2007 paul vanraden, george wiggans, animal improvement programs laboratory curt van tassell, tad...

2007

Paul VanRaden, George Wiggans, Paul VanRaden, George Wiggans, Animal Improvement Programs Laboratory Curt Van Tassell, Tad Sonstegard, Bovine Functional Genomics LaboratoryUSDA Agricultural Research Service, Beltsville, MD, USA Flavio ShenkelCGIL, University of Guelph, Guelph, ON, [email protected]

2009

Benefits from Cooperation in Benefits from Cooperation in Genomics Genomics

Interbull Genomics Workshop, Jan. 2009 (2) Paul VanRaden200

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TopicsTopics

Genomic cooperation• Simulation of very large population• Proposals for genotype sharing• Country border issues and North American

experience• Genomic MACE equations

USA update• Actual HOL, JER, and BSW results• Database and implementation


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Cooperative International ProjectsCooperative International Projects

Traditional genetic evaluations• MACE instead of merging phenotypes• Small benefits expected from data merger• Proven bulls only, not cows or young bulls

Parentage testing, genetic recessives, pedigrees done by breed associations

Genomics: what role for Interbull?


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Sequencing of GenomesSequencing of Genomes

Species Year

Human - $3 billion 2000

Cow - $53 million funded by: 2004

50% Nat’l Human Genome Res Inst

50% USA, CAN, AUS, NZL

Chicken 2004

Pig - < $20 million 2009


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Human DNA Data SharingHuman DNA Data Sharing

"The highest priority of the International Human Genome Sequencing Consortium is ensuring that sequencing data from the human genome is available to the world's scientists rapidly, freely and without restriction." National Human Genome Research Institute, 2008

"The principle of rapid pre-publication release should apply to other types of data from other large-scale production centers." Wellcome Trust, 2003


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SimulationSimulation Results ResultsWorld Holstein PopulationWorld Holstein Population

40,360 older bulls to predict 9,850 younger bulls in Interbull file

50,000 or 100,000 SNP; 5,000 QTL

Reliability vs. parent average REL• Genomic REL = corr2 (EBV, true BV) • 81% vs 30% observed using 50K• 83% vs 30% observed using 100K


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Genotype Exchange OptionsGenotype Exchange Options

Give away for free (not likely) Genotype own bulls, then trade?

• Trade an equal number or all bulls?• Country A has 5000 and B has 1000• Proportional to population size?

Trade among organization pairs or create central genomic database?

Service fee for young animals to pay for ancestor genotyping?


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Problems of Not SharingProblems of Not Sharing

Genetic progress not as fast as with full access to genotypes

Severe limits on researcher access to genotypes (secrecy)

Genomics may lead to natural monopoly, similar to railroads• Small companies / countries can’t

afford to buy sufficient genotypes


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Share Young Bull, Cow Genotypes?Share Young Bull, Cow Genotypes?

May be marketed in >1 country

Exchange of young animals and females more important as their REL increases with genomics

Helps to synchronize databases

Could lead to joint evaluation


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North American Cooperation North American Cooperation

174 markers, 1068 USA and CAN bulls• Illinois, Israel, and USDA researchers• 1991-1999

367 markers, 1415 USA and CAN bulls• USDA, Illinois, and Israel• 1995-2004

38,416 markers, 19,464 animals• USDA, Missouri, Canada, and Illumina• Oct 2007- Dec 2008


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Country BordersCountry Borders

Most phenotypic data collected and stored within country

Genomic data allows simple, accurate prediction across borders• Need traditional EBV or PA for foreign

animals, but not available for young bulls, cows, or heifers

• May need full foreign pedigrees• Genomic evaluations official on USA scale

for many foreign animals (not just CAN)


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Foreign DNA in North American DataForeign DNA in North American DataProven bulls, Young bulls, and FemalesProven bulls, Young bulls, and Females

Ctry old yng fem Ctry old yng fem

NLD 25 134 53 GBR 7 7 1

DEU 22 31 64 DNK 5 5 0

ITA 14 17 5 LUX 0 0 8

AUS 12 30 0 BEL 3 1 0

HUN 6 29 2 CHE 4 0 0

FRA 12 19 2 NZL 4 0 0

CZE 3 15 0 FIN 1 0 0


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USA UpdateUSA Update

Genomic PTAs official in January• Traditional PTAs sent to Interbull• MACE used if foreign dtrs included• Genomic info used for most bulls• Genomic PTA transferred to

descendants (to ancestors in future)

Jersey results also are official More Brown Swiss needed (CHE)


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Genomic MethodsGenomic Methods

Direct genomic evaluation• Sum of effects for 38,416 genetic markers• Not published

Combined genomic evaluation• Include phenotypes of non-genotyped

ancestors by selection index

Transferred genomic evaluation• Propagate info from genotyped animals to

non-genotyped relatives by selection index


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Genotyped Animals (n=19,464)Genotyped Animals (n=19,464)As of December 2008As of December 2008

0

500

1000

1500

2000

2500

1950

1970

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

Year of Birth

Nu

mb

er

of

An

ima

ls Predictor

Predictee

Young


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Experimental Design - UpdateExperimental Design - UpdateHolstein, Jersey, and Brown Swiss breedsHolstein, Jersey, and Brown Swiss breeds

HOL JER BSW

Predictor:

Bulls born <2000 4,422 1,149 225

Cows with data 947 212

Total 5,369 1,361 225

Predicted:

Bulls born >2000 2,035 388 118

Data from 2004 used to predict independent data from 2009


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Reliability GainReliability Gain11 by Breed by BreedYield traits and NM$ of young bullsYield traits and NM$ of young bulls

Trait HO JE BS

Net merit 24 8 3

Milk 26 6 0

Fat 32 11 5

Protein 24 2 1

Fat % 50 36 10

Protein % 38 29 5

1Gain above parent average reliability ~35%


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Reliability Gain by BreedReliability Gain by BreedHealth and type traits of young bullsHealth and type traits of young bulls

Trait HO JE BS

Productive life 32 7 2

Somatic cell score 23 3 16

Dtr pregnancy rate 28 7 -

Final score 20 1 -

Udder depth 37 18 3

Foot angle 25 8 -

Trait average 29 11 N/A


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Value of Genotyping More AnimalsValue of Genotyping More AnimalsActualActual and and predictedpredicted gains for 27 traits and for Net Merit gains for 27 traits and for Net Merit

Bulls Reliability Gain

Predictor Predicted NM$ 27 trait avg

2130 261 13 17

2609 510 17 18

3576 1759 23 23

4422 2035 24 29

6184 7330 31 30

Cows:

947

1916


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Genomic MACEGenomic MACEGenomics Task Force, Pete SullivanGenomics Task Force, Pete Sullivan

Residuals correlated across countries• Repeated tests of the same major gene, or• SNP effects estimated from common bulls• Let cij = proportion of common bulls • Let gi = DEgen / (DEdau + DEgen)• Corr(ei, ej) = cij * Corr(ai, aj) * √(gi * gj)

Avoids double counting genomic information from multiple countries i, j

New deregression formulas needed


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ConclusionsConclusions

Reliability for young animals• 30-38% for traditional parent averages• 60-70% genomic REL for USA HOL traits• 81% using 40,360 simulated bulls• 83% using 100K instead of 50K markers

High reliability requires large numbers of genotyped animals• Gains much smaller for USA JER and BSW breeds

Trading, sharing, profit is needed Revised MACE may include genomics


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AcknowledgmentsAcknowledgments

Genotyping and DNA extraction:• USDA Bovine Functional Genomics Lab, U.

Missouri, U. Alberta, GeneSeek, Genetics & IVF Institute, Genetic Visions, and Illumina

Computing: • AIPL staff (Mel Tooker, Leigh Walton, Jay

Megonigal) Funding:

• National Research Initiative grants– 2006-35205-16888, 2006-35205-167012006-35205-16888, 2006-35205-16701

• Agriculture Research Service• Holstein and Jersey breed associations• Contributors to Cooperative Dairy DNA Repository

(CDDR)


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CDDR ContributorsCDDR Contributors

National Association of Animal Breeders (NAAB, Columbia, MO)• ABS Global (DeForest, WI)• Accelerated Genetics (Baraboo, WI)• Alta (Balzac, AB, Canada)• Genex (Shawano, WI)• New Generation Genetics (Fort Atkinson, WI)• Select Sires (Plain City, OH)• Semex Alliance (Guelph, ON, Canada)• Taurus-Service (Mehoopany, PA)

2007 paul vanraden, george wiggans, animal improvement programs laboratory curt van tassell, tad...

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