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Australian Registered Cattle Breeders Association
Seminar proceedings
38th AGM
8th August 2012
“The MLA vision for genetics and genomics RDE post CRC”
Rob Banks
Aims
• Producers can make informed choices in buying bulls
• Double the rate of genetic progress (again)
• Breeders have skills, confidence and tools to drive genetic progress and bull sales
Where are we today?
• 25 years plus of BREEDPLAN and supporting R&D:– BLUP technology well‐established, proven and accessible
• 21 years of CRC R&D:– Genomic technology established and evolving fast
• Australian rate of genetic progress:– Average internationally– Heavily dependent on importation
Next 5 year RDE plan
• Maintain current levels of MLA RDE investment
• Coordination in national plan
• Increased focus on leading breeders and their programs
• Co‐investment models for hard‐to‐measure traits (building on BINs)
Next 5 year RDE plan
• Strategic R:– Methane and feed efficiency
– Improved genomic tools (cheaper)
– Use of genomic information underpinning within‐and across‐breed evaluations
Next 5 year RDE plan
• Applied R&D:– Drive polled gene testing
– Validation of CRC reproduction outcomes – incl. testing adaptiveness of high fertility
– Maintenance R&D (AGBU) tied to breed focus on genetic improvement and strong integration with SBTS/TBTS
• Breeding program design incl. use of genomics and international linkage
Next 5 year RDE plan
• Implementation:– Demonstration of value of improved fertility in north
– Supply chain integration to capture data from processor
– SBTS and TBTS more focussed on genetic gain in key studs/sources
– Capacity building (skills, knowledge, confidence) in breeders
challenges
• Basic technologies established and proven –focus is on more effective use
• Focus on role and effectivness of service providers
• Delivery model likely to evolve fast with genomics
• KPIs for BREEDPLAN and highlighting most effective studs
• RDE investment will be linked to outcomes –faster genetic progress
1
Genomic technologiesWhere to now?
The Age January 2011
2
Rare gene mutation could block Alzheimer's
Sydney Morning Herald 14 July 2012
The Sheep Industry
3
Breeding the mongrel that makes top dog worth top dollar
…..”Researchers will develop a breeding program after identifying DNA sequences associated with traits that make the best farm dogs”.
Sydney Morning Herald14 July 2012
What is DNA
4
Single Nucleotide Polymorphisms
Variation in DNA causes genetic variation in all species
Some traits are caused by single SNPs or deletions
ColourPollednessMyostatin mutationsGenetic diseases
5
Some traits are strongly influenced by a small number of genes
Effect of calpain and calpastatingenes on tenderness
Effect of myostatin mutations on muscling, fatness and retail beef yield
Most traits are influenced by many genes
GrowthFertilityMarblingFeed Efficiency
6
Sporting ability
Beef Cattle Genomics Research in Australia
Australian Cooperative Research Centre for Beef Cattle Genomic Technologies established in 2007
Goal was to discover 6 to 8 major genes for hard to measure traits
which would explain 50 percent of the genetic variation for each trait (accuracy of 70%)and would work across breeds.
7
One prominent CRC scientist said
Pedigree recording and performance recording would become irrelevant
Therefore Breed Societies and BREEDPLAN would not be needed in the future
CRC for Beef Cattle Genomics
Midway through the project the goal was reduced to explaining 15% of genetic variation (40% accuracy)
Using Genome Wide Scans with 10K then 50K and now 770K SNP tests
8
The same prominent scientist said
Genomic test results will be incorporated into EBVs to improve their accuracy
The tests will be most useful for hard to measure (eg tenderness) or expensive to measure traits (eg feed efficiency)
We can now measure up to 770,000 SNPs variations in DNA of in a single test
9
Models used to develop prediction equations
Large numbers of animals with accurate phenotypic measurements and SNP test results. (CRC model)
Large numbers of sires with high accuracy EBVs/EPDs with DNA SNP test results (Igenity and Merial models).
Independent populations used to “validate”the prediction equations (influential sires)
CRC used animals with phenotypic measurements
12,000 animals from the three CRCs
Angus progeny test (Trangie) 38 sires plus progeny
Shorthorn progeny test (Durham) 88 sires plus progeny
10
Which breeds?
Good numbers of Angus
Reasonable numbers of Shorthorn, Hereford, Brahman and Santa Gertrudisanimals in the calibration databases
Very few Charolais, Limousin or Murray Grey animals
Zero Simmental, Droughtmaster, Brangus , Red Angus, Gelbvieh, Blonde Aquitaine etc etc
Accuracy of CRC across breed Calibrations (released May 2012)
Feed Conversion Efficiency 0.44Fat Depth (p8 site) 0.27Tenderness 0.38Retail Beef Yield 0.13Marbling 0.30Eye Muscle Area 0.16Carcase Weight 0.30Hip Height 0.36Yearling Weight 0.36Age at puberty in females 0.28Post partum anoestrous interval 0.21Cow fertility when lactating 0.36Age at puberty in bulls 0.28Percent normal sperm 0.31
11
Within breed prediction equations calculated from CRC data
Trait Angus Limousin Hereford
Gestation Length 0.23 (0.06) 0.09 (0.08) 0.07 (0.13)
Birth weight 0.15 (0.05) 0.07 (0.07) 0.14 (0.07)
Weaning weight 0.13 (0.06) 0.02 (0.10) 0.16 (0.07)
600-Day weight 0.04 (0.06) -0.04 (0.08) 0.00 (0.08)
Scrotal circumference 0.01 (0.06) 0.04 (0.10) 0.02 (0.09)
Carcase P8 Fat 0.26 (0.16) 0.46 (0.14) -0.30 (0.37)
Carcase IMF 0.39 (0.11) -0.03 (0.25) 0.99 (0.57)
Days to Calving Age CL 0.14 (0.08) 0.35 (0.19) 0.21 (0.18)
Days to Calving PPAI 0.08 (0.13) 0.28 (0.20) -0.01 (0.20)
Net Feed Intake 0.11 (0.25) n.a. 0.00 (0.70)
Within breed calibrations calculated from CRC data
Trait Charolais Brahman
Gestation Length 0.00 (0.12) n.a.
Birth weight 0.25 (0.13) -0.77 (0.26)
Weaning weight 0.30 (0.12) 0.34 (0.10)
600-Day weight -0.17 (0.13) -0.10 (0.12)
Scrotal circumference 0.25 (0.12) 0.06 (0.14)
Carcase P8 Fat n.a. 0.66 (0.31)
Carcase IMF n.a. 0.55 (0.36)
Days to Calving Age CL n.a. 0.36 (0.14)
Days to Calving PPAI n.a. 0.27 (0.15)
Net Feed Intake n.a. n.a.
Shear Force n.a. 0.98 (0.18)
12
The pharmaceutical companies?
Pfizer and Merial (Igenity) established significant R & D teams with similar expectations as the CRC
Pfizer calibrationsUsed sires with high accuracy EBVs/EPDsand tested with 50K SNP test
Pfizer prediction equations developed for Australian Angus and incorporated into EBVs in March 2011 (accuracies ranged from 16% to 44%)
Cost of Pfizer test was initially $180 and is now around $85.
13
Merial calibrationsUsed sires with high accuracy EBVs/EPDsProvided Molecular Breeding Values based on a small number of SNPs(380) for some breeds. Have been validated/tested for Australian Angus and Limousin.
Angus genomic predictionsUSA USA Aust
Igenity1 Pfizer1 Pfizer1
Calving Ease Dir 0.47 0.33Birth Wt 0.57 0.51 0.40Weaning Wt 0.45 0.52 0.35Yearling Wt 0.34 0.64 0.41Feed Intake 0.45 0.65Scrotal 0.35 0.65 0.44Docility 0.29 0.60Mature Wt 0.53 0.58 0.29Carcase Wt 0.54 0.48 0.36Carcass Marb 0.65 0.57 0.20Carcass EMA 0.58 0.60 0.44Carcass Fat 0.50 0.56 0.45
Discovery size >5,0002 >5,0002 1,030
1 Trait definitions vary between calibrations2 Discovery and validation population combined
14
Angus genomic predictionsUSA USA Aust
Igenity1 Pfizer1 Pfizer1 Beef CRC1
Calving Ease Dir 0.47 0.33Birth Wt 0.57 0.51 0.40Weaning Wt 0.45 0.52 0.35Yearling Wt 0.34 0.64 0.41 0.36Feed Intake 0.45 0.65Scrotal 0.35 0.65 0.44Docility 0.29 0.60Mature Wt 0.53 0.58 0.29Carcase Wt 0.54 0.48 0.36Carcass Marb 0.65 0.57 0.20 0.30Carcass EMA 0.58 0.60 0.44Carcass Fat 0.50 0.56 0.45 0.27
Discovery size >5,0002 >5,0002 1,030 1,9143
1 Trait definitions vary between calibrations2 Discovery and validation population combined3 Across‐breed predictions based on 4,500 ‐ 10,000 animals
Where to now?
The Pfizer and Merial business models are not sustainable
Not a once only patented productOngoing R & D costs too high
Pfizer Animal Genetics division scaled down
Igenity sold by Merial to Neogen (who own the Geneseek genomics laboratory).
15
Where to now?The Information Nucleus projects which were intended to be validationdatabases have now become important discovery/calibrationdatabases
Birth DataGestation LengthCalving easeBirth weight
16
Growth Data
200 Day weight400 day weight600 day weight
Carcase DataCarcase weightEye Muscle AreaFat depth (rump and rib)Marbling score
17
Eating Quality
Shear Force (tenderness)Ultimate pHIntramuscular fat percentageOverall MSA eating quality
Other measurementsFeed EfficiencyMethane Emission??
18
The future
Breed Societies and BREEDPLAN are still alive and well
They will need to make decisions about how they use genomics technology in the future
The future
SNP technology improving rapidly and reducing in price
There is likely to be a new model for the calibration of genomics tests into EBVs
19
GeneseekGenomics Profiler 10K chip
Geneseek Genomic Profiler8500 selected SNPs which can be imputed to 50K
Approx 400 SNPs to enable conversion of ISAG microsatellite DNA types for parentage qualification??
Disease and trait markers
20
Geneseek Genomic ProfilerSNP based parentageHorn/poll Black/red colourGenetic defects Myostatin mutations Calpain (tenderness)Production trait predictionsBase cost approx $40
Current Expenditure by Australian Limousin breeders on DNA tests
DNA types/parent verification (400)Horn/poll (250)Colour (100)F94L myostatin (200)Other myostatin mutations (10)Protoporphyria (genetic defect) (50)
Total spend approx $25,000 pa (1000)
21
The future
Hope to get SNP data for production traits from GGP as a byproduct of testing for parentage, horn/poll, colour, myostatin, genetic diseases.
The future
The number of animals on breed society databases with genotypes (10K ) plus phenotypic and reasonably accuracy EBVs will increase.
We need to store full 10K or 50K or 700K results (not MBVs)
22
The new model
Continuous addition of 10K SNP test results to breed Association databases
10K tests will be imputed to 50K or 700K test results
Regular recalibration of SNP results for each breed. (no need to validate)
SummaryProgress has been slower than anticipated
The capability of DNA tests is increasing rapidly
The cost of DNA testing is decreasing
The need to continue to collect accurate measurements on as many traits for as many animals as possible is paramount
This technology is not going to disappear
23
Decisions decisions!Do we incorporate low accuracy CRC and/or Igenity calibrations into our EBVs?
Will we move to SNP based parentage?
Will Igenity or Uni of Qld offer cost effective packages using the Geneseek Genetics Profiler?
Are we going to start storing full SNP results on our database?
Do we extend current Information Nucleus projects?
1
Bovine Johnes Disease
I represent ARCBA on the National Johnes Disease Market Assurance
Reference Group
BJD is complex to manage nationally
The Australian beef industry is unusual in the world being almost free of BJD
Unlike sheep the disease does not cause large economic loss in infected beef herds
It is economically disastrous for a stud herd
If it is ever linked to the similar disease in humans, Chrones disease, the BJD status of beef cattle in Australia will be very important
2
BJD is complex to manage nationally
Control/management of the disease is by state based legislation
Some states such as WA are BJD free and others such as SA, NSW, Vic and Tas have some infected herds
Animal Health Australia is the National Co-ordinator of BJD management
BJD is managed by state legislation which limit the trade of breeding cattle between states.
WA only accepts Monitored Negative 3 cattleQld/NT accept cattle from BJD protected Zones (NSW and pastoral zones of SA)NSW accepts cattle from “Beef Only”herds in the BJD Control (SA) & Management Zones (Vic and Tas)
3
Changed Zones commenced on 1 July
2012 Review of audit procedures for MAP herds
DNA Update – Testing Options Available for Australian Cattle Breed Associations
Emily PiperDirector, AGLThe University of Queensland
Australian Registered Cattle Breeders’ Association, AGM 2012, Brisbane
DNA TESTING @ UQ
• The Animal Genetics Laboratory at The University of Queensland is a service laboratory that specialises in genotyping, parentage assignment and assay development
• Summary of Presentation:
• Summary of currently available / standard testing
• Update on SNP parentage from ISAG meeting
• Update on the Poll test
• Options in the genomics space
• Sample types
• Where can I find the relevant information?
DNA TESTING @ UQ
• Standard DNA Testing Available at UQ
• Parentage testing (microsatellite analysis)
• Recessive Disorders / Conditions• Angus / Murray Grey – AM, NH, CA
• Hereford – HY, DI*, IE*
• Dexter – BD1, BD2, PHA
• Many more available at EMAI
• Qualitative Traits• F94L myostatin
• Coat Colour (red/black)
• Horn/Poll marker
UPDATES FROM ISAG
• International Society for Animal Genetics – ISAG• Stipulates the ‘international standards’ for parentage testing
• Bi-annual meeting recently held in Australia, July 2012
• Discussions surrounding SNP markers for parentage• ISAG has taken 100 SNP (developed by USDA) as the standard
• These are not appropriate for Bos indicus breeds
• Work from Labogena (France) suggests more markers are needed for more accurate parentage assignment (~175 markers)
• 500 Calves, 500 Sires:
# of SNP 200 175 150 125 100 75 50% With Sire
Assigned100 100 99 99 99 99 91
% Correct Sire Assignment
100 100 93 78 57 32 13
UPDATES FROM ISAG
• Considerations with SNP Parentage
• Many markers used, accept that there will be ~1-2% error in genotyping
• 100 markers recommended by ISAG, a minimum of 95 markers to be reported
• A backup panel of 100 markers has been recommended (but no standard currently exists)
• The current 100-SNP ISAG panel has an Exclusion Probability equivalent to around 15-18 microsatellite markers (in dairy & Angus)
• Inevitable that a back-up panel will be required to resolve a proportion of cases
UPDATES FROM ISAG
• Considerations with SNP Parentage• Issues surrounding the development of the current ISAG panel on Bos taurus breeds (mainly Angus) – implications for usefulness in more distant breeds
UPDATES FROM ISAG
• Considerations with SNP Parentage• Issues surrounding the development of the current ISAG panel on Bos taurus (mainly Angus) breeds – implications for usefulness in more distant breeds
UPDATES FROM ISAG
• Considerations with SNP Parentage• Microsatellite profiles are not interchangeable** with SNP profiles – consider that parents may have to be re-genotyped
• USDA working on methods to impute microsatellite genotypes from high-density SNP data (Tad Sonstegard lab)
• 99% accurate for dairy breeds
• Still work to be done on beef breeds (AGL / AGBU / CRC contributing genotypes to the project)
• Only the 12 ISAG standards to be included in this method• (so not appropriate for inclusion in multi-sire testing)
• Useful for when animals are dead/unavailable for re-sampling
• Re-genotyping parents recommended
UPDATES ON THE POLL MARKER
• CRC released a marker for poll status in mid-2010• Now available commercially through Pfizer & AGL
• Large validation across breeds undertaken in 2011 – demonstrated need to improve the test for some breeds
• Recent work has demonstrated the utility of additional markers and a “haplotype approach”
• Funding in the pipeline to build the Haplotype Library to deliver a commercial offering by early-2013
• will significantly improve the accuracy / utility of the test for many breeds
• AGBU host the haplotype library and provide updates to the predictions (computationally more complicated than the current test)
• A centrally-hosted database & software will allow other service providers to offer the test with the same accuracy
• AGL to execute a desktop version of the application by October
OPTIONS IN THE GENOMICS SPACE
• High density SNP information incorporated into Breedplan• Delivery of genomic-assisted EBVs
• 50K or 10K genotypes available through AGL
Tail hair sample
Send to Lab
50K / 10K Raw Genotype
National Genomic Database
Genomic-enhanced EBV
Parentage, recessives, pollSelection
OPTIONS IN THE GENOMICS SPACE
• High density SNP information incorporated into Breedplan• Delivery of genomic-assisted EBVs
• 50K or 10K genotypes available through AGL
Tail hair sample
Send to Lab10K Raw Genotype
National Genomic Database
Genomic-enhanced EBV
Parentage, recessives, poll
Selection Igenity MBVRaw Genotype
OPTIONS IN THE GENOMICS SPACE
• Two high-density options relevant to Breed Societies:• Standard Illumina 50K
• Custom GeneSeek 10K – ‘genomic profiler’
• Genomic profiler:• Standard Illumina 7K plus ‘add-ons’
• Recessive disorders
• Additional markers for imputation (7K to 50K)
• Poll*, coat, myostatin
• Markers for imputing microsatellite genotypes*
• ~$45 = base genotype, imputation markers (for 50K imputation), parentage, myostatin
• Additional fees for recessives, poll, coat, imputation to MS profile, Igenity MBVs
OPTIONS IN THE GENOMICS SPACE
• Low Density Options• What if I just want parentage and a recessive test?
• 100 SNP (parentage)
• Recessives
• Coat, Myostatin
• Poll – down the track
• Pick and choose: Parentage + Coat etc ($25-$30)
• No genomic data to Breedplan
• Process will be the same as the current testing (hair to lab → results to association)
Sequenom Panel
SUMMARY
• The AGL can provide
• Genotyping & results for parentage, recessives, qualitative traits
• Genotyping for the Illumina high density arrays• Organise transfer of data to relevant MBV / gEBV provider
• Report parentage, recessive status, qualitative traits directly to association
• Genotyping for low-density panels of SNP• Parentage, recessives, qualitative traits (bundles)
SAMPLE TYPES
• We like hair.
• New products on the market for DNA collection• DNA Genotek – Nasal Swabs ~$7 ea
• ITL / Tego – Blood Cards ~$4 ea
• AllFlex / Zee Tags – Ear Punch ~$? ea
• All are marketed around the ease of collection, particularly in conjunction with ear-tagging procedures
• We will process whatever is sent in, up to individuals / associations to determine what suits their purposes best
• Considerations given to cost, storage, need for testing down the track…
NEED MORE INFO?
• Breed Associations & Societies• Will have the most relevant information for your breed
• SBTS & TBTS• Can provide technical information on Breedplan and the integration of genomic information
• Beef CRC Legacy Website• Many fact sheets available on the current tests (genomics, recessive, qualitative)
• Animal Genetics Lab• Happy to answer questions on the testing process, sample types etc
THANK YOU
School of Veterinary ScienceThe University of Queensland
Gatton QLD 4343(07) 5460 1960
cattleDNA@uq.edu.au
1
What can Pfizer offer Breed Associations
Seminar Session ‐38th ARCBA’s AGM, 8th of August 2012‐
Matias Suarez
2
Summary of the Presentation
Pfizer Animal Genetics
Integration in to Pfizer Animal Health
Products and Services
Questions
3
Pfizer Animal Genetics (2008 ‐ early 2012)
4
Pfizer Animal Health (PAG Integration)
Locally integratedLocally
integrated
Globally integratedGlobally integrated
5
PAH Marketing structure for PAG Products/Services
Directly responsible for PAG products Indirectly responsible for PAG products
6
PAH Sale‐force structure for AG products
Directly responsible for PAG products
6 Managers
30 Professional Sales Representatives
6 Managers
30 Professional Sales Representatives
7
PAH Technical Services structure for AG Products
Directly responsible for PAG products Indirectly responsible for PAG products
8
Global Laboratory Operations
Located in Australia
9
Global Research & Development
Located in Australia
VMRDVMRD
10
Geographical location
Office & Customer Service
Commercial/ Business
Research & Development
11
Products and Services
Products
• Genotypes
Services
• Parent Verification / Traceability• Qualitative Traits• Quantitative Traits
12
Products
• Genotypes
• Illumina® genotyping assays• BovineHD Beadchip: HD genotyping with 777,962 SNPs
• Bovine SNP50 Beadchip: 54,609 SNPs
• BovineLD Beadchip: 6,909 SNPs
• Other platforms• USDA Parentage 96 SNPs
13
Parent Verification
• Critical for pedigree integrity • EBV calculation
• Tracking of Genetic Defects
• Ease of management• Multi‐sire matings
• AI/Backup bull scenario
• Mothering up
• Tools currently being used• STRs & SNPs
14
Traceability & Breed Verification
15
Qualitative Traits
• Genetic Conditions
• Arthrogryposis Multiplex (AM)
• Neuropathic Hydrocephalus (NH)
• Congenital Contractural Arachnodactyly (CA)
• among others......
• Polledness
• Association test developed by Beef CRC
• Coat Colour
16
Quantitative Traits
• High Density panels
• HD50K for Angus
• Sheep 50K
• CLARIFIDE NAPCo
• Low Density panels
• CLARIFIDE Holstein
• Targeted panels
• GeneSTAR
• CLARIFIDE Nelore
• GeneMAX
17
Products timeline
2010 2011 2012
Brahman
Beef CRCIII products
CLARIFIDE Dairy AUS
CLARIFIDE Nelore enhancements
HD50K for Red Angus
Shepherd SNP
18
In Summary: What can we offer Breed Associations
• Australian Pfizer Animal Health’s “machine”
– Marketing expertise
– Sale force
– In field Technical Support
• Pfizer’s Research & Development
– Unmatched expertise & investment
• Unmatched line of Products / Services
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