has been arranged for 12:30 on Friday, 10 May to Cambridge

station and city centre (Downing Street), and Stansted and Heathrow airports.

A sign-up sheet will be available at the conference registration desk from 15:40 on Wednesday, 8

May. Places are limited so you are advised to book early.

Please allow a 40-minute journey time to both Cambridge city and Stansted airport, and up to 3

hours to Heathrow airport.

Messages and Miscellaneous

Lockers are located outside the Conference Centre toilets and are free of charge.

All messages will be available for collection from the registration desk in the Conference Centre.

A number of toiletry and stationery items are available for purchase at the Conference Centre

reception. Cards for our self-service laundry are also available.

Certificate of Attendance

A certificate of attendance can be provided. Please request one from the conference organiser

based at the registration desk.

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Contact numbers

Wellcome Genome Campus Conference Centre – 01223 495000 (or Ext. 5000)

Wellcome Genome Campus Conference Organiser (Zoey) – 07747 024256

If you have any queries or comments, please do not hesitate to contact a member of staff who will

be pleased to help you.

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Conference Summary

Wednesday, 8 May 2019

12:00 – 13:00 Registration with buffet lunch

13:00 – 13:10 Welcome and introduction

13:10 – 14:10 Keynote lecture 1 Linda Saif, OARDC/The Ohio State University, USA

14:10 – 15:40 Session 1: Genetics of immune response

15:40 – 16:10 Afternoon tea

16:10 – 17:40 Session 2: New technologies to assess and improve disease resistance

17:40 – 18:00 Lightning talks for poster session 1

18:00 – 19:30 Drinks reception and poster session 1 (odd numbers)

19:30 Buffet dinner

Thursday, 9 May 2019

09:00 – 10:30 Session 3: Quantitative genetics applied to disease

10:30 – 11:00 Morning coffee

11:00 – 12:30 Session 4: Epidemiology

12:30 – 14:00 Lunch

14:00 – 15:30 Session 5: Host pathogen interactions: microbiome, mechanisms

and modelling

15:30 – 16:00 Afternoon tea

16:00 – 17:30 Session 6: Comparative and functional genomics

17:30 – 17:45 Lightning talks for poster session 2

17:45 – 19:15 Drinks reception and poster session 2 (even numbers)

19:15 Served conference dinner

Friday, 10 May 2019

09:00 – 10:30 Session 7: Pathogen genetics and genomics

10:30 – 11:00 Morning coffee

11:00 – 12:00 Keynote lecture 2 Julian Knight, University of Oxford, UK

12:00 – 12:10 Closing remarks

12:10 – 12:30 Take away lunch

12:30 Coaches depart to Cambridge City Centre and Train Station, and Heathrow

Airport via Stansted Airport

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Animal Genetics and Diseases

Wellcome Genome Campus Conference Centre,

Hinxton, Cambridge

8 – 10 May 2019

Lectures to be held in the Francis Crick Auditorium

Lunch and dinner to be held in the Hall Restaurant

Poster sessions to be held in the Conference Centre

Spoken presentations - If you are an invited speaker, or your abstract has been selected for a

spoken presentation, please give an electronic version of your talk to the AV technician.

Poster presentations – If your abstract has been selected for a poster, please display this in the

Conference Centre on arrival.

Conference programme

Wednesday, 8 May 2019

12:00 - 13:00 Registration with lunch

13:00 - 13:10 Welcome and introduction

Programme Committee: Susan Lamont, Iowa State University, USA

13:10 - 14:10 Keynote lecture 1

Chair: Mark Fife, The Pirbright Institute, UK

Probiotics and commensals modulate gut reactions and immunity to rotavirus

in a neonatal piglet model

Linda Saif

OARDC/The Ohio State University, USA

14:10 - 15:40 Session 1: Genetics of immune response

Chair: Susan Lamont, Iowa State University, USA

14:10 Probing mechanisms of porcine reproductive and respiratory

syndrome (PRRS) resistance

Joan Lunney

USDA-ARS-Beltsville, USA

14:40 Generalists versus specialists: a new view of how MHC molecules

respond to infectious pathogens

Jim Kaufman

University of Cambridge, UK

15:10 Genetic control of specific and natural antibody production in

Canadian Holsteins

Bonnie Mallard

University of Guelph, Canada

9

15:25 Investigation of a (putative) causal mutation in Toll-like receptor family

member 1A in chickens

Tom Berghof

Wageningen University and Research, The Netherlands

15:40 - 16:10 Afternoon tea

16:10 - 17:40 Session 2: New technologies to assess and improve disease

resistance

Chair: Helen Sang, The Roslin Institute, UK

16:10 Genome editing for disease resistance in livestock

Christine Tait-Burkhard

The Roslin Institute, University of Edinburgh, UK

16:40 Breeding for improved health in layer chickens – challenges and

opportunities

Anna Wolc

Iowa State University, USA

17:10 Genome wide CRISPR knockout screen identifies host factors involved

in Bovine Herpes Virus Type 1 infection

Spring Tan

University of Edinburgh, UK

17:25 Estimating genetic and treatment effects for host susceptibility,

infectivity and recoverability using temporal epidemic data

Christopher Pooley

The Roslin Institute, University of Edinburgh, UK

17:40 - 18:00 Lightning talks for poster session 1

Chair: Mark Fife, The Pirbright Institute, UK

18:00 - 19:30 Poster session 1 (odd numbers) with drinks reception

19:30 Buffet Dinner

Thursday, 9 May 2019

09:00 - 10:30 Session 3: Quantitative genetics applied to disease

Chair: Leif Andersson, Uppsala University, Sweden

09:00 New genetic and genomic models for mastitis in dairy cattle

Dirk Jan de Koning

Swedish University of Agricultural Sciences, Sweden

09.30 Breeding for disease resistance in aquaculture species

Anna Sonesson

Nofima, Norway

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10:00 Quantitative analysis of the blood transcriptome of young healthy pigs

to improve disease resilience

Kyu-Sang Lim

Iowa State University, USA

10:15 Metabolome analysis of host response to NDV infection under heat

stress in two genetically distinct chicken inbred lines

Ying Wang

University of California, Davis, USA

10:30 - 11.00 Morning coffee

11:00 - 12:30 Session 4: Epidemiology

Chair: Alison Mather, Quadram Institute Bioscience, UK

11:00 Causes and consequences of dog ownership: a register-based

approach

Tove Fall

Uppsala University, Sweden

11:30 Quantitative genetics of infectious diseases: integrating Indirect

Genetic Effect models with diseases transmission models

Piter Bijma

Wageningen University, The Netherlands

12:00 Gene co-expression in the chicken thymus reveals unique responses

to lipopolysaccharide and acute heat stress

Melissa Monson

Iowa State University, USA

12:15 How to predict that some animals respond better to vaccination than

others: application to vaccination against Mycoplasma hyopneumoniae

in pigs

Fany Blanc

INRA, France

12:30 - 14:00 Lunch

14.00 - 15:30 Session 5: Host pathogen interactions: microbiome, mechanisms

and modelling

Chair: Mark Fife, The Pirbright Institute, UK

14:00 Novel insights on Salmonella colonization and persistence in poultry

intestinal tract

Huaijun Zhou

University of California, USA

14:30 Resistance and resilience of livestock to arbovirus infections

Massimo Palmarini

University of Glasgow, UK

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15:00 A CCR5 promoter variant increases susceptibility to arthritis

encephalitis virus in goats

Pier Luigi Acutis

Istituto Zooprofilattico Piemonte, Italy

15:15 Chicken STAU2 protein interacts with NS1 and is required for the

replication of H5N1 influenza avian virus

Guiping Zhao

Chinese Academy of Agricultural Sciences, China

15:30 - 16:00 Afternoon tea

16:00 - 17:30 Session 6: Comparative and functional genomics

Chair: Anna Sonesson, Nofima, Norway

16:00 Listening to your inner goddess: a spontaneous SCID pig as an

emerging model for cancer and regenerative medicine research

Christopher Tuggle

Iowa State University, USA

16:30 Molecular innovation and conservation across mammalian organ

development

Margarida Cardoso Moreira

University of Heidelberg, Germany

17:00 Different transcriptional response of susceptible and resistant fish

hints at the mechanism of KHV disease resistance in carp

Lior David

Hebrew University of Jerusalem, Israel

17:15 The discovery of chicken TNF-a proves that “missing genes” not

necessarily must remain missing

Nina Burkhardt

LMU Munich, Germany

17:30 - 17:45 Lightning talks for poster session 2

Chair: Helen Sang, The Roslin Institute, UK

17:45 - 19:15 Poster session 2 (even numbers) with drinks reception

19:15 Served conference dinner

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Friday, 10 May 2019

09:00 - 10:30 Session 7: Pathogen genetics and genomics

Chair: Christopher Tuggle, Iowa State University, USA

09:00 Whole genome sequencing to untangle transmission and antimicrobial

resistance of zoonotic pathogens

Alison Mather

Quadram Institute Bioscience, UK

09:30 The changing genome of Influenza A Viruses

Holly Shelton

The Pirbright Institute, UK

10:00 Directed Genome Evolution to identify bacterial genes for phagocyte

survival in a BCO hypervirulent isolate

Douglas Rhoads

University of Arkansas, USA

10.15 Exploring the impact of oxytetracycline on gut microbiome

homeostasis in rainbow trout (Oncorhynchus mykiss, W. 1792)

Christopher Payne

University of Stirling, UK

10:30 - 11:00 Morning coffee

11:00 - 12:00 Keynote lecture 2

Chair: Leif Andersson, Uppsala University, Sweden

Insights from understanding genetic drivers of the variable immune

response into human disease

Julian Knight

University of Oxford, UK

12.00 - 12:10 Closing remarks

Programme Committee: Helen Sang, The Roslin Institute, UK

12.10 - 12:30 Take away lunch

12:30 Coaches depart to Cambridge City Centre and Train Station, and

Heathrow Airport via Stansted Airport

13

These abstracts should not be cited in bibliographies. Materials contained herein should be

treated as personal communication and should be cited as such only with consent of the

author.

14

Notes

S1

Spoken Presentations Probiotics and commensals modulate gut reactions and immunity to rotavirus in a neonatal piglet model L. J. Saif, A. Miyazakia,, S. Kandasamy, F. Paim, D. Fischer, L. Deblais, A. Kumar, G. Rajashekara and A. N. Vlasova Food Animal Health Research Program, CFAES, Ohio Agricultural Research and Development Center, Dept of Vet Prev Med, The Ohio State University, USA; aNIAH, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan Rotavirus (RV) is a major enteric pathogen of infants and neonatal animals. Attenuated oral RV vaccines for animals often fail in the field, or vaccines lack efficacy in infants in impoverished regions. Knowledge of the ecology/pathogenesis of enteric viruses, the impact of preexisting factors (malnutrition, micronutrient/immune deficiencies, maternal antibodies, gut microbiota, etc) on vaccine effectiveness and mechanisms for stimulation of gut immunity in neonates are critical to design more effective RV vaccines for animals, and for infants in developing countries. Germ-free (GF) pigs are the only animal model susceptible to human rotavirus (HRV) diarrhea and their gut physiology, metabolism and mucosal immunity resemble that of human infants. The absence of microbiota allows us to reconstitute GF piglets with defined microbes, probiotics, etc to assess their impact on RV vaccines and gut immunity. Probiotics promote immune maturation and mediate beneficial health effects, but the mechanisms are largely undefined. We elucidated how Gram+ (lactobacillus or bifidobacteria), Gram- (Escherichia coli), or both probiotics influence neonatal intestinal homeostasis and immune maturation, moderate RV diarrhea and enhance oral RV vaccine effectiveness. Probiotic-colonized, RV vaccinated piglets had reduced RV shedding or diarrhea post-challenge with virulent RV (virRV) and enhanced gut IgA antibody responses to RV. Overall, dual colonization with selected Gram+ probiotics was more effective at promoting these effects than single Gram+ probiotics. The Gram- E. coli alone was more effective than the Gram+ probiotics alone or combined. Thus probiotics, alone or combined, exerted divergent immune modulating effects when interacting with attenuated RV oral vaccine (immunostimulatory- enhanced T and B cell responses) versus enteropathogenic RV (immunoregulatory - enhanced Tregs and anti-inflammatory cytokines). Malnutrition is prevalent in children in developing countries, where RV vaccines fail. We transplanted human infant fecal microbiota into GF piglets (HIFM pigs) to establish a clinically relevant model to assess the impact of protein malnutrition on RV infection and vaccine efficacy. We elucidated the innate, T cell and cytokine immune responses to attenuated RV (AttRV) vaccine and VirRV challenge in GF pigs or HIFM transplanted gnotobiotic (Gn) pigs fed protein-deficient or -sufficient bovine milk diets. Post- VirRV challenge, the protein-deficient vaccinated pigs had lower protection rates against diarrhea and significantly increased virus shedding titers (HIFM transplanted, but not GF pigs). Collectively, our findings revealed that protein malnutrition exacerbated RV infection and reduced vaccine efficacy, coinciding with significantly altered immune function (innate, T cell and cytokines), gut microbiota (decreased Firmicutes-to-Bacteroides ratios; increased Proteobacteria), intestinal crypt dynamics and metabolic and biochemical parameters. The exacerbated effects in HIFM transplanted vs GF pigs suggests that gut microbiota may compete with the host for limited dietary resources in protein malnourishment. Our novel insights into the immunological impairment and reduced efficacy of a RV vaccine in a protein deficient, HIFM pig model should aid in development of innovative strategies to overcome the reduced effectiveness of oral vaccines in malnourished children.

S2

Notes

S3

Probing mechanisms of porcine reproductive and respiratory syndrome (PRRS)

resistance

Joan K. Lunney

USDA-ARS, BARC, APDL, USA

Our team has probed the role of host genetics in determining resistance/susceptibility to

porcine reproductive and respiratory syndrome virus (PRRSV) infection in neonatal pig and

pregnant gilt models. Based on deep phenotyping and genomics the PRRS Host Genetics

Consortium (PHGC) team identified a major gene, GBP5 on SSC4, as the putative causative

mutation associated with decreased viral load and improved weight gain for neonatal PRRS.

A genetic marker (WUR) near GBP5 is now being used by industry for selection of PRRS

resistant pigs. Our recent PHGC analyses have focused on other resistance genes and

pathways associated with persistence of PRRSV in tonsil. Tonsil virus level was lowly

heritable and phenotypically associated: pigs with low tonsil virus levels had an earlier and

faster rate of maximal serum viral clearance. The tonsil transcriptome, at 42 days post

infection (dpi), was analyzed using both RNA-seq and a 230 gene NanoString array

(designed on biomarkers previously predicted to alter PRRS resistance/susceptibility).

Transcriptome studies, comparing PRRSV isolates and tonsil viral levels, support the

importance of immune cell influx in clearing persistent virus. The WUR gene and tonsil viral

load exhibited large effects on pathways involved in cell movement and tissue invasion, and

chemotaxis of phagocytes.

For reproductive PRRS University of Saskatchewan scientists have established a pregnant

gilt model to determine whether fetal mortality is the result of viral disruption of placental

function or poor fetal immune response to infection. At 21 dpi (107 days gestation) fetal

thymus transcriptome studies indicated that disease progression was associated with up-

regulation of genes associated with inflammation, innate immunity, and cell death signaling.

Maternal transcriptomic responses were associated with PRRS resilience including higher

basal gene expression correlated with platelet function, interferon (IFN) and pro-

inflammatory responses. Numerous genomic regions were associated with fetal viral load,

fetal death and viability, thus suggesting that selection for reproductive PRRS resilience may

be possible. To better understand transplacental fetal responses a time course experiment

was performed (2 – 14 dpi) and transcriptomic responses evaluated in fetal and placental

tissues. Gene expression, evaluated using NanoString arrays, revealed 35 genes that were

differentially regulated in both thymus and placenta, with a clear transcriptomic response to

type 1 IFNs including upregulation of STAT1-3 and IFN response genes. Efforts are

continuing to assess the impact of viral load in placenta and thymuses to distinguish the

effect of viral infection and cross placental transmission on fetal survival and local immune

responses.

S4

Notes

S5

Generalists versus specialists: a new view of how MHC molecules respond to infectious pathogens

Jim Kaufman

University of Cambridge, Department of Pathology/Department of Veterinary Medicine, UK

The highly polymorphic class I and class II molecules encoded by the major

histocompatibility complex (MHC) play central roles in adaptive and innate immune

responses, by presenting antigenic peptides to T lymphocytes as well as class I molecules

being recognized by natural killer (NK) cells. We would like to understand why and how the

chicken MHC, unlike the human MHC, determines very strong resistance or susceptibility to

certain infectious diseases.

We have found that only single MHC class I (and class II) genes are widely and strongly

expressed in chickens. From peptide motifs and crystallographic structures for many chicken

class I (and class II) molecules, we discovered that some alleles of the dominantly-

expressed (BF2) class I locus bind an astonishing variety of peptides but have relatively low

cell surface expression, while others have higher expression but very stringent requirements

for peptide binding leading to narrow peptide repertoires. Examining the literature, we find

that it is the relatively poorly-expressed promiscuous alleles that confer resistance to a wide

range of poultry pathogens.

A similar hierarchy of human class I alleles is evident from the literature, but it is some well-

expressed fastidious alleles that confer slow progression from human immunodeficiency

virus (HIV) infection to acquired immunodeficiency syndrome (AIDS), apparently due to

those particular MHC molecules binding peptides that the virus finds difficult to change

without a loss of fitness. These observations have led to the proposal of a hierarchy of

relatively poorly-expressed promiscuous generalist alleles to relatively well-expressed

fastidious specialist alleles, with many ramifications that we are currently trying to assess.

One interesting question is how generalists and specialists might evolve in populations of

chickens. We developed a polymerase chain reaction-next generation sequencing (PCR-

NGS) method that types the exons encoding the peptide-binding regions of all class I and

class II genes for up to 1200 chickens at a time, starting with a few blood cells. With many

collaborators who have contributed samples from around the world, we are using the typing

system to understand the population genetics of MHC genes and haplotypes, and to

underpin structural and functional studies that might be translated into breeding for disease

resistance and vaccine response, design of new vaccines, and so forth.

We have found that, globally, there is a huge diversity of chicken MHC alleles, many of

which are not found in the experimental chicken lines that have been the basis for research

over decades. Despite the fact that there are many tens of billions of commercial chickens,

they have extremely low MHC diversity, which might have been concerning from the

perspective of food security and public health. However, these commercial flocks are

strongly enriched in MHC haplotypes with low-expressing class I alleles, many of which are

known to be promiscuous peptide-binding and to confer resistance to a variety of common

infectious diseases.

S6

Notes

S7

Genetic control of specific and natural antibody production in Canadian Holsteins

Bonnie Mallard, Mehdi Emam, Britt de Klerk, Kathleen Thompson-Crispi

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Canada

Center for Genetic Improvement of Livestock, Dep. of Animal Biosciences, University of

Guelph, Canada

Antibodies (Abs) are effector molecules of immunity produced from B lymphocytes. Ab-

dependent-cytotoxicity, complement activation, and agglutination require Ab. To produce

specific Ab (Sp-Ab), B cells generally requires three signals: foreign antigen stimulation, co-

stimulatory molecule engagement and cytokine production. Following activation these B

cells, termed B-2 cells, proliferation, affinity maturation and isotype switch occurs. These

exquisitely specific B-2 cells exhibit all the hallmarks of the adaptive immune system -

diversity, specificity, memory. Conversely, natural Ab (NAb) from B-1 cells is present before

exposure to any foreign antigen and functions largely as part of the innate immune system.

Nabs are poly-reactive binding to phospholipids, glycolipids and glycoproteins offering early

protection following infections. In the current study genetic regions associated with NAb and

Sp-Ab production of Holsteins were compared. Concentrations of IgG Sp-Ab against a type

II protein antigen in sera from 4,478 samples, as well as serum IgG and IgM NAb to a

glycoprotein KLH, in 925 cows were quantified by ELISA. Samples were genotyped by

Illumina 50K and Zoetis ZM2 chips, and imputed to a common panel of 45,187 SNPs.

Associations were tested using numerical regression followed by adjusting for multiple

comparison error using FDR 0.05. Results showed genomic heritabilities of 0.37 (IgG Sp-

Ab), 0.27 (IgG NAb) and 0.31 (IgM NAb). Significant SNPs on chromosomes 2, 11, 14, 21

and 23 were found with Sp-Ab. Alternatively, significant SNPs on chromosomes 1, 20 and 21

were found with IgG NAb. None of the SNPs were significantly associated with IgM NAb.

Functional annotation analysis showed genes with roles in antigen processing/presentation,

and cell trafficking over-represented for Sp-Ab. Exocytosis is a process necessary to release

both types of Ab, but it was only observed in association with NAb. Absence of these SNPs

with Sp-Ab might be due to the larger effect of antigen processing and presentation in

producing Sp-Ab. It should be noted that genes with roles in immunoglobulin class-switching,

TRAF3 and XRCC3, were found adjacent to the SNPs associated with IgG NAb. This likely

reflects the role of hypermutation and class-switching in production of IgG NAb which is

likely following antigenic stimulation from self or microbiome in producing IgG NAb, but not

IgM NAb. The lack of SNPs to NAb may be indicative of its more broadly polygenic nature

with no major gene effects. Together these findings suggest, as in other species, bovine Sp-

and NAb are generated independently from different B-cell lineages.

S8

Notes

S9

Investigation of a (putative) causal mutation in Toll-like receptor family member 1A in

chickens

Tom V.L. Berghof1*, Carlos G.P. Voogdt2*, Joop A.J. Arts3, Henk Bovenhuis1, Henk K.

Parmentier3, Jan J. van der Poel1, Jos P.M. van Putten2, Marleen H.P.W. Visker1

1 Wageningen University & Research Animal Breeding & Genomics, The Netherlands

2 Department of Infectious Diseases & Immunology, Utrecht University, The Netherlands

3 Wageningen University & Research Adaptation Physiology, The Netherlands

* Equal contribution

Toll-like receptors (TLR) are transmembrane proteins recognizing pathogen-associated

molecular patterns with common molecular characteristics conserved in multiple microbial

species. Thus, TLR recognize a wide range of different pathogens, and thereby play a

central role in maintaining health. Not surprisingly, genetic variation in TLR has been

associated with diseases. Recent genome-wide association studies on, amongst other,

keyhole limpet hemocyanin-binding IgM natural antibodies (NAb) in chickens revealed a

putative causal mutation (Phe126Leu) in TLR family member 1A (TLR1A). The putative

causal mutation explained 63.5% of the genetic variation and showed full dominance

(Berghof et al., 2018, Front Immunol). In this study, the putative TLR1A causal mutation was

further investigated at the functional level to 1. confirm causality, and 2. investigate

associated effects on the humoral immune system. To confirm causality, differences in

receptor activation were assessed. Chicken TLR1A forms a heterodimer with TLR2B and

recognizes bacterial lipoproteins, mycoplasma, and related (synthetic) structures (e.g.

Pam3CSK4). HeLa cells carrying a luciferase reporter driven by the pro-inflammatory

transcription factor NF-kB were transfected with chicken TLR2B and either one of the allele

variants of the identified TLR1A mutation, and stimulated with Pam3CSK4. While cells

expressing the TLR1A-Phe126 variant were activated in a dose-dependent fashion, the

TLR1A-Leu126 variant failed to respond to ligand stimulation. This suggests that the

Leu126-mutation resulted in a loss-of-function of the TLR1A protein, and thus represents a

'natural knock-out'. Associated effects on the humoral immune system are currently

investigated. We are studying the effects of the two TLR1A allele variants on NAb during life

of chickens, as well as possible differences in maternal genetic effects of TLR1A on NAb in

offspring. Finally, we will investigate differences between the two TLR1A allele variants on

avian pathogenic Escherichia coli infection at a young age. The presented results will give

more insight in the role of genetic variation in TLR, and their role in humoral immunity.

Ultimately, this will result in more knowledge on breeding for disease resistance in a non-

specific fashion.

S10

Notes

S11

Genome editing for disease resistance in livestock

Christine Tait-Burkard

Department of Infection & Immunity/Department of Genetics & Genomics, University of

Edinburgh, The Roslin Institute, UK

With the world population predicted to reach almost 10 billion by 2050 there are a number of

challenges in sustainable management of finite resources. The rising demand for food

requires improved productivity of agricultural systems. One of the major burdens on the

livestock industry is loss of animals and decrease of production efficiency due to disease.

Furthermore, it is important to improve the health and welfare of animals by reducing and

preferably preventing the effects of disease. Advances in sequencing technology and

genome editing techniques provide the unique opportunity to generate animals with

improved traits. Recent examples of genome editing for disease resistance in pigs show that

this technology can be successfully applied in generating disease resistant animals. They

also highlight the potential risks, technological advances, as well as the political and societal

changes that will be required to successfully integrate genome editing technology into

livestock breeding.

S12

Notes

S13

Breeding for improved health in layer chickens – challenges and opportunities

Anna Wolc1,2, Wioleta Drobik-Czwarno1,3, Susan J. Lamont1

1Department of Animal Science, Iowa State University, Ames, Iowa, USA; 2Hy-Line Int.,

Dallas Center, Iowa, USA; 3Department of Animal Genetics and Breeding, Warsaw

University of Life Sciences, Warsaw, Poland

Health status is one of the major factors determining welfare and productivity of layer

chickens. Several management strategies are available to limit the probability of disease

outbreaks with major roles of biosecurity and vaccinations. A complementary approach

providing sustainable and cumulative results is the use of selection for improved disease

resistance and robustness.

Effectiveness of selection for improved health is conditional on the presence of genetic

variability in host response to challenges, which across multiple studies using biotic and

abiotic stressors is usually around 10% of phenotypic variability. Besides relatively low

heritability, selection for disease resistance is challenging because it requires accurate

recording of phenotypes every generation, which is often difficult in field conditions or

expensive under controlled challenge conditions. Despite these challenges, long term

selection for resistance to specific pathogens was shown to be successful in chickens.

Development of “omics” tools improves understanding of the genetics of host-pathogen

interactions, enables identification of genomic regions associated with disease resistance

(GWAS), identifies genes that respond to environmental challenges (transcriptomics) and

increases accuracy of selection (genomic selection). In the case of a simple mode of

inheritance, resistance alleles could be bred to fixation by selection provided sufficient

frequency and potentially be introduced to other populations by gene editing. However,

resistance to the majority of studied diseases in chicken is determined by many genes with

small effects (polygenic inheritance) and thus genomic selection is the current method of

choice for genetic improvement of health in poultry.

Application of the traditional and “omics” tools to research on heat stress mortality, host

response to Marek’s Disease, Newcastle Disease and Avian Influenza will be used to

illustrate challenges and opportunities in breeding for improved health in chickens.

S14

Notes

S15

Genome wide CRISPR knockout screen identifies host factors involved in Bovine

Herpes Virus Type 1 infection

Wenfang Spring Tan, Inga Dry, Simon Lillico, Andy Law, Bruce Whitelaw, Bob Dalziel

a. Division of Infection and Immunity; b. Division of Developmental Biology; c. Division of

Genetics and Genomics, the Roslin Institute, University of Edinburgh, UK

CRISPR/Cas9 are molecular scissors that cut DNA in a site-specific manner; it relies on

base pairing between the small CRISPR guide RNA (gRNA) and target DNA. This activity

guides the gRNA-bound Cas9 protein to the target and exert cutting, creating double strand

breaks in the DNA that are repaired by the cell, often resulting in gene inactivating indels.

Since the specificity of CRISPR/Cas9 is primarily determined by the base pairing, it is

straightforward to introduce many guides with altered gRNA sequences to achieve knockout

of many genes in parallel. To enable whole genome screening in cattle, we utilized this high

throughput strategy and produced a CRISPR library with a pool of 96,000 guides targeting

coding sequences of 21,212 genes in the cow genome. We observed good performance

after transducing this library, one guide per cell, into our MBDK cell line that stably

expresses Cas9 from the rosa26 locus: guides targeting core essential genes are

significantly depleted while those targeting non-essential genes or non-cutting control guides

remain largely unchanged.

Bovine Herpes Virus Type 1(BHV-1) causes infectious bovine rhinotracheitis, fatalities in

calves and pregnancy abortions in cows, leading to huge economy loss to cattle farmers in

Ireland and the UK. Unfortunately, little is known about how host cell factors intervene or

facilitate BHV-1 infection, and this lack of knowledge impedes vaccine and drug

developments. Thus, to study interactions between BHV-1 and the host, we infected the

library transduced cells with a GFP tagged BHV-1 at high MOI, and FACS sorted live cells at

10 hours post infection into sub-populations with different intensities of GFP signals. We

identified lists of genes with significantly depleted or enriched guides from these sub-

populations, from the GFP negative cells in particular. In GFP negative cells, genes targeted

by enriched guides are candidates that facilitate or are essential for BHV-1 infection whereas

genes targeted by depleted guides may inhibit this virus. We are currently validating some of

these gene candidates using drug inhibitors and individual gRNAs that knockout, activate or

repress gene expressions.

S16

Notes

S17

Estimating genetic and treatment effects for host susceptibility, infectivity and recoverability using temporal epidemic data

Christopher Pooley, Glenn Marion and Andrea Doeschl-Wilson

The Roslin Institute, University of Edinburgh, UK

In the era of rapid expansion of the human population with increasing demands on food

security, effective solutions that reduce the incidence and impact of infectious diseases in

plants and livestock are urgently needed. Even within a species hosts differ widely in their

response to infection and therefore also in their relative contribution to the spread of infection

within and across populations. Three key epidemiological host traits affect infectious disease

spread: susceptibility (propensity to acquire infection), infectivity (propensity to pass on

infection to others) and recoverability (propensity to recover quickly). Disease control

strategies aimed at reducing disease spread may, in principle, target improvement in any

one of these three traits. In this talk we introduce a novel software tool called SIRE (standing

for "susceptibility, infectivity and recoverability estimation"), which allows, for the first time,

simultaneous estimation of single nucleotide polymorphism (SNP) and treatment effects on

these host traits (so identifying potential pleiotropic effects). SIRE implements a Bayesian

algorithm which makes use of temporal data (consisting of any combination of recorded

infection times, recovery times or disease status measurements) from multiple epidemics

whose dynamics can be represented by the susceptible-infectious-recovered (SIR) model.

Validation of SIRE was achieved through simulation studies (that demonstrate unbiased

posterior parameter estimates), which were also used to evaluate parameter precision under

different data scenarios. This analysis revealed that, generally speaking, genetic effects

associated with recoverability can be estimated with highest precision, followed by

susceptibility and finally infectivity. In the latter case it was found that many epidemics with

few individuals give substantially more statistical power than the reverse. In an idealised

scenario in which infection and recovery times of individuals are precisely known, these

results are backed up by analytically derived expressions. However even when data is

incomplete data, good estimates of genetic effects are found to still be possible, albeit

requiring more individuals (e.g. when only recovery times are known around four times as

many individuals are needed to give equivalent precision to the idealised case). SIRE

represents an exciting new tool for analysing a wide range of experimental and field disease

data with the aim of discovering new genes underlying disease transmission.

S18

Notes

S19

New genetic and genomic models for mastitis in dairy cattle

Berihu Welderufael1,2, Peter Løvendahl, Luc Janss2, Freddy Fikse1,3 and Dirk Jan de Koning1

1Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences,

Uppsala, Sweden 2Center for Quantitative Genetics and Genomics, Department of Molecular Biology and

Genetics, Aarhus University, Tjele, Denmark 3Växa Sverige, Uppsala, Sweden

Mastitis is easily the most prevalent and most costly infectious disease in dairy cattle.

Because mastitis is very frequent and unavoidable, adding recovery information into the

genetic evaluation of mastitis is of great interest from an economical and animal welfare

point of view. Historically, genetic analyses of mastitis have only considered the

susceptibility to mastitis, leaving aside the other aspect of the disease - the recovery

process. Here we studied susceptibility to- and recovery from mastitis in joint genetic

analyses. The joint analyses allow us to estimate a correlation between genetic effects

influencing susceptibility and recovery. Subsequently, we have performed genome-wide

association studies (GWAS) to identify associated single nucleotide polymorphisms (SNPs)

and investigate the genetic background not only for susceptibility to - but also for

recoverability from mastitis. Somatic cell count records from 993 Danish Holstein cows

genotyped for 39,378 autosomal SNP markers were used for the association analysis.

Single SNP regression analysis was performed using the statistical software package DMU.

The heritabilities for ‘susceptibility’ and ‘recovery’ were both around 0.08. The genetic

correlation between susceptibility and recovery from mastitis was -0.83. A number of

significant SNP variants were identified for both traits. Many of the SNP variants associated

either with susceptibility to - or recoverability from mastitis were located in or very near to

genes that have been described for their role in the immune system. In contrast to the

overall genetic correlation, the significant SNP effects affected only one of the traits. This

could be due to the low power of the GWAS. Although susceptibility and recovery from

mastitis are strongly correlated, recovery could be considered as a new trait for selection.

Given the lack of major gene effects, whole genome selection may be the best way forward

to reduce mastitis in the population.

S20

Notes

S21

Breeding for disease resistance in aquaculture species

Anna K. Sonesson

Nofima AS, Norway

Already in the 1990s, tests were set up to challenge Atlantic salmon for resistance to

diseases. Sibs of selection candidates were tested and between family breeding values were

estimated, because of biosecurity reasons. Over time, the number of diseases that are

included in the breeding goals have increased. Overall, heritability of resistance to virus are

medium to high, and genetic correlations to production efficiency traits are low. The same

pattern is often seen in other aquaculture species. It may be explained by the short selection

history of aquaculture species, which may also explain why large QTL for virus diseases are

found in fish.

With genomic selection, the same design of the breeding programme is used. Groups of sibs

are used as a reference population that gets phenotypic and genomic information. Genomic

selection programmes typically result in increased accuracy of selection of 15-30%. Small

numbers of SNPs (hundreds instead of thousands) selected on their results in

transcriptomic, GWAS or eQTL studies can explain a large part of the genetic variation

(>40%), but still the accuracy of genomic selection is lower than for full genome-wide

genomic selection schemes. Genotyping costs are high for genomic selection in populations

with 100-600 families of 30-100 selection candidates and 10-50 sibs of selection candidates

that are tested per family per trait, and cost-reducing methods are sought. Genomic

selection can be applied within-families in breeding programmes with large families. Then,

pedigree information is used to calculate the between-family component and the genomic

data is used to calculate the within-family component only. A lower number of markers

(hundreds instead of tens of thousands) is then needed. Using DNA pooling of fish with

dead/alive phenotypes as a reference population is another cost-reducing genomic selection

method.

Recording of disease resistance is difficult in aquaculture populations, because individual

identification occurs rather late in life. Identification-by-genotyping can alleviate this problem

for e.g. test individuals. Most registrations of individual fish require handling of the fish, which

is costly and imposes stress to the fish that can influence the recorded trait. Challenge tests

are also only partly mimicking the natural resistance to the disease, and results may differ

depending on how the infection is introduced. Finally, the definition of the traits affects the

results, e.g. resistance, tolerance and infectivity, dead/alive or days to death, number of

parasites at which development stage. Electronic methods might provide new opportunities

for the recording of these difficult traits.

S22

Notes

S23

Quantitative analysis of the blood transcriptome of young healthy pigs to improve disease resilience

Kyu-Sang Lim1, Austin Putz1,5, Qian Dong1, Chris Tuggle1, Michael Dyck2, PigGen Canada, Frederic Fortin3, John Harding4, Graham Plastow2, and Jack Dekkers1

1Iowa State University, USA, 2University of Alberta, 3Centre de Developpement du Porc du Quebec inc., 4University of Saskatchewan, and 5Hypor inc.

Blood is a meaningful sample for reflecting the current health status of pigs. Here, we

investigated gene expression profiles in the blood of healthy piglets collected after weaning

for their association to measures of resilience after exposure to a natural polymicrobial

disease challenge at ~41 days of age until market weight. Weaned barrows (n = 435,

Yorkshire x Landrace, in 7 batches) from healthy multiplier farms were moved to the

experimental facility in Québec, Canada. Blood samples were collected at ~27 days of age

while the pigs were acclimating in a biosecure quarantine nursery and then moved to the

challenge nursery and then finisher. Four resilience traits were evaluated during the natural

disease challenge: mortality, average daily gain in the challenge nursery and finisher, and

the number of health treatments standardized to 180 days. Gene expression profiling of

blood samples was by 3'mRNA sequencing and a flow cytometry-based hematology

analyzer was used to quantify white blood cell (WBC) differentials. Normalized and log2

transformed counts for a total of 16,799 genes were analyzed with mixed linear models with

(WI) or without (WO) accounting for WBC composition. Comparing these two models, more

than half of the genes (n = 9,385) showed lower Akaike information criterion values for the

WI model (FDR < 0.10), indicating their observed level of expression was affected by WBC

composition. In the analysis of associations of the blood gene expression profiles with

subsequent resilience traits, residuals of the single gene expression values of the WO or WI

models and eigenvalues of gene modules from weighted gene co-expression network

analysis were fitted as covariates, one-by-one, in a mixed linear model for analysis of each

resilience trait. Most of the significant associations of gene expression with resilience were

for mortality (FDR < 0.20). The expression residuals of 2,040 genes from the WO model

were significantly associated with mortality. Among these, 1,308 genes were also significant

based on expression residuals from the WI model. The latter were enriched for terms related

to post-transcriptional regulation and translation. Also, 7 gene modules based on WO

residuals and 7 gene modules based on WI residuals were significantly associated with

mortality (FDR < 0.05). In conclusion, population-level transcriptome data from young

healthy pigs showed significant associations with mortality under a natural polymicrobial

disease challenge, implicating their possible use as early disease resilience predictors.

Funding from USDA-NIFA, Genome Canada, Genome Alberta, and PigGen Canada.

S24

Notes

S25

Metabolome analysis of host response to NDV infection under heat stress in two genetically distinct chicken inbred lines

Ying Wang1, Perot Saelao1, Kelly Chanthavixay1, Rodrigo A. Gallardo2, Terra Kelly2, Jack Dekkers3, Susan J. Lamont3, Huaijun Zhou1

1) Department of Animal Science, University of California, Davis, USA 2) School of Veterinary Medicine, University of California, Davis, USA 3) Department of Animal Science, Iowa State University, Ames, USA

Newcastle disease (ND), an endemic and devastating disease, and heat stress are two

major factors causing significant economic loss in poultry production in Africa. A better

understanding of the molecular mechanism of the effects of these two factors on host

responses will help develop novel prevention and treatment approaches. Liver metabolites

play an important role in maintaining overall homeostasis by influencing the organism's

physiology, metabolism, immunity, and overall health status. The objective of this study was

to identify specific metabolites and pathways associated with ND virus (NDV) infection and

heat stress in two genetically distinct highly inbred chicken lines.

Birds from two inbred chicken lines, Fayoumi and Leghorn, were exposed to environmental

temperature of 38°C for 4 hours at 14 days (d) of age, then 35°C until the conclusion of the

experiment. Non-treated individuals were kept at 29.4°C throughout the experiment. Heat

stressed birds were also challenged with the lentogenic NDV La Sota strain at 21d of age.

The results showed that Fayoumi had lower viral titers, higher antibody levels and are

relatively heat resistant with the treatment compared to Leghorns. To identify NDV and heat

stress associated metabolites, liver samples collected at 2 days post NDV infection were

used to perform Gas Chromatography-Mass Spectrometry (GC-MS) to identify the liver

metabolite profile. Statistical and functional analysis of the metabolomics data were analyzed

with MetaboAnalyst 4.0.

A total of 567 metabolites were detected, including 177 known metabolites and 390

unknowns. Overall, Leghorn birds had more metabolites presented at differential levels

between treatment groups compared to Fayoumi birds. Hexadecyl glycerol was the only

known metabolite identified with a significantly higher level in treated Fayoumi liver

compared to non-treated. Nine known metabolites had higher levels in treated Leghorn

birds, including fructose, aspartic acid, UDP-glucuronic acid, and phosphogluconic acid,

while three known metabolites had higher levels in non-treated Leghorns: conduritol-beta-

eposide, arachidonic acid, and aqualene. Several metabolite sets were significantly enriched

by these differentially altered metabolites in Leghorn birds, including glycolysis, fructose, and

mannose degradation, gluconeogenesis, and glutamate metabolism. These results suggest

that Fayoumi birds maintained better homeostasis by having fewer differentially expressed

metabolites than Leghorn birds, as Fayoumis are more resilient than Leghorns. Further

studies on biosynthetic pathways of the nine known metabolites in Leghorns would provide

more insights to understanding the biological functions of metabolites associated with NDV

infection during heat stress in chickens.

S26

Notes

S27

Causes and consequences of dog ownership: a register-based approach

Tove Fall

Uppsala University, Sweden

The relationship between humans and dogs is the longest of all the domestic animals. Dogs

have long been important as an extension to the human ‘toolkit’, assisting with various tasks

such as hunting, herding, and protection. The diverse roles that dogs fulfilled most likely

introduced a range of selective advantages to those human groups with domesticated dogs.

Inspired by assumed physical and psychosocial benefits of dog ownership, pet dogs are now

increasingly being used in interventions for the rehabilitation of prisoners, in-patient care and

during pediatric post-surgical care. A large number of studies have shown dog owners to be

more physically active, leading to acquisition of a dog being recommended as an

intervention to improve health. There is also evidence that dog-owners feel less lonely and

have an improved perception of wellbeing, particularly with regard to single people and the

elderly. However, well-designed and well-powered studies on the effects of dog ownership in

general has been lacking.

We have linked extracts from Swedish population and health registers and the Swedish Twin

Registry with individual-level data from two registers of dog ownership as well as one

insurance data base for dogs to investigate the causes and consequences of dog ownership

on a population-level scale.

I will present our data regarding the genetic contribution to dog ownership using a classical

twin design as well as socioeconomic determinants of dog ownership in the Swedish

context. I will also present results from our studies in children regarding a lower risk of

asthma (1), specifically in children exposed to female dogs (2), neutral risk for type 1

diabetes (3). I will also present our results showing that dog owners live longer (4).

Furthermore, I will show some preliminary results on the effects of death of the dog on risk of

acute cardiovascular event in the owner. However, all these studies have the limitation of

potential confounding from pre-existing differences personalities and health in those that

choose to acquire a dog, and more research in the field is needed, such as through genome-

wide association studies of dog ownership.

In summary, by linking national registers of health and demography with dog registers, we

are learning more about the potential health benefits from dog ownership.

References

1. Fall T, Lundholm C, Ortqvist AK, Fall K, Fang F, Hedhammar A, et al. Early Exposure

to Dogs and Farm Animals and the Risk of Childhood Asthma. JAMA Pediatr.

2015;169(11):e153219.

2. Fall T, Ekberg S, Lundholm C, Fang F, Almqvist C. Dog characteristics and future

risk of asthma in children growing up with dogs. Sci Rep. 2018;8(1):16899.

3. Wernroth ML, Svennblad B, Fall K, Fang F, Almqvist C, Fall T. Dog Exposure During

the First Year of Life and Type 1 Diabetes in Childhood. JAMA Pediatr. 2017;171(7):663-9.

4. Mubanga M, Byberg L, Nowak C, Egenvall A, Magnusson PK, Ingelsson E, et al. Dog

ownership and the risk of cardiovascular disease and death - a nationwide cohort study. Sci

Rep. 2017;7(1):15821.

S28

Notes

S29

Quantitative genetics of infectious diseases: integrating Indirect Genetic Effect

models with disease transmission models

Piter Bijma1 and Mart de Jong2

1Animal Breeding and Genomics & 2Quantitative Veterinary Epidemiology

Wageningen University and Research, The Netherlands

Infectious disease traits typically have low heritability, which may suggest limited

opportunities for genetic selection to reduce disease prevalence. However, classical

quantitative genetic analysis of binary diseases status (0/1, being infected/free) ignores the

transmission dynamics underlying individual disease status. Because an individual’s disease

status depends on its exposure to infectious herd mates, individual disease status is affected

by Indirect Genetic Effects (IGE). IGE are genetic effects of individuals on trait values of

other individuals, and have mainly been studied in the context of behavioural interactions. In

the context of infectious diseases, IGE occur because the probability an individual becomes

infected depends on the disease status of its herd mates and on their infectivity. Previous

studies on IGE revealed that they may create substantial genetic variance that is hidden to

classical quantitative genetic analysis. Here we connect quantitative genetic theory of IGE

with disease transmission models, aiming to identify the full heritable variance in the

prevalence of infectious diseases.

Results show that disease status (0/1) has substantially greater heritable variance than

currently believed. For example, in a SIS-model with genetic variation in susceptibility only,

the classical breeding value for disease status underestimates the impact of an individual’s

genes on disease prevalence in the population by a factor equal to the prevalence. For

example, for a prevalence of 30% (i.e., 0.30), selection of parents with a mean breeding

value of -0.04 suggest prevalence to decrease to 26% in the next generation. However,

because of positive feedback effects in disease transmission, true prevalence decreases to

0.30 – 0.04/0.30 = 17%. This result implies that infectious disease prevalence can, in

principle, show much greater response to selection than currently believed (even without

genetic variation in infectivity).

To make the full variance in disease traits visible to breeders, we propose a total breeding

for disease prevalence, which includes the effects of feedback dynamics. As an alternative,

we present a breeding value for the basic reproduction number, R0, which may be preferred

by epidemiologists. The latter also gives an indication of the selection effort required to

eradicate an infectious disease from a population or herd. Hence, we argue that breeders

should become familiar with R0. Furthermore, we show that selection based on data where

disease transmission occurs within groups of related individuals (“kin selection”)

considerably increases response to selection. Overall, our results suggest that selection

against (endemic) infectious diseases is more promising than currently believed.

S30

Notes

S31

Gene co-expression in the chicken thymus reveals unique responses to lipopolysaccharide and acute heat stress

Melissa S. Monson 1, Angelica G. Van Goor 1, Max F. Rothschild 1, Carl J. Schmidt 2 and Susan J. Lamont 1

1 Department of Animal Science, Iowa State University, Ames, IA 50011, USA 2 Department of Animal and Food Sciences, University of Delaware, Newark, DE 19716, USA

Bacterial diseases of poultry can reduce bird health and performance, economically impact

the industry, and threaten food safety. Heat stress can further increase chicken susceptibility

to these infectious diseases. Understanding how chicken immune tissues, such as the

thymus, respond to infection and how these responses change under heat stress will be

needed to improve host resistance. Co-expression network analyses of the transcriptome

can identify genes and pathways central to these responses. In this study lipopolysaccharide

(LPS) was used as an immune stimulus and proxy for bacterial infection. Age-matched birds

(22 days of age) from a Fayoumi line (disease and heat resistant) and a broiler line (disease

and heat susceptible) were exposed to LPS (100 µg/kg) and/or acute heat stress (35°C) in a

2 x 2 design. RNA-sequencing (RNA-seq) was used to characterize the thymic transcriptome

in each of these birds (n = 3-4 libraries/injection/temperature/line). After mapping to the

chicken genome (Galgal6a), variance stabilized read counts for more than 15,000 genes

were used for weighted co-expression network analysis (WGCNA). Fifteen modules of co-

expressed genes were identified, of which six modules were significantly associated with

line, exposure to LPS, or heat stress. Functional analysis revealed that LPS-associated

modules contained genes involved in nitrogen oxide synthesis, fibrinogen-mediate cell

adhesion, and cytokine signaling, while heat-associated modules contained developmental,

Wnt signaling and actin-related genes. Overall, the significant modules from co-expression

analyses revealed pathways involved in the response to LPS and heat stress within the

chicken thymus and can provide targets for future research to reduce susceptibility to heat

and infectious disease. USDA-NIFA-AFRI Climate Change Award #2011-67003-30228; the

USDA National Institute of Food and Agriculture, Hatch project #5358.

S32

Notes

S33

How to predict that some animals respond better to vaccination than others: application to vaccination against Mycoplasma hyopneumoniae in pigs

Fany Blanc1, Jordi Estellé1, Gaëtan Lemonnier1, Jean-Jacques Leplat1, Yvon Billon2, Olivier Bouchez3, Marie-Noëlle Rossignol1, Jean-Pierre Bidanel1, Marie-Hélène Pinard-van der Laan1 and Claire Rogel-Gaillard1

1 GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France 2 GenESI, INRA, 17700 Surgères, France 3 GeT-PlaGe, INRA, 31326 Castanet-Tolosan, France

Our aim was to study whether host genetic variability can influence vaccine responses and

be considered to improve vaccine strategies. We focused on the vaccine response to

Mycoplasma hyopneumoniae (M. hyo) in pigs and searched for genetic markers and blood

biomarkers predictive of vaccine response intensities. Large White pigs (48 families, 186

animals) were vaccinated at weaning (around 28 days of age) with a booster vaccination

three weeks later (commercial inactivated vaccine). Seric M. hyo-specific IgGs were

measured at three time points corresponding to early response (just before booster, 21 days

post-vaccine (dpv)), maximum response intensity after the booster vaccination (28 or 35

dpv), or long-term IgG persistence (118 dpv). Genome-wide association studies with a 658K

SNP chip revealed a candidate genomic region on SSC4 associated with early vaccine

responses at 21 dpv. In parallel, RNAseq data from blood sampled before vaccination were

produced for a subset of 92 piglets that were ranked according to the M. hyo-specific IgG

levels. At each time point, high and low responders were selected and sparse Partial Least

Squares-Discriminant Analyses (sPLS-DA) were carried out to identify the best predictive

blood biomarkers that classify animals into each group. We detected 94 candidate genes

that were predictive with an accuracy higher than 99% for the three time points.

In conclusion, we show that specific IgG production after vaccination against M. hyo is under

genetic control and provide proofs of principle that blood biomarkers measured prior

vaccination can predict individual vaccine response levels. We designed a custom

OpenArray for high-throughput RTqPCR assays to test our list of candidate biomarkers in

validation populations.

S34

Notes

S35

Novel insights on Salmonella colonization and persistence in poultry intestinal tract

Huaijun Zhou1, Khin K. Z. Mon1, Yael Litvak2, Andreas Baumler2

1Department of Animal Science, 2Department of Medical Microbiology and Immunology,

University of California, Davis, USA

Salmonella Enteritidis (SE) is a zoonotic enteric pathogen that is most frequently associated

with diarrheal disease in humans while chickens serve as asymptotic carrier. The avian

gastrointestinal (GI) tract is home to complex and diverse bacterial populations that provide

many beneficial functions to host, which includes conferring colonization resistance against

the invading pathogenic microorganisms. Maintenance of overall gut homeostasis in chicken

host involves the role of the gut microbiota, its functional activities, and host metabolites.

During the critical period of establishing stable presence of balanced microbial community

members, exposure to pathogen like SE could have detrimental effect not just on the gut

microbiota but also its activities and metabolites in the intestinal environment. The three-way

interaction between the host, resident gut microbiota and pathogen during SE infection in

day-old and two-week old layer chicks were examined. SE infection in day-old chicks

significantly reduced the overall diversity of the microbiota population with expansion of

Enterobacteriaceae family. The impact of SE infection on microbial communities was more

substantial in the late stage of infection. While following SE infection at two-week old chicks,

the results revealed enriched colonization by non-specific minority members of the

community. Furthermore, we show that neonatal chick colonization with SE required a

virulence factor-dependent increase in epithelial oxygenation, which drove pathogen

expansion by aerobic respiration. Unlike in mice, cytochrome bd oxidase provided the

largest fitness advantage under microaerobic conditions for SE colonization in chicks. Co-

infection experiments with an E. coli strain carrying an oxygen-sensitive reporter suggested

that SE competes with commensal Enterobacteriaceae for oxygen. A combination of

Enterobacteriaceae and sporeforming bacteria, but not colonization with either community

alone, conferred colonization resistance against SE. These results suggest that commensal

Enterobacteriaceae contribute to colonization resistance by competing with SE for oxygen.

Combining spore-forming bacteria with a probiotic E. coli isolate protected germ-free mice

from pathogen colonization, but protection was lost when the ability to respire oxygen under

microaerophilic conditions was genetically ablated in E. coli. These results suggest that

commensal Enterobacteriaceae contribute to colonization resistance by competing with SE

for oxygen, a resource critical for pathogen expansion in chicks.

S36

Notes

S37

Resistance and resilience of livestock to arbovirus infections

Massimo Palmarini

MRC-University of Glasgow Centre for Virus Research, Glasgow, UK

Infections by the same pathogenic virus can result in variable clinical outcomes in different

hosts, from subclinical infections to fatal disease, yet we lack understanding of the

mechanisms underlying such remarkable differences. Variances in the clinical outcome of

viral disease largely result from differences in virus-host interactions. These interactions are

inherently complex as they are influenced by the genetic variability of both virus and host.

Within a virus species, some strains are more “virulent” due to differences in the viral

genome that confer distinct phenotypes. Moreover, the genetic makeup of viruses can

change rapidly, with mutations allowing gain or loss of virulence. Similarly, differences in the

genetics of animal species (or of individuals within the same species) also influence

susceptibility or resistance to disease, and over longer evolutionary periods, the host

genome may also change in order to better withstand specific pathogenic insults.

Thus, as virus-host co-evolution clearly shapes disease outcome, natural models of disease,

in which virus and host responses to infection can be simultaneously probed, are invaluable

tools for accurate mechanistic dissection of virus pathogenesis.

This talk will focus on the mechanisms of viral pathogenesis in bluetongue, a vector-borne

disease caused by bluetongue virus (BTV). Bluetongue outbreaks have a major impact on

animal health and the agriculture sector. BTV can infect essentially all domestic and wild

ruminant species but clinical symptoms vary considerably. In some animals, BTV infection

results only in mild fever while others suffer haemorrhagic fever and death. Sheep are more

susceptible to clinical disease, while goats and cows are more “resilient” to BTV infection, as

they develop high levels of viremia and can be reservoirs of infection, but rarely show clinical

signs. Data will be presented on how the complex balance between virus replication, the

host type-I IFN response and adaptive immunity determines the clinical fate of BTV infection.

S38

Notes

S39

A CCR5 promoter variant increases susceptibility to arthritis encephalitis virus in goats

Acutis Pier Luigi, Colussi Silvia1, Desiato Rosanna1, Beltramo Chiara1, Peletto Simone1, Modesto Paola1, Maniaci Maria Grazia1, Campia Valentina1, Quasso Antonio2, Rosati Sergio3, Bertolotti Luigi3, Ru Giuseppe1

1Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Torino, Italy; 2Department of Prevention ASL AT, Asti, Italy; 3Department of Veterinary Science, University of Turin, Grugliasco (TO), Italy.

The small ruminant lentiviruses (SRLVs) are a heterogeneous group of viruses that includes

caprine arthritis encephalitis virus (CAEV) and Maedi-Visna virus (MVV). SRLVs affect the

production and welfare of sheep and goats worldwide. Currently no effective treatment and

vaccine are available, making innovative control measures necessary.

A variant of the chemokine (C-C motif) receptor 5 (CCR5) gene is reportedly involved in

resistance to human immunodeficiency (HIV) infection in humans and to SRLV in sheep.

A cross-sectional study in goats was carried out to investigate the role of CCR5 genetic

variants in controlling susceptibility/resistance to CAEV.

The variant g.1059T located in the promoter region revealed an interesting association with

high proviral loads (a 2.8-fold increased risk). This could be explained with an alteration of

the transcriptional level; overexpression of the CCR5 receptor on the cell surface may

increase virus internalization and proviral load as a consequence.

Our findings could be advantageously used to reduce the susceptibility of goat herds to

CAEV by negatively selecting animals carrying the g.1059T mutation. Eliminating animals

predisposed to high proviral loads could also limit the development of clinical signs and the

spread of the virus, since these animals are also highly efficient in shedding the virus.

S40

Notes

S41

Chicken STAU2 Protein Interacts with NS1 and Is Required for the Replication of H5N1 Influenza Avian Virus

Qiao Wang, Qinghe Li, Fei Wang, Ranran Liu, Maiqing Zheng, Jie Wen and Guiping Zhao

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences

Materials

Viruses: Highly pathogenic H5N1 strain A/mallard/Huadong/S/2005(YS)

Cells: Chicken DF1 embryonic fibroblast cells and MDCK (Madin-Darby canine kidney) cells

Result

H5N1 influenza A virus (IAV) is seasonal epidemics and reoccurring pandemics, which

represents a worldwide threat to public health. Nonstructural protein 1（NS1）protein is

encoded by viral segment number eight, which is a virulence factor of IAV(Fukuyama et

al.,2011). Staufen double-stranded RNA binding protein 2 (STAU2) is a member of the

family of double-stranded RNA (dsRNA)-binding proteins involved in the transport and

localization of mRNAs to different subcellular compartments and organelles(Bélanger et al.,

2003). In the current study, we found that STAU2 interacted with NS1 protein of H5N1 IAV.

Knockdown of STAU2 significantly decreased the titer of H5N1 IAV in chicken cells and was

accompanied with attenuated production of proinflammatory cytokines. Further, we found

that STAU2 promoted the NS1 mRNA export of H5N1 IAV from nucleus to cytoplasm. As an

anti-apoptotic protein, STAU2 can promote viral replication through inhibiting cell apoptosis.

IAV infection down-regulated STAU2 expression in chicken DF1 cell line, which may be due

to the suppression of the ATR signaling pathway by the IAV infection.

Discussion

As an interacting factor of NS1, STAU2 could promote the NS1 mRNA export of H5N1 IAV

from nucleus to cytoplasm. The expression of STAU2 is regulated by the ataxia

telangiectasia and Rad3-related (ATR) signaling pathway(Zhang et al., 2016). IAV infection

downregulated STAU2 expression in chicken DF1 cell line, which may be due to the

suppression of the ATR signaling pathway by the IAV infection. STAU2 is an anti-apoptotic

protein that involved in genome maintenance(Zhang et al., 2016) which implied that STAU2

promoted the IAV replication by maintaining the stability of the host genome and inhibiting

the apoptosis of host cells, which is essential for virus replication.

Keywords: H5N1; NS1; STAU2; Chicken; DF1; mRNA export

S42

Notes

S43

Listening to your inner goddess: a spontaneous SCID pig as an emerging model for

cancer and regenerative medicine research

Christopher K. Tuggle1, Adeline Boettcher1, Ellis Powell1, Yunsheng Li1, Sara Charley1,

Zoe Kiefer1, Kristen Byrne2, Amanda Ahrens1, Joan Cunnick1, Crystal Loving2, Mary

Sauer1, Kathleen Mullin1, Jack C.M. Dekkers1, Jason W. Ross1

1Iowa State University, Ames, IA, USA

2USDA-ARS, National Animal Disease Center, Ames, IA, USA

Severe Combined Immune Deficient (SCID) mice have been used for many years in

xenograft research because the lack of an adaptive immune system permits the growth and

subsequent study of human cells in an in vivo environment. However, rodents are an

imperfect model for several aspects of human biology. On the other hand, the domestic pig

has anatomical, physiological, and genomic similarities to humans that provide significant

value as an alternative to rodent models. Further, SCID pigs have been reported, including

the spontaneous SCID pig at Iowa State University (ISU). I will describe the serendipitous

discovery and characterization of the ISU SCID pig, which has been shown to contain

mutations in the Artemis gene, named for the Greek goddess of the hunt, childbirth, and the

protector of small children. Artemis is required for normal DNA repair, including somatic

recombination necessary for B and T lymphocyte production, and thus Artemis mutations

cause a T-B-NK+ immunodeficiency. I will also discuss our new research studies and

husbandry protocols for maintaining these highly disease susceptible animals in strict

biocontainment. These methods have successfully maintained specific pathogen free SCID

pigs for up to 6 months (>100 kg). The ISU SCID pig has been successfully used to study

innate-adaptive response to pathogens, grow several types of human cancers, and study

engraftment of human skin. We have also used CRISPR/CAS9 approaches to generate a

second-generation SCID model by mutating the IL2RG gene, validating its T-B-NK-

phenotype, and have begun experiments to humanize these new SCID pigs. Our studies

have established SCID pigs as a valuable large animal xenograft model.

S44

Notes

S45

Molecular innovation and conservation across mammalian organ development

Margarida C. Moreira

Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, Germany

Mammals exhibit a remarkable diversity in organ morphology and physiology. Identifying the

genetic and developmental bases of this diversity will greatly advance our understanding of

phenotypic evolution and the developmental and evolutionary underpinnings of human

disease. Gene expression provides a molecular read-out of developmental processes and

therefore a window into the genes and regulatory networks underlying organ development. I

will describe a new evo-devo resource consisting of developmental gene expression time

series for seven major organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis)

from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit,

opossum and chicken. Using the developmental time series we established stage

correspondences for all species throughout development, which provided the basis for

evolutionary comparisons and revealed pronounced heterochronies in the gonads. We found

that although globally, developmental programs are conserved across mammals, the

conservation is not uniform across organs and that it notably changes throughout

development. Species transcriptomes are most similar at the earliest developmental stages

and then progressively diverge. This matches the increase in morphological divergence

observed between species with developmental time described by von Baer already in the

19th century. We find evidence that this pattern is driven by the high pleiotropy of the genes

employed early in development, which imposes strong constraints on evolution. As organs

differentiate and mature, the genes employed have increasingly lower pleiotropy, thereby

decreasing constraints and increasing the opportunities for evolutionary change.

Evolutionary change is driven by the deployment of lineage-specific genes and by the

evolution of new developmental trajectories in pre-existing genes. We identify hundreds of

genes with novel developmental trajectories in each of the organs, which are strong

candidates for underlying lineage-specific morphological and physiological phenotypes. Our

work furthers our understanding of the genetic and developmental foundations of the

evolution and phenotypic diversity of mammals.

S46

Notes

S47

Different transcriptional response of susceptible and resistant fish hints at the mechanism of KHV disease resistance in carp

Lior David1, Roni Tadmor-Levi1, Adi Doron-Faigenbaum2, Gideon Hulata2

1Department of Animal Sciences, R.H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel; 2Agricultural Research Organization , Bet Dagan, Israel

Infectious diseases are challenging fish production and further development of aquaculture.

Disease resistant strains is a desired sustainable solution to this problem. Identifying the

mechanism conferring resistance is important for enhancing breeding of resistant strains and

for understanding the function of bony-fishes immunity. Cyprinid herpes virus-3 (CyHV-3) or

Koi herpes virus (KHV) is damaging production of common carp, one of the top produced

fish worldwide. Applying family selection, we have been developing genetically resistant and

susceptible carp strains. By analyzing viral loads in host tissues during infection and

disease, we found that resistant fish restrain the viral spread in their bodies better than

susceptible fish, suggesting that in this case, resistance reflects a difference in their immune

response. To further understand the resistance mechanism, RNAseq was applied to

characterize the transcriptomic response to infection in the spleen of susceptible and

resistant fish. Distinct transcriptional profiles were found for susceptible and resistant fish at

day 0 before infection, reflecting genetic background differences. More importantly, a distinct

transcriptional response to infection was elicited between these fish types. In susceptible

fish, over four times more differentially expressed genes were up-regulated between days 0

and 4 to infection compared to resistant fish. Up-regulated genes in susceptible fish were

significantly enriched for typical interferon mediated response. Up-regulated genes in both

susceptible and resistant fish were enriched for leukocyte migration genes but different sets

of chemokines were elicited by each fish type. Chemokines are a large gene family with

multiple homologs in bony-fishes and with specific paralogs in the duplicated genome of the

common carp. Interestingly, some degree of functional divergence in expression levels due

to infection was observed between homologs of these chemokines and also between carp-

specific paralogs. Analyses of further time points for specific genes from these pathways

indicated that resistant fish mount a neutrophil-assisted response that susceptible fish were

lacking. Results of our transcriptomic approach are concordant with the differences in viral

loads and mortality between these fish types. Our results highlighted some genes and

pathways, which are part of the disease resistance mechanism.

S48

Notes

S49

The discovery of chicken TNF-α proves that “missing genes” not necessarily must remain missing

Nina B. Burkhardt*, Franziska Rohde*, Benjamin Schusser°, Tomáš Hron^, Helena Farkašová^, Jiří Plachý^, Sonja Härtle*, Jiří Hejnar^, Daniel Elleder^, and Bernd Kaspers*

*Department of Veterinary Science, Ludwig-Maximilians-Universität, Munich, Germany °Reproductive Biotechnology, Department of Animal Sciences, Technical University Munich, Munich, Germany ^Laboratory of Viral and Cellular Genetics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia

Since the publication of the first chicken genome sequence, the scientific community

encountered the mystery of genes playing key roles in mammalian immunology, but being

seemingly absent in birds. The jutting acceleration of technical and bioinformatic progress in

fields of deep sequencing and advanced data mining allows us to have an increasingly

closer look into the chicken genome nowadays.

By making use of these new achievements, we recently discovered a long-missed cytokine

in chickens and other avian species, TNF-α. TNF-α is one of the first cytokines that was ever

discovered, and it is of superior importance as a diagnostic tool on one hand, and also as a

target for immunotherapy of certain immune-mediated diseases, like rheumatoid arthritis and

Crohn's disease, on the other hand. In spite of the decade-long research on human and

other species' TNF-α, we were the first to describe a full-length avian gene sequence. We

analyzed its homology to known TNF-α sequences and to other members of the TNF family

and identified a syntenic locus. Furthermore, ex vivo as well as in vivo induction of chTNF-α

mRNA was demonstrated in response to stimuli known as triggers of mammalian TNF-α

expression, like LPS-administration and TCR-crosslinking. Finally, functional studies on an

NFκB-reporter cell line proved biological activity of recombinant chicken TNF α.

Here, we present new in vitro and ex vivo data, that further establish the role of chicken TNF

α in the complex network of the immune response. We used established reporter cell lines to

assess protein functionality as well as primary cells in order to gain deeper insight in gene

expression of chicken TNF-α, herein setting a focus on activation of macrophages by TNF-α

stimulation and their subsequent immune response. Thereby, we further characterize the

biological function of chicken TNFα and underline its importance for avian immunology

research.

S50

Notes

S51

Whole genome sequencing to untangle transmission and antimicrobial resistance of

zoonotic pathogens

Alison Mather

Quadram Institute Bioscience, UK

Whole genome sequencing (WGS) currently provides the greatest molecular resolution

available to study how bacteria evolve and how they differ from each other. In order to

control the spread of pathogens and antimicrobial resistance (AMR), it is essential to

understand where they arise and how they spread between populations, but bacterial

evolution and biology are complex. With the decreasing cost of WGS, genomic epidemiology

to untangle the sources, reservoirs and transmission pathways of bacterial pathogens and

AMR is possible. In addition, the use of long-read sequencing and metagenomics is allowing

deeper investigation of the factors related to bacterial success. In my talk, I will describe how

sequencing and genomic epidemiology have been applied to bacteria from different settings

and in multiple host populations, and the insight this has provided on the origin and spread

of the bacteria and AMR and also to understand the relative importance of different host

populations to the overall burden of disease.

S52

Notes

S53

The changing genome of Influenza A Viruses

Holly Shelton

The Pirbright Institute, UK

Influenza A Viruses can cause disease in multiple species including humans and poultry.

The economic and public health repercussions of influenza A virus outbreaks is significant

world-wide. Influenza A viruses have a segmented genome which permits dramatic viral

genetic changes through reassortment, in addition the RNA-dependant RNA polymerase of

the virus has no proof-reading activity so on average a single nucleotide error is made every

time the genome is copied to produce progeny. Reassortment and error-prone replication

facilitates rapid and continuous genetic change in the viral genome which results in influenza

A viruses having many different phenotypes and host tropisms. H9N2 is an avian influenza

strain that is endemic in poultry over vast swathes of Asia and the Middle East.

Reassortment between H9N2 and a highly pathogenic H7N3 virus in 2008 resulted in the

circulating H9N2 strain becoming increasingly pathogenic in poultry. In 2013 in China H9N2

reassorted with other low pathogenic subtypes of avian influenza resulting in the H7N9 strain

which quickly established wide-spread outbreaks in poultry in China and crossed the species

barrier from poultry to humans with increased frequency than other avian influenza viruses

resulting in the severe infection of more than 1500 humans. The continuous circulation of the

low pathogenicity H7N9 strain in chickens over has resulted in the development of a

pathogenicity motif in the virus that means there is now highly pathogenic H7N9 viruses

circulating. Using this example the impact of genetic changes on viral replication and the on

the tools utilised to control viruses in poultry will be examined.

S54

Notes

S55

Directed Genome Evolution to identify bacterial genes for phagocyte survival in a BCO hypervirulent isolate.

Douglas D. Rhoads, Abdulkarim Shwani, Sura Zaki

Program in Cell and Molecular Biology; University of Arkansas; Fayetteville, AR, USA

The aim of our study is to identify bacterial genes responsible for survival in, and killing of,

chicken macrophage. We have been investigating the pathogenicity of an isolate of

Staphylococcus agnetis obtained from lame birds on our research farm. The isolate was

from femoral head necrosis samples from broilers induced for lameness by growth on

suspended wire flooring. All evidence suggests this hypervirulent strain developed through

repeated experiments inducing high incidence of lameness; primarily Bacterial

Chondronecrosis with Osteomyelitis (BCO). Isolate 908 is capable of inducing 50% BCO

lameness by 56 days in birds on litter, when administered as a single dose in drinking water

at 20 days of age. The BCO infection is readily communicable to other birds in the same

facility. We compared our chicken isolate 908 to S. agnetis isolates from mastitis in dairy

cattle for bacterial killing assays in an immortalized chicken macrophage line. The cattle

isolates are rapidly killed but isolate 908 not only survives after phagocytosis, it kills the

macrophage within 2 days; even at low multiplicity of infection (MOI). We have sequenced

and assembled genomes for 9 cattle isolates, and isolate 908. Phylogenetic trees

demonstrate that isolate 908 clusters within the cattle isolates. We have been using Directed

Genome Evolution to identify the genetic basis of macrophage survival and killing. This

involves transforming DNA from isolate 908 into a closely related cattle isolate (1379). The

transformants are then passaged through chicken macrophage to select for survival and

macrophage-killing. Multiple transformations have indicated that the survival and killing

activity appears to reside on one or more episomes in isolate 908. Genome assemblies of

the selected transformants demonstrate that multiple transposable elements can be

transferred which complicates our analyses. We have generated ten independent

transformants to clarify the exact determinants for macrophage killing. Those genomes are

currently being sequenced to precisely identify the necessary genes for macrophage killing.

Our model is that isolate 908 is hypervirulent in chickens because it has obtained

determinants that allow it to survive phagocytosis and colonize weak areas in the chicken

vascular system, specifically the rapidly growing proximal growth-plates of the long leg

bones, leading to BCO lameness. Defining these virulence systems will help us design

management and selection strategies to reduce BCO lameness in broilers.

S56

Notes

S57

Exploring the impact of oxytetracycline on gut microbiome homeostasis in rainbow trout (Oncorhynchus mykiss, W. 1792)

Christopher J. Payne, Simon MacKenzie, Margaret Crumlish

Institute of Aquaculture, University of Stirling, FK9 4LA, Scotland, UK

The vertebrate intestinal environment is colonised by a complex microbiome community

which plays a critical role in host physiology and health (Colston & Jackson et al. 2016).

Antibiotic compounds have recently been reported to induce significant alterations in the

microbiome communities of higher vertebrates (Videnska et al. 2013; Vickova et al. 2016).

However, the impact of antibiotics in fish remains relatively unexplored. This is concerning

as intensification within the global aquaculture sector has led to an increase in disease

outbreaks and reliance on chemotherapeutants as a critical approach for treating infections

in production systems (Pérez-Sánchez et al. 2018). As certain members within the

microbiome community are thought to provide beneficial services to their host (Gómez &

Balcázar 2008), any modification in the microbiome community through antibiotic exposure,

could alter this highly complex host-microbiome relationship. The following study therefore

explored the effect of oxytetracycline (OTC), a broad-spectrum antibiotic licensed for use in

UK aquaculture, on the gut microbiome composition in farmed rainbow trout. In this study,

rainbow trout (n=39) at 152.8 ± 8.9g were exposed to a therapeutic dose of OTC,

administered in the feed over seven days, followed by a 14-day withdrawal period. Gut

digesta from both control (non-medicated feed) and treated fish was harvested immediately

before OTC administration, and then at days 2, 8, 10, 14 and 21 of the experiment. The

dynamic changes in microbiome composition before, during and after OTC treatment was

then characterised using amplicon-sequencing of the bacterial 16S rRNA gene. Next, the

influence of OTC on gut microbiome stability and resilience in farmed rainbow trout will be

evaluated using alpha and beta diversity analysis, and by comparing bacterial community

profiles between control and treated groups. Following this, analysis of microbial networks

and predicted KEGG pathways will be performed to investigate the impact of OTC on

interspecies interactions and identify any changes in microbiome-mediated functions within

the fish host. Results from this study will help towards developing better management

strategies for fin-fish aquaculture by providing a more detailed profile of the changes in

microbiome community composition and host/microbiome interactions in response to

antibiotic compounds.

S58

Notes

S59

Insights from understanding genetic drivers of the variable immune response into

human disease

Julian Knight

University of Oxford, UK

In this talk I will describe how genetic variation impacts the immune response in health and

disease. Rare variants resulting in Mendelian traits have been highly informative in

understanding immune function. For more common alleles, robust disease associations

have been established with different immune traits but determining the functional basis for

these associations remains challenging. I will discuss how we have adopted a genetics-led

approach to study alleles modulating innate immunity, showing how such analysis has

revealed the extent of variation in immune gene expression observed in healthy populations

as well as insights into the dysregulated response seen in disease. I will describe our work

involving expression quantitative trait mapping for different leukocyte cell populations

including specific conditions of innate immune activation which reveal widespread and

substantial differences in response between individuals. I will show how defining local and

distant associations can be informative for resolving regulatory variants. I will relate this to

the underlying epigenetic landscape and other functional annotations. I will show how we

have adopted a similar approach in sepsis to understand the dysregulated host immune

response seen in such patients which defines specific disease endotypes and is enabling a

precision medicine approach. I will also describe our ongoing work using evidence for

functional alleles and specific modulated genes as part of a genetics-led approach to drug

target validation, demonstrating the importance of considering network interactions and

pathways to maximise informativeness. I will discuss different types of evidence and

experimental approaches that can be used to validate such a genetics-led approach to target

prioritisation as well as broader insights into disease pathogenesis.

S60

Notes

P1

Poster Presentations

Investigation of resilience indicators based on body weight variation in chickens

Tom V.L. Berghof1, Henk Bovenhuis1, Joop A.J. Arts2, Francois Karangali1, Jan J. van der Poel1, Henk K. Parmentier2, Han A. Mulder1

1 Wageningen University & Research Animal Breeding & Genomics, The Netherlands 2 Wageningen University & Research Adaptation Physiology, The Netherlands

Resilience is the capacity of an animal to be minimally affected by disturbances or to rapidly

return to the state pertained before exposure to a disturbance. Less resilient animals are

expected to be more susceptible to environmental perturbations, such as diseases, and will

consequently show more fluctuations in production than more resilient animals. The

objective of this research was to investigate genetic parameters of resilience based on body

weight (BW) variation, and to investigate its relation with natural antibody (NAb) levels. NAb

are antibodies recognizing antigens without previous exposure to these, and are

hypothesized to be an indication of general disease resistance. BW data of individuals

selectively bred for high and low NAb levels were collected on a four-weekly interval until

around 32 weeks of age. In addition, keyhole limpet hemocyanin (KLH)-binding total, IgM

and IgG NAb were measured (n = 8,713). Standardized residuals of individual's BW

compared to lines' average BW were used as an estimate for resilience by calculating: 1. the

ln-transformed variance of the residuals (n = 1,573), the skewness of the residuals (n =

1,573), and the lag-one autocorrelation of the residuals (n = 1,463). Heritabilities were 0.10

for variance, 0.09 for skewness, and 0.09 for autocorrelation, showing heritable variation in

these resilience indicators. Genetic correlations between the three resilience indicators were

between |0.07| and |0.40|, suggesting that the resilience indicators capture different parts of

resilience. Genetic correlations between resilience indicators and NAb were not significantly

different from 0, which may indicate that the resilience indicators and NAb capture different

aspects of (disease) resilience, or that there was a lack of disease occurrence to show

common genetic variation. Nevertheless, the relatively high heritabilities of resilience

indicators based on BW offer opportunities for further study, such as quantifying the

predictive value of these resilience indicators for the response to environmental

perturbations.

P2

Early changes in the nasal microbiota of piglets at weaning can predispose the animals to suffer Mycoplasma hyorhinis systemic infection

Miguel Blanco, Florencia Correa-Fiz, Marina Sibila, Virginia Aragón

IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB)

Modifications in husbandry and improvement in productivity have coincided with increasing

problems of fibrinous or fibrino-purulent polyserositis, arthritis and meningitis, mainly in

nursery piglets. The differential diagnosis of these clinical signs should include Haemophilus

parasuis (Hp, aetiological agent of Glässer's disease), Streptococcus suis (Ss) and

Mycoplasma hyorhinis (Mhr) infection. The role of this latter microorganism in clinical

disease is often questioned because of its ubiquitous distribution in the upper respiratory

tract of the pigs and its association with concomitant infections, such as Hp and Ss. The

duality of these bacteria as commensals and pathogens is also an important aspect when

elucidating their role in disease. In addition, the interaction with other members of the nasal

microbiota should be considered. Thus, the goal of this study was to examine the role of the

nasal microbiota composition for Mhr disease development.

The role of Mhr in polyserositis was supported by its detection by qPCR/ isolation from

systemic lesions in 15 cases, where Hp and Ss were not found. From these 15 cases where

polyserositis by Mhr was diagnosed, two farms were selected for the microbiota study. In

addition, six control farms with good health status (clinically healthy) were included in the

study as controls. Nasal swabs were taken from 6-10 piglets at weaning from each farm and

total DNA was extracted. The hypervariable region (V3-V4) from 16S rRNA gene was

sequenced using Illumina (MiSeq) sequencing platform. Qiime2 software was used to

perform the in silico analysis of microbiota composition. Samples belonging to good health

status farms presented higher mean observed OTUs and alpha diversity (estimated through

Shannon index) than samples from farms with Mhr clinical infection. Principal component

analysis was done to evaluate beta diversity using both Jaccard and Bray-Curtis distances.

Differential clustering was observed between samples from the Mhr-cases and the control

farms.

In summary, the nasal microbiota at weaning may be a predisposing factor for the

subsequent development of polyserositis by Mhr in nursery piglets, as it has been

demonstrated for Glässer's disease. Further studies will be needed to understand how the

nasal microbiota colonizers may influence pig health status.

P3

The transcriptional landscape of whole blood in cattle: primiparous vs multiparous

Laura Buggiotti1, Zhangrui Cheng1, Mazdak Salavati2, Haruko Takeda3, Claire Wathes1 and Genotype plus Environment Consortium4

1Royal Veterinary College, London, United Kingdom; 2The Roslin Institute, Edinburgh, United Kingdom; 3University of Liège, Liège, Belgium; 4Ghent University, Brussels, Belgium

Recent studies in human population have highlighted age-associated changes in leucocyte

functionality affecting innate and adaptive immune functions. In cattle, milk production

capacity increases with lactation number, moreover, metabolic profiles in early lactation

differ between older and younger cows. Both of the latter aspects are likely to influence how

cows are able to deal with both infections and metabolic imbalances at different stages of

their lives. The aim of this study was to compare gene expression profiles of whole blood

samples obtained in early lactation and classified according to lactation number.

A total of 229 cows (53 primiparous -PP, and 176 multiparous -MP) were recruited from

experimental farms and blood samples were drawn from the tail vein. Average 30 million

single end reads of 75 nucleotides length per sample were produced using Illumina NextSeq

500 sequencer. Reads were trimmed according to base quality, Bos taurus assembly

(UMD3.1.1) and its corresponding gene set was used as reference to map reads by the

splice aware aligner HISAT2. BAM files were further processed with Picard Tools in order to

remove PCR duplicates. Reads per gene were counted with StrigTie. The 229 cows were

divided into three age groups: i) young, (53 - PP), ii) medium (121 - MP 2-3), iii) old (55, MP

>3). Differential gene expression analysis was conducted with DESeq2 and contrast was

young versus old. Herd effect was considered and removed using limma. Out of 17,216

genes over 5K were found to be differentially expressed (padj <0.1), narrowed it down to

2,925 by considering only the ones with padj <0.01 between young and old. GO enrichment

analysis highlighted process involved in the immune system and fc-gamma signaling which

has an immunoglobulin region. Pathway enrichment analysis (GAGE) showed that many key

inflammatory pathways were up-regulated in older cows, signalling through IL-17, TLR,

NOD-like receptors and TNF. Metabolic differences in the young cows were reflected by up-

regulation of pathways for fat digestion and absorption. This preliminary analysis highlights

that older cows have increased expression of genes regulating inflammatory pathways, and

further investigation is needed to better understand the age-associated changes between

primiparous and multiparous cows.

P4

Updating the annotation of the SLA complex from the genome assembly Sscrofa 11.1

Mathieu Charles (1), Ben Rosen (2), Hamid Beiki (3), Christopher K. Tuggle(3), Joan K. Lunney (4), Claire Rogel-Gaillard (1)

1 GABI, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France 2 Animal Genomics and Improvement Laboratory, BARC-EAST, ARS, USDA, Beltsville, MD, USA 3 Iowa State University, Department of Animal Science, Ames, IO, USA 4 Animal Parasitic Diseases Laboratory, BARC, ARS, USDA, Beltsville, MD, USA

We report here the annotation of the pig Major Histocompatibility Complex (MHC) referred to

as the Swine Leucocyte Antigen (SLA) complex from the latest reference pig genome

assembly Sscrofa11.1. The MHC is a large genomic region that comprises the highly

polymorphic series of class I and class II SLA genes involved in peptide presentation and

self-recognition, together with evolutionarily conserved anchor genes that have immunity-

related and other functions. The SLA is a key genomic region involved in innate and

adaptive immunity. The gene clusters form haplotypes, which are mainly classified according

to allelic diversity of polymorphic exons of MHC genes. To characterize the SLA complex

and study its diversity, we need to annotate the genes present in the region and finely

characterize the MHC gene series that vary in number and in alleles according to

haplotypes. The SLA complex maps to SSC7 and is split by the centromere, the class I and

III sub-regions mapping to 7p1.1 and the class II sub-region to 7q1.1. The SLA haplotype

Hp1.1 has been fully sequenced; it spans 2.4 megabases including 151 annotated loci

(Renard et al., Genomics, 2006). Several other haplotypes have been partially sequenced

but not the entire complex. The availability of the refined assembly Sscrofa11.1 creates a

good opportunity to enrich our current knowledge on SLA and annotate a whole new

haplotype. We focused on a genomic region spanning 2.7 megabases from MOG gene,

upstream from the class I sub-region (7:22,595,565), to RING 1, downstream to the class II

sub-region (7:25,256,223). This SLA region is well-assembled, even if the duplication of

polymorphic genes in some sub-regions can locally increase the difficulty of the assembly

and annotation process. The automated annotations from Ensembl and NCBI of the class I

genes are incomplete and even misleading in these highly duplicated subregions.

Particularly, a cluster of eight related SLA class I genes and pseudogenes (SLA-1,-5,-9,-3,-

2,-4 and two additional copies) within a 150kb region led to chimeric mapping of cDNAs and

further incorrect annotation. Additional analyses are required to clarify if the chimeric

mapping is due to errors in the assembly and/or to highly conserved duplicated segments. In

total, using a new PacBio long-read assembly and an Iso-seq-based annotation of nine

tissues, we have refined the annotation of 12 class I genes, 15 class II genes, and more than

120 other genes. The completed annotation update will be released in Ensembl.

P5

Genome-wide association study in newborn calf serum reveals QTL for natural antibodies in Swedish dairy cattle

J. Cordero-Solorzano 1,2, J.J. Wensman 1, M. Tråvén 1, J.A.J. Arts 2, H.K. Parmentier 2, H. Bovenhuis 2 & D.J. de Koning 1

1 Swedish University of Agricultural Sciences, Uppsala, Sweden 2 Wageningen University & Research, Wageningen, the Netherlands

Failure of passive transfer (FPT) occurs when a newborn calf does not absorb enough

antibodies (<10 g/l of IgG) from the colostrum. Some calves absorb antibodies very

effectively while others do not. This difference in uptake cannot be explained solely by the

time, amount and quality of the colostrum given. Natural antibodies (NAb) are produced

without any antigenic stimulation and target self-antigens and pathogen-associated

molecular patterns (PAMPs). Our objective was to estimate genetic parameters and detect

quantitative trait loci (QTL) for three NAb isotypes (IgG, IgM and IgA) in newborn calf serum

binding keyhole limpet hemocyanin (KLH) and muramyl dipeptide (MDP). Two experimental

farms were included in the study. Serum samples were collected from 831 calves between 2

to 7 days old, born from January 2015 to April 2017. 70% of the animals were Swedish Red

and 30% Swedish Holstein. Antibodies were measured from serum using indirect ELISAs.

To estimate genetic parameters, a linear mixed model was run, correcting for antibody

concentration of colostrum given, volume of first meal, time of birth to blood sampling time,

weight at birth and breed, including genetic effect, maternal effect and Herd-Year-Season of

calving with sample storage plate as random effects. An imputed 50K SNP array from a LD

7K array was used for the Genome-wide association study (GWAS), running the same

model but including the SNP genotype as a fixed effect. Heritabilities for NAb isotypes in

newborn calf serum ranged from 0.20 to 0.53, with a maternal effect ranging from 5 to 30%.

Genetic correlations between IgM and IgA ranged from 0.74 to 0.94. The GWAS revealed

one QTL on BTA1 for MDP-IgG, comprised of 3 SNPs (-log10(p) = 5.9), one significant and

two suggestive, ranging from 1-8 Mbp and another QTL on BTA3 for IgM (KLH and MDP)

consisting of 2 suggestive SNPs (-log10(p) = 5.02), from 13-25 Mbp. Our results suggest

that natural antibodies can potentially provide an effective tool to reduce FPT using genetic

selection.

P6

Genome-wide associations and fine mapping of immune traits in two dam lines using sequence data

Christina M. Dauben, Esther M. Heuß¹, Maren J. Pröll-Cornelissen¹, Katharina Roth¹, Hubert Henne², Anne K. Appel², Karl Schellander¹, Ernst Tholen¹, Christine Große-Brinkhaus¹

¹Institute of Animal Science, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany ²BHZP GmbH, An der Wassermühle 8, 21368 Dahlenburg-Ellringen, Germany

Health and immune traits are linked to robustness of piglets. To prevent performance

reduction through health impairment, it could be useful to enhance robustness due to

immune competence. Indicators triggering a health-promoting immune competence need to

be specified regarding negative impacts and interactions. However, the genetic background

of the porcine immune system still remains unclear. So far, a limited number of immune

relevant QTL has been analyzed. Therefore, this study aims to identify biological relevant

SNPs associated with health and immune traits in pigs.

A total of 535 Landrace (LR) and 461 Large White (LW) piglets were included in this study.

Phenotypes were recorded for the complete and differential blood count as well as for

cytokines and haptoglobin, resulting in 20 complex immune traits. All animals were

genotyped by using the Illumina PorcineSNP60 BeadChip. Based on genotype and pedigree

information, a subset of 57 animals, which present the genetic structure of the populations,

was selected for whole genome sequencing. Afterwards, a breed-specific GWAS was

performed with a generalized linear model. Using sequence data for fine mapping, significant

QTL regions associated with immune regulative mechanisms are analyzed in more detail.

In total, the univariate GWAS revealed 355 significant SNPs in LR and 96 significant SNPs

in LW. Numbers and positions of the SNPs vary between the traits and breeds. However,

across both breeds, we identified a region on SSC9 associated with IL1β, IL4, IL6, IL10 and

TNFα, suggesting pleiotropic effects. First results of the fine mapping show 15 variants

located close to a specific SNP within this region. All of the variants occure in LR and LW,

indicating an across-breed effect on cytokines mediating in the immune response. Moreover,

a region on SSC12, associated with neutrophils, monocytes and erythrocytes, is detected in

both breeds. This region includes PIK3R5 as a candidate gene affecting hemostasis through

platelet activation.

In conclusion, along with the knowledge about the genetic potential of the traits analyzed, we

are able to clarify mechanisms interacting in the porcine immune system. This information

may be used to improve breeding strategies and thereby enhancing robustness of piglets.

P7

Identifying the Genetic Regions Associated with Bovine Monocyte-Derived Macrophage Nitric Oxide Production: A Cellular Genome-Wide Association Study

Mehdi Emam1,2,4, Saeid Tabatabaei1, Mehdi Sargolzaei3, Saeid Khosravani4, Flavio Schenkel2, Bonnie Mallard1,2

1- Department of Pathobiology, Ontario Veterinary College, University of Guelph 2- Center for Genetic Improvement of Livestock, Dep. of Animal Biosciences, University of Guelph 3- Select Sires, Inc., Plain City, OH, USA 4- Biomics Analytica Inc., Guelph, ON, Canada

Macrophages are at the cornerstone of the innate immune systems. These cells are among

the first responders to infections with a notable role in eliminating the pathogens via

phagocytosis and producing microbicidal components such as nitric oxide (NO-). Recently,

we have shown that the variation in the magnitude of in vitro NO- response is significantly

correlated with the phagocytic ability of bovine Monocyte-Derived Macrophages (MDM) in

response to Escherichia coli (E. coli) (p-value: 0.01, ρ: 0.62) and Staphylococcus aureus (p-

value: <0.01, ρ: 0.70). Moreover, the variation in NO- response to E. coli in a highly

controlled in vitro system was largely determined by the host genetics (pedigree-based

heritability of 0.99 with the standard error of 0.05 and permutation p-value of 0.007 in 1,000

iterations). To identify the genetic regions that associate with NO- response to E. coli, 58

samples were collected from healthy dairy Holsteins. The concentration of nitrites and

nitrates in the MDM culture supernatant was measured by Griess Assay 48 hours after

treatment with E. coli. All cows were genotyped by ZM2 chip, and 43,471 SNPs passed the

quality controls (excluding X chromosome). The numerical regression method followed by

permutation (10,000 iterations) was used to identify SNPs that are associated with NO-

response of MDMs against E. coli. The significant SNPs were used to train a neural network

(NN) algorithm, a deep learning method, to test the accuracy of genomic prediction. The

dataset was divided into 70% training, 15% validation and 15% test to predict the phenotype

of NO- response in 3 classes of high, average and low. The association study showed that

eight SNPs on chromosomes 4, 5, 6, 19, and 27 are significantly associated with nitric oxide

response of MDMs. These SNPs described 78% of the phenotypic variation. The narrow

sense heritability was estimated to be 0.46. The NN predicted the phenotypic class of 46 out

of 58 samples correctly (79% success rate). Overall, this study has revealed several genetic

regions that control NO-, one of the important functions of bovine macrophages. In addition,

the NN that was trained in this study could be used to predict the macrophage NO- response

to E. coli in association with clinical mastitis records in a larger independent sample

population of Holsteins.

P8

FORTIOR Genetics, a platform to enhance disease resistance by genetic selection in aquaculture

Yoannah FRANCOIS 1,3, Joëlle CABON 3, Thierry MORIN 3, Daniel GUEMENE 2, Pierrick HAFFRAY 1

1 Syndicat des Sélectionneurs Avicoles et Aquacoles Français (SYSAAF), Rennes, France. 2 Syndicat des Sélectionneurs Avicoles et Aquacoles Français (SYSAAF), Nouzilly, France. 3 French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Ploufragan-Plouzané-Niort Laboratory, Viral Fish Pathology Unit, Plouzané, France.

The FORTIOR Genetics platform was created to mutualize skills (genetic and infectiology)

and resources of both SYSAAF and ANSES for the benefit of the health of farmed fish and

the French fish farming industry. Its aim is to propose controlled infectious challenges on

siblings for several serious diseases in partnership with breeding companies. This platform

contributes to a sustainable approach aiming at reducing inputs in aquaculture, reducing

resistance to antibiotics and increasing sanitary fish qualities. ANSES facilities are EU

approved for fish experimentations and are adapted for infectious challenges of genetic

purpose on large amount of juveniles (from 1000 to 2000) of different sizes. Major

parameters such as the type of water (fresh or salted), the temperature, the debit, the tanks

size, can be adjusted. Several infectious challenges were held since the beginning of RE-

SIST program on different host/pathogens couple such as sea bass/Viral Nervous Necrosis,

sea bass/vibriosis or sea bream/photobacteriosis. They are used to estimate genetic

breeding values of candidates to several different traits as well as the genetic parameters

(heritability, genetic correlations with growth and production traits). For example, heritabilities

of resistance to nodavirosis and vibriosis were estimated at 0.11 ± 0.05 and 0.08 ± 0.03

respectively with a negative correlation of -0.45 ± 0.17 between both traits. Sea bream

resistance to photobacteriosis heritability was estimated at 0.24 ± 0.07, with a strong genetic

correlation with commercial weight (0.75 ± 0.10) but a low correlation with carcass yield (-

0.20± 0.13).

FORTIOR Genetics is one of the first European tool for phenotyping farmed fish to different

disease resistances in order to support domestication and genomic selection developed by

breeders. Several improvement were identified to standardize infectious challenges and

make them as representative as possible of the field conditions. Redefining the studied

phenotypes and test new genomics tools could also help to improve the efficiency and

relevance of FORTIOR Genetics results, and contribute to the generation of knowledge on

fish disease resistance.

P9

Host-pathogen interactions: Understanding the bovine macrophage transcriptional response to Toxoplasma gondii

Gossner, A., Hassan, M.

The Roslin Institute & R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG. UK.

We aimed to unravel the functional diversity and coordinated response of bovine

macrophages to intracellular parasitic infection using dual RNA sequencing. How the host

immune cells respond to pathogens determines the outcome of an infection. Thus,

understanding how immune cells participate and respond to pathogen-related signals as well

as how the pathogen optimizes its virulence mechanisms in the variable intracellular

microenvironment, has the potential to reveal novel disease management strategies. In this

study we used Toxoplasma gondii, which the World Health Organization ranks 4th among

foodborne parasites with the greatest global impact, and bovine macrophages which are the

major immune cells that respond to Toxoplasma, to interrogate the transcriptional response

of livestock immune cells to intracellular pathogens. In this study we used Toxoplasma

gondii, which the World Health Organization ranks 4th among foodborne parasites with the

greatest global impact, and bovine macrophages which are the major immune cells that

respond to Toxoplasma, to interrogate the transcriptional response of livestock immune cells

to intracellular pathogens. We report that in the absence of a pre-stimulant, Toxoplasma

upregulates molecular pathways associated with macrophage phosphorylation and growth.

Immune signalling pathways in interferon gamma pre-stimulated macrophages replaced

these pathways. Insights from this study has the potential to expedite long-term efforts

towards exploiting the host's immune responses or targeting the pathogen's virulence

mechanisms as alternative approaches to controlling livestock infectious diseases, thereby

reducing our dependence on existing antimicrobials, and improving food safety.

P10

Genetics of pasteurellosis resistance in rabbits

Gunia M., Shrestha M.1, Bed’hom B.2, David I.1, Guitton E.3, Helies V.4 ,Helloin E.5, Herbert C.6, Maupin M.7, Lantier F.5, Garreau H.1

1GenPhySE, INRA, INPT, ENVT, Université de Toulouse, 31326 Castanet-Tolosan, France 2GABI, INRA, AgroParisTech, Université Paris-Saclay, 78352 Jouy-en-Josas, France 3PECTOUL, INRA, 31326 Castanet-Tolosan, France 4PFIE, INRA, 37380 Nouzilly, France 5ISP, INRA, Université François Rabelais de Tours, UMR 1282, 37380 Nouzilly, France 6HYCOLE, Route de Villers-Plouich, 59159 Marcoing, France 7HYPHARM SAS, La Corbière, Roussay, 49450 Sèvremoine, France

Pasteurellosis is the first cause of rabbit culling in commercial herds. Antibiotic treatments

against pasteurellosis have a low efficiency and may lead to the development of antibiotic

resistance. Breeding rabbits for their resistance to this disease could be a way to tackle this

issue. For this purpose, 964 crossbred rabbits were inoculated with a strain of Pasteurella

multocida and monitored during 14 days. Body weight, body temperature, abscess

dissemination, blood cell count, and bacterial count were registered on the inoculated

rabbits. A resistance score was created combining the survival of the animal (alive or dead

at Day 14) and the abscess and bacterial dissemination scores. Two traits under selection,

litter size and weaning weight, were also recorded in the selection farms on the purebred

rabbits used to produce the experimental population. Genetic parameters analyses were

carried out using linear animal models. Disease response was very variable with 7% of

resistant rabbits and 11% of highly susceptible rabbits. The heritabilities of the resistance,

bacterial dissemination, and abscess dissemination scores ranged from 0.09±0.05 to

0.16±0.06. Due to the relatively low number of inoculated animals, the genetic correlations

could not be estimated with a high accuracy. The genetic correlation between the resistance

score and the litter size seems to be unfavorable. On the opposite, the genetic correlations

between the resistance score and growth traits seems to be favorable. According to these

results, selection on pasteurellosis resistance seems to be feasible.

P11

The European Variation Archive: Genetic variation archiving and accessioning for all species

Baron Koylass, Cristina Yenyxe Gonzalez, Jose Miguel Mut Lopez, Sundararaman Venkataraman, Andres Silva, Thomas Keane

EMBL-European Bioinformatics Institute, Cambridge, United Kingdom

Introduction: The European Variation Archive (EVA, https://www.ebi.ac.uk/eva) is a primary

open repository for archiving, accessioning, and distributing genome variation including

single nucleotide variants, short insertions and deletions, and larger structural variants in any

species.

Materials and Methods: Since launching in 2014, the EVA peers with NCBI-based database

dbSNP to form a worldwide network for exchanging and brokering of variation data. From

2017, issuing and maintaining variant accessions is divided by species: the EVA is

responsible for non-human species and dbSNP for human. Other services include standard

variant annotation, calculation of population statistics, and an intuitive browser to view and

download queried variants in either Variant Call Format (VCF) or Comma-Separated Value

(CSV) files. In addition, a comprehensive REST-API is available to query/export data that

supports the htsget streaming protocol defined by the Global Alliance for Genomics and

Health (GA4GH). The EVA also contributes to maintaining the VCF, implementing a

validation suite (https://github.com/ebivariation) to ensure correctness of all the submissions

made to the archive.

Results: The EVA has archived more than 770 million unique variants across 546 studies

and 51 species. 280 million identifiers have also been imported from dbSNP, and 330 million

new identifiers have been issued. The API is also species-agnostic and is extensively used

by translational resources including Ensembl, Ensembl Genomes, Open Targets, WheatIS

and the 1000 Sheep Genomes Project.

Conclusion: A key function of the EVA as a long term data archive is to provide standardised

stable identifiers so that studies and discovered variants can be referenced in publications,

cross-linked between databases, and integrated with successive reference genome builds.

With these goals, the EVA will continue to act as a primary repository for variation data from

any species.

P12

Aetiopathogenesis and genomic architecture of resistance to lameness in dairy cattle

Androniki Psifidi1, Georgios Oikonomou2, Stuart Carter2, Dong Xia1, Dirk Werling1, Mike Coffey3, Georgios Banos3

1 Royal Veterinary College, University of London, Hatfield, UK 2 Institute of Veterinary Science, University of Liverpool, UK 3 Scotland’s Rural College, Edinburgh, EH25 9RG, UK

Maintaining good foot health is one of the most critical challenges the dairy cattle industry

faces today. This is because poor foot health leads to reduced mobility of the animal and

causes lameness. The latter is a debilitating and painful condition, which is described as one

of the clearest indicators of compromised welfare in dairy cattle and one of the most

important factors for the involuntary replacement of animals. Claw horn disruption lesions

(CHDL) such as sole haemorrhages, sole ulcers and white line disease are the most

prevalent conditions associated with impaired mobility and pain in dairy cattle in the UK and

worldwide. In a recent study by our group, 44% of cows developed CHDL during 12 months

of monitoring (26%, 12% and 19% for sole haemorrhages, sole ulcers and white line

disease, respectively). Despite the importance of CHDL, the reasons leading to their

development have not yet been fully described. There are also genetic differences between

individual animal susceptibility to CHDL development; we have already estimated a

heritability of 0.29+0.11 for sole ulcers, and identified single nucleotide polymorphisms

located on chromosome 25 accounting for 21% of the total genetic variance. Moreover, the

anatomic structure of the foot, animal hormonal and immune profiles, inflammation around

calving, animal metabolism, and management practices have been thought to contribute.

Currently, we have a new project to study all these factors together using a large number of

animals (3,000 Holstein cows) raised in four UK commercial farms. Animals recruited for this

project are pregnant cows, which are closely monitored by a qualified veterinarian from 60

days before calving through to the first half of the ensuing lactation. Systematic recording of

CHDL, the thickness of the digital cushion (a protective anatomical structure of the foot),

hormonal levels in blood, specific proteins in blood and tissues indicative of inflammation,

acid levels in blood indicative of altered metabolism, and cow activity and resting patterns

are taking place, generating a unique database of relevant information. Individual cattle

genomic profiles will be analysed then together with cow measurements to assess the

environmental and genetic impact on CHDL. Outcomes of this project may improve

considerably animal health and welfare by underpinning the development of efficient

management practices, new breeding tools and novel pharmaceutical interventions.

P13

Genetic background of brachycephalic obstructive airway syndrome in the pug, French bulldog and bulldog.

Lajos Kalmar1, Nai-Chieh Liu1, Eileen Troconis1, Hattie Wright1, Cathryn Mellersh2, Jane Ladlow1, David R. Sargan1

1. Department of Veterinary Medicine, University of Cambridge, 2. Animal Health Trust, Newmarket,

Introduction: Brachycephalic obstructive airway syndrome (BOAS) is a respiratory disease of

short headed dogs. About 50% of extreme brachycephalic dogs over three years old show

noisy and laboured breathing, with exercise intolerance, heat intolerance, sleep apnoea,

regurgitation and in the worst cases cyanosis, collapse and death. Within each breed BOAS

shows a wide range in severity from good health with totally clear airways to life threatening

cases.

Objective: The aim of the study was to find candidate genetic regions associated with BOAS.

Materials & Methods: DNA was collected from unaffected and affected dogs from 3 breeds

(pug, French bulldog (FB) and bulldog (BD)) in the UK. Standardised exercise tolerance

based clinical assessments were used to assign dogs to four BOAS severity classes,

Genome-wide association studies used the Illumina CanineHD SNP array and 152 pugs,

191FB and 108 BD . pLink and Emmax software were used to find candidate loci and GCTA

software to calculate heritability, estimated breeding value and predictive force. Two control

and two affected dog genomes of each breed were sequenced.

Results: In each breed, selective sweeps occurred around several loci already identified as

conferring the brachycephalic skull shape. Estimated narrow-sense heritability for BOAS

varied between 37% and 60%. After removal of covariants genome wide significance was

reached by only one locus in each breed, but nominal significance (upward deviation from

the 95% CI of the Q/Q plot) was reached by 7 additional loci per breed, suggesting a

polygenic trait. Only limited overlaps exist between candidate regions in different breeds.

Further loci close to this limit were also included in iterative locus optimisation combined with

Monte-Carlo cross validation to define sets of 8-11 discrete loci per breed that together

account for >33% of total phenotypic variance in each breed. Linear models based on the

selected loci predict severe BOAS cases with very high probability (AUC >90%) in each

breed. Implicated loci include genes previously implicated in human head shape

abnormalities and are enriched for genes with ontologies related to cartilage and skeletal

development. However, no unambigous causal variants in these genes were found.

A second cohort study is now underway. This will allow development of an effective genetic

diagnostic pipeline for breeders to reduce the prevalence of BOAS, using a genomic

breeding value approach.

P14

Survival of Pigs Classified by Immune Response Phenotype using the HIR™ Technology when Naturally Challenged with Common Swine Pathogens

Julie Schmied1, Austin Putz2, Jack Dekkers2, Michael Dyck3, Frederic Fortin4, John Harding5, Graham Plastow3, PigGen Canada6, Bonnie Mallard1

1 Ontario Veterinary College, University of Guelph,Guelph, Canada 2 Iowa State University, Ames, USA 3 University of Alberta, Edmonton, Canada 4Centre de Développement du Porc du Québec, Québec City, Canada 5University of Saskatchewan, Saskatoon, Canada 6PigGen Canada, Guelph, Canada

Managing disease in pork populations is one of the most costly and difficult challenges for

pork producers. The High Immune Response (HIR™) Technology developed at the

University of Guelph was first successfully tested in pigs and allows for the identification of

animals with more robust and balanced immune responses (IR). It's now used commercially

to identify dairy cattle with increased capacity for antibody and cell mediated-IR (AMIR,

CMIR), and subsequently increased disease resistance. Previously, when Yorkshire pigs

were selectively bred for IR it was found that high (H) IR pigs had improved responses to

vaccination and pathogen challenge compared to the control line and low (L) responders.

Although previous research in pigs demonstrated favourable responses to breeding pigs for

HIR, the method has not been tested in commercial herds. Here, differences in mortality rate

and likelihood of survival of 1915 Yorkshire x Landrace F1 barrows, IR phenotyped for both

AMIR and CMIR, were examined. It was hypothesized that when naturally exposed to

common swine pathogens, a higher proportion of pigs classified as H-immune responders

would survive disease challenge and be more likely to reach slaughter than pigs classified

as average and low immune responders. Results indicate, pigs of H-IR and mixed-H

phenotypes died less frequently than those with average or L-IR (p=0.0015). Moreover, high

AMIR pigs died less frequently than those with an average or low AMIR (p=0.0402). Analysis

of survival curves revealed a positive association between likelihood of death and

phenotype, (p=0.0012) such that, pigs classified as L and A immune responders were more

likely to die before reaching slaughter, than pigs classified as having a mixed-H or H-IR.

Therefore, IR phenotyping of pigs clearly identifies animals with the potential to withstand

pathogen-challenge by making strong and appropriate IRs. These animals may also display

production related advantages, as observed in previous experiments. Therefore, the

integration of the HIR™ technology into commercial pig breeding programs is expected to

yield both health and production benefits.

P15

A Matter of Life and Death: determining genomic factors responsible for resistance to Highly Pathogenic Avian Influenza

Jacqueline Smith, Cal Donnelly1, Wioleta Drobik-Czwarno2, Anna Wolc3,4, Janet E. Fulton3, Paul Digard1

1 – The Roslin Institute, Easter Bush Campus, Midlothian, EH25 9RG, UK 2 – Warsaw University of Life Sciences, 02-787 Warszawa, Poland 3 - Hy-Line International, Iowa, IA 50266, USA 4 - Iowa State University Ames, Iowa 50011-3150, USA

DNA samples collected from survivors of recent outbreaks of highly pathogenic avian

influenza (HPAI) in Mexico and the USA (showing >99% mortality) have provided a rare and

unique opportunity to study the genetic mechanisms underpinning resistance of chickens to

this devastating and economically important disease. Comparing whole-genome sequence

(WGS) data of survivors with that from age-matched controls, has allowed us to perform

genome-wide association studies (GWAS) to elucidate quantitative trait loci regions (QTLRs)

that contain genes regulating the survival phenotype. Subsequent annotation of the QTLRs

has identified coding and non-coding RNAs that may be contributing to resistance

mechanisms. The presence of single nucleotide polymorphisms (SNPs) has been confirmed

within sequences and predicted functional effects determined. Candidate genes for HPAI

resistance are prioritized based on GWAS significance, presence of deleterious SNPs,

known biology and differential expression in existing data sets from other avian flu

transcriptomic projects. Candidate genes and mutations thought to be involved in resistance

will be functionally tested in vitro to observe their effects on viral replication and cellular

response to infection. An understanding of the genetics underlying HPAI resistance in

chickens will enable progress toward controlling avian influenza, whether through selective

breeding strategies, improved vaccine design or providing targets for genome editing.

Mitigating the effects of HPAI will have implications for both the poultry industry and for

public health.

P16

ZBED6 Knock-out in pig leads to the hypertrophy in skeletal muscle

Dandan Wang, Xiangyang Xing, Yuting Tang, Yuehui Ma, Dengke Pan, Lin Jiang

Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China

Introduction

A single nucleotide substitution in intron 3 of insulin-like growth factor 2 (IGF2) abrogates in

vitro interaction with ZBED6, leading to the high expression of IGF2 and increased lean meat

in domestic pigs. Here, we investigated the mechanism underlying ZBED6 in growth of

skeletal muscle using Zinc finger, BED-type containing 6 (ZBED6) knock-out (ZBED6−/−)

Bama pigs.

Method

Using CRISPR-Cas9, we obtained five ZBED6−/− founder female pigs with one-base pair

deletion (-1bp/-1bp) leading to short truncated protein. Afterwards mating leads to three

ZBED6+/- F1 male piglets and five wild type female pigs with the same birth date were used

as wild type. Each individual pig was measured for the blood test monthly. Three of each

group ( ZBED6−/−, ZBED6+/- and WT) were slaughtered for the meat production

performance and seven tissue samples (heart, gastrocnemius muscle, longissimus dorsi,

liver, spleen, lung and kidney) were collected for expression analysis and transcriptome

analysis.

Results and Discussion

These transgenic pigs showed markedly increased lean mass and lean mass rate, increased

muscle fiber diameter and larger internal organs (heart, liver and spleen). The striking

phenotypic changes of ZBED6−/− pigs were in agreement with the remarkable up-regulation

IGF2 expression in serum concentrations, mRNA and protein in multiple tissues (heart,

gastrocnemius muscle, longissimus dorsi, spleen, lung and kidney) except liver. But bigger

size and tiny changes of IGF2 in liver indicated ZBED6 has other target genes.

Transcriptome analysis of muscle tissues (cardiac muscle, gastrocnemius muscle and

longissimus dorsi), liver, spleen, lung and kidney, identified differential expression of genes

(DEGs) associated with skeletal muscle development, and immune category. CDKN1A was

identified as a putative direct target gene of ZBED6 for regulating growth of muscle and

internal organs, in addition to IGF2. ZBED6 may influence immune system by regulating

ISG15 expression.

Keywords: Pig CRISPR-Cas9 Transcriptome Analysis Muscle

P17

ChHIB Promotes Ubiquitination and Degradation of MyD88 to Suppress Innate Immune response

Fei Wang, Qinghe Li, Qiao Wang, Ranran Liu, Maiqing Zheng, Huanxian Cui, Jie Wen and Guiping Zhao

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, China

Uncontrolled immune responses to bacterial infection have been shown to induce

pathological damage. Homeostasis regulation of immune responses to bacteria is critical for

avoiding excessive production of proinflammatory cytokines and type I interferon. Here, we

report that the E3 ubiquitin ligase ,ChHIB, was induced by bacterial

lipopolysaccharides(LPS) infection in chicken macrophage cell line HD11. Knockdown of

ChHIB augmented the interleukin-1β and interleukin-8 response to LPS. Biochemical

analyses showed that ChHIB interacted with the central adaptor MyD88, which converts the

signal from toll-like receptors to activate following pathways. Overexpression of ChHIB

promoted the degradation of MyD88 via K48-linked ubiquitination at Lys118, Lys 124 and

Lys 143 through a proteasome-dependent pathway. These findings indicate that E3 ligase

ChHIB is an important negative-feedback regulator of innate immune responses to bacterial

lipopolysaccharides by targeting MyD88.

P18

Eradication of infectious disease in farm animals through gene editing: a theoretical feasibility study

Andrea Doeschl-Wilson 1, Jaap Buntjer1, Bruce Whitelaw1, Fiona Hely2, Gertje Petersen2, Peter Amer2, Tim Byrne3

1: The Roslin Institute, The University of Edinburgh, UK. 2: AbacusBio, Dunedin, NZ 3: AbacusBio, Edinburgh, UK

Novel genomic technologies such as gene editing offer exciting new opportunities for

infectious disease control, especially in situations where conventional approaches have

failed. Recent breakthroughs in gene editing of pigs, in which a simple disruption of the

CD163 gene confers complete resistance to infection with the Porcine Reproductive and

Respiratory Syndrome Virus (PRRSV), exemplify this opportunity. Despite huge global

efforts, PRRS continues to persist and remains one of the costliest infectious disease for the

pig industry worldwide. Compared to all existing control methods, gene editing is the only

method known to date that can fully protect pigs from becoming infected with PRRSV and

thus also from transmitting the disease. This raises the question as to how the introduction of

gene edited pigs in national pig herds would reduce PRRS prevalence, and in particular,

whether the dispersion of gene edited pigs in commercial pig herds could eventually help to

eradicate this devastating disease on a national level.

A genetic-epidemiological model was developed to predict the risk of PRRS outbreaks in

national pig herds. Herds were assumed to differ in size, the proportion of edited pigs as well

as in PRRS exposure probability. The model predicts how the total number of gene edited

pigs in the national population, and their distribution across herds, affects PRRS prevalence.

Based on these model predictions it was possible to determine the proportion of gene edited

pigs and the proportion of herds adopting gene editing required to eradicate PRRS. The

results suggest that PRRS eradication through gene editing alone would be extremely

difficult as it would require large proportions of gene edited pigs. In contrast, when used

complemented by conventional control option such as vaccination, introduction of gene

edited pigs into commercial pig populations could achieve the hitherto unprecedented

opportunity of PRRS eradiation on a national scale. The results of this proof of concept

modelling study provide some first insights for all stakeholders into the potential benefits,

feasibility and cost-effectiveness of gene editing as disease control strategy in domestic

livestock, and may contribute towards public acceptance of these highly contested

innovative technologies.

P19

Genomic, transcriptomic, and epigenomic features differentiate genes that are relevant for muscular polyunsaturated fatty acids in the common carp

Jian Xu, Hanyuan Zhang, Yanliang Jiang, Zixia Zhao, Ruyu Tai

Chinese Academy of Fishery Sciences, Beijing 100141, China

Polyunsaturated fatty acids (PUFAs) are a set of important nutrients that mainly include

arachidonic acid (ARA4), docosahexenoic acid (DHA), eicosapentaenoic acid (EPA), and α-

linolenic acid (ALA). Recently, fish-derived PUFAs have been associated with cardiovascular

health, fetal development, and improvement of brain functions. Studies have shown that fish

muscular tissues are rich in PUFAs, which are influenced by various factors, including

genetic variations, regulatory profiles, and methylation status of desaturase genes during

fatty acid desaturation and elongation processes. However, the genetic mechanism and the

pathways involved in fatty acid metabolism in fishes remain unclear. We conducted GWAS

using a 250K SNP array in a population of 203 samples of common carp (Cyprinus carpio)

and identified 15 genes associated with muscular PUFA content. Then, RNA-Seq and whole

genome bisulfite sequencing (WGBS) of different groups with high and low EPA, DHA,

ARA4, and ALA contents in muscle, liver and brain tissues were conducted, resulting in

6,750 differentially expressed genes and 5,631 genes with differentially methylated

promoters. Gene ontology and KEGG pathway enrichment analyses of RNA-Seq and WGBS

results identified enriched pathways for fatty acid metabolism, which included the

adipocytokine signaling pathway, arachidonic acid and linoleic acid metabolism pathway,

and insulin signaling pathway. Integrated analysis indicated significant correlations between

gene expression and methylation status among groups with high and low PUFA contents in

muscular tissues. Taken together, these multi-level results uncovered candidate genes and

pathways that are associated with fatty acid metabolism and paved the way for further

genomic selection for PUFA traits.

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Notes

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Notes

Delegate List

Pier Luigi Acutis

Istituto Zooprofilattico Piemonte

pierluigi.acutis@izsto.it

Leif Andersson

Uppsala University

leif.andersson@imbim.uu.se

Georgios Banos

Roslin Institute

georgios.banos@roslin.ed.ac.uk

Tom Berghof

Wageningen University & Research

tom.berghof@wur.nl

Piter Bijma

Wageningen University

piter.bijma@wur.nl

Joseph Bird

Anglia Ruskin University

joseph.bird@anglia.ac.uk

Fany Blanc

INRA

fany.blanc@inra.fr

Miguel Blanco Fuertes

IRTA-CReSA

miguel.blanco@irta.cat

Laura Buggiotti

Royal Veterinary College

lbuggiotti@rvc.ac.uk

Nina Burkhardt

LMU Munich

nina.burkhardt@lmu.de

Margarida Cardoso Moreira

University of Heidelberg

m.moreira@zmbh.uni-heidelberg.de

Mathieu Charles

INRA

mathieu.charles@inra.fr

Juan Cordero Solorzano

Swedish University of Agricultural

Sciences

juan.cordero@slu.se

Christina Dauben

University of Bonn

cdau@itw.uni-bonn.de

Lior David

Hebrew University of Jerusalem

lior.david@mail.huji.ac.il

Lydia de Haer

CRV

mia.oudenhoven@crv4all.com

Dirk Jan de Koning

Swedish University of Agricultural

Sciences

dj.de-koning@slu.se

Appolinaire Djikeng

University of Edinburgh

appolinaire.djikeng@ctlgh.org

Seyedmehdi Emam

University of Guelph

semam@uoguelph.ca

Tove Fall

Uppsala University

Tove.fall@medsci.uu.se

Mark Fife

The Pirbright Institute

mark.fife@pirbright.ac.uk

Yoannah Francois

SYSAAF

yoannah.francois@anses.fr

Moran Gershoni

Volcani Institute

moran.gershoni@weizmann.ac.il

Anton Gossner

Univeristy of Edinburgh

a.gossner@ed.ac.uk

Melanie Gunia

INRA

melanie.gunia@inra.fr

John Hammond

The Pirbright Institute

john.hammond@pirbright.ac.uk

Terhi IsoTouru

Luke Finland

terhi.iso-touru@luke.fi

Lucia Kaal

Wageningen University & Research

lucia.kaal@wur.nl

Jim Kaufman

University of Cambridge

jfk31@cam.ac.uk

Julian Knight

University of Oxford

julian@well.ox.ac.uk

Baron Koylass

EMBL-EBI

baron.koylass@ebi.ac.uk

Susan Lamont

Iowa State University

sjlamont@iastate.edu

Kyusang Lim

Iowa State University

kyusang@iastate.edu

Joan Lunney

USDA ARS BARC

joan.lunney@ars.usda.gov

Bonnie Mallard

University of Guelph

bmallard@uoguelph.ca

Alison Mather

Quadram Institute Bioscience

alison.mather@quadram.ac.uk

Melissa Monson

Iowa State University

msmonson@iastate.edu

Massimo Palmarini

University of Glasgow

massimo.palmarini@glasgow.ac.uk

Christopher Payne

University of Stirling

c.j.payne1@stir.ac.uk

Chris Pooley

The Roslin Institute

christopher.pooley@roslin.ed.ac.uk

Androniki Psifidi

The Royal Veterinary College

apsifidi@rvc.ac.uk

Eleanor Raffan

University of Cambridge

er311@cam.ac.uk

Douglas Rhoads

University of Arkansas

drhoads@uark.edu

Joana Rodrigues

Anglia Ruskin University

joana.rodrigues1@anglia.ac.uk

Claire Rogel Gaillard

INRA

claire.rogel-gaillard@inra.fr

Linda Saif

The Ohio State University

saif.2@osu.edu

Helen Sang

University of Edinburgh

helen.sang@roslin.ed.ac.uk

David Sargan

University of Cambridge

drs20@cam.ac.uk

Carl Schmidt

University of Delaware

schmidtc@udel.edu

Julie Schmied

University of Guelph

jschmied@uoguelph.ca

Holly Shelton

The Pirbright Insitute

holly.shelton@pirbright.ac.uk

Masoud Shirali

AFBI

masoud.shirali@afbini.gov.uk

Jacqueline Smith

Roslin Institute, University of Edinburgh

jacqueline.smith@roslin.ed.ac.uk

Anna Sonesson

Nofima

anna.sonesson@nofima.no

Christi Swaggerty

USDA / ARS

christi.swaggerty@ars.usda.gov

Christine Tait Burkard

University of Edinburgh

christine.burkard@roslin.ed.ac.uk

Spring Tan

University of Edinburgh

wtan2@exseed.ed.ac.uk

Christopher Tuggle

Iowa State University

cktuggle@iastate.edu

Lara Urban

EMBL-EBI

lurban@ebi.ac.uk

Caray Walker

Anglia Ruskin University

caray.walker@anglia.ac.uk

Dandan Wang

CAAS

wangdd1993@126.com

Fei Wang

Chinese Academy of Agricultural Sciences

feiwang2840@163.com

Ying Wang

University of California, Davis

ucywang@ucdavis.edu

David Williams

University of Cambridge

dlw33@cam.ac.uk

Andrea Wilson

Roslin Institute, University of Edinburgh

andrea.wilson@roslin.ed.ac.uk

Anna Wolc

Iowa State University

awolc@iastate.edu

Jian Xu

Chinese Academy of Fishery Sciences

xuj@cafs.ac.cn

Guiping Zhao

Chinese Academy of Agricultural Sciences

zhaoguiping@caas.cn

Huaijun Zhou

University of California, Davis

hzhou@ucdavis.edu

Index

Acutis, P L S39 Saif, L S1

Sargan, D P13

Berghof, T S9, P1 Schmied, J P14

Bijma, P S29 Shelton, H S53

Blanc, F S33 Smith, J P15

Blanco Fuertes, M P2 Sonesson, A S21

Buggiotti, L P3

Burkhardt, N S49 Tait-Burkard, C S11

Tan, S S15

Cardoso Moreira, M S45 Tuggle, C S43

Charles, M P4

Cordero Solorzano, J P5 Wang, D P16

Wang, F P17

Dauben, C P6 Wang, Y S25

David, L S47 Wilson, A P18

de Koning, D-J S19 Wolc, A S13

Emam, S P7 Xu, J P19

Fall, T S27 Zhao, G S41

Francois, Y P8 Zhou, H S35

Gossner, A P9

Gunia, M P10

Kaufman, J S5

Knight, J S59

Koylass, B P11

Lim, K-S S23

Lunney, J S3

Mallard, B S7

Mather, A S51

Monson, M S31

Palmarini, M S37

Payne, C S57

Pooley, C S17

Psifidi, A P12

Rhoads, D S55