how the genomic evaluation program works

G.R. WiggansAnimal Improvement Programs LaboratoryAgricultural Research Service, USDA Beltsville, MD

[email protected]. WiggansGenomics: Emerging Markets Program (1)

How the genomic evaluation program works

G.R. Wiggans 2009Genomics: Emerging Markets Program (2)

Short history

Illumina BovineSNP50™ BeadChip developed

Accuracy of genomic information assessed by using 2004 evaluations of bulls born before 2000 to predict 2009 evaluations of young bulls

Unofficial genomic evaluations of bull calves provided to industry beginning in April 2008

Jersey results released in October 2008

New results released every 2 months

Nearly 23,000 animals genotyped through Mar. 2009


What is a SNP?

Single-nucleotide polymorphism

Place on the chromosome where animals differ in the nucleotides (A, C, T, or G) they have

Usually not part of the gene that controls a trait – quantitative trait locus (QTL)

With enough SNPs, association between SNP alleles and QTL alleles gives useful evaluations

SNPs chosen to be distributed evenly and have both alleles well represented in population


Source of genomic evaluations

DNA extracted from blood, hair, or semen

~40,000 genetic markers (SNPs) evaluated

For each SNP, difference in PTA estimated between animals with 1 allele compared to the other allele

Genomic evaluation combines SNP effect estimates with existing PA or PTA

Genomic data contribute ~11 daughter equivalents to reliability


SNP edits and counts

Illumina SNP50 BeadChip 58,336Insufficient number of beads

1,389

Unscorable SNP 4,360Monomorphic in Holsteins 5,734Minor allele frequency <5%

6,145

Not in H-W equilibrium 282Highly correlated 2,010Used for genomic prediction

38,416


How to get animals genotyped

Participating AI organizations have 5-year exclusive right to evaluate bulls genomically

Each AI organization genotypes first-choice flushes, thereby usually avoiding duplicate genotypes

Web-based system collects nominations Avoid duplication Confirm validity of ID and pedigree Associate sample ID with animal ID

Breed associations offer cow genotyping service


Steps to prepare genotypes

Nominate animal for genotyping; confirm not already genotyped

Collect hair, blood, or semen from animal Blood not suitable for twins

Send to laboratory for extraction

Transfer DNA to BeadChip (12 samples/chip) for 3-day genotyping process


Steps to prepare genotypes (cont.) Read red/green intensities from chip

Transfer intensity files to AIPL for calling genotypes

Check genotypes for duplicates, parent-progeny conflicts, and wrong sex


DNA laboratories

Research Bovine Functional Genomics Laboratory (BFGL),

USDA (Beltsville, MD) University of Alberta (Edmonton, AB, Canada) University of Missouri (Columbia, MO) Illumina (San Diego, CA)

Commercial (some do extraction only) GeneSeek (Lincoln, NE) Genetics & IVF Institute (Fairfax, VA) Genetic Visions (Middleton, WI) DNA LandMarks (Saint-Jean-sur-Richelieu, QC,

Canada) Maxxam Analytics (Mississauga, ON, Canada) ABS (DeForest, WI, through SyGen/PIC, Franklin,

KY )


What can go wrong

Sample doesn’t provide adequate DNA quality or quantity

Genotype has many SNPs that can’t be determined (90% call rate required)

Genotype conflicts with parent(s) Pedigree error Sample ID error Laboratory error Genotype checked against all others to find

true parent


Accurate evaluations

Accurate genomic evaluations require estimates of SNP effects

Evaluations with high reliability provide the most information

Recent animals are more useful than ones from earlier generations

Reliability of genomic evaluations increases with number of predictor animals


Genomic evaluation & reliability Calculate parent average (PA) based only

on genotyped animals with best linear unbiased prediction

Combine traditional PA (or evaluation) with genomic PA and evaluation using selection index weights

Update traditional evaluation with additional information from genomics

Reliability from inverse of genomic relationship matrix


Data & evaluation flow

Animal Improvement

Programs Laboratory,

USDA

AI organizations,

breed associations

Dairyproducers

DNAlaboratories

samples

samples

samples

evaluations

genotypes

nominationsevaluations


Genomic vs. traditional PTA

Genotype can be thought of as source of information like parents, progeny, and records

Official PTA that include a genomic contribution are identified

One genotype used to calculate genomic evaluations for all 29 traits

Genomic evaluations used the same as traditional PTA

Expected to increase rate of genetic improvement because of a large decrease in generation interval


Genomic vs. traditional (cont.)

Protein

Net meritBull birth year

Evaluation SD Min. Max. Corr.

1995–2004 Genomic PTA 158 –473 7690.95Traditional

PTA159 –578 778


PA126 –185 772

Bull birth year

Evaluation SD Min. Max. Corr.


PTA17 –61 88


PA12 –27 79


Genomic vs. traditional – protein PTA

0

10

20

30

40

50

1990 1995 2000 2005 2010

Birth year

Pro

tein

PT

A (

lb)

Genomic

Traditional

Traditional PA


Genomic vs. traditional – net merit

-100

0

100

200

300

400

500

1990 1995 2000 2005 2010

Birth year

Net

mer

it (

$)

Traditional

Genomic

Traditional PA


Genomic vs. trad. – protein reliability

0

20

40

60

80

100

1990 1995 2000 2005 2010

Birth year

Pro

tein

rel

iab

ilit

y (%

)

Traditional

Genomic

Traditional PA


0

20

40

60

80

100

1990 1995 2000 2005 2010

Birth year

Net

mer

itre

liab

ility

(%

)

Traditional

GenomicTraditional PA

Genomic vs. trad. – net merit reliability


0

250

500

750

1000

1250

1500

0 10 20 30 40 50 60 70 80 90 100

Protein reliability (%)

Bu

lls (

no

.)Reliability frequencies – young bulls

Genomic PTA

Traditional PA


Collaboration with Canada

Semex

Participated since beginning of genomics research

Contributed genotypes to providing a important increase in accuracy for first test

Genotypes will be shared between AIPL and Canadian Dairy Network

AIPL and University of Guelph collaboration


Collaboration with Canada (cont.) Same set of predictor animals used in

Canada and U.S. so that evaluations of genotyped animals have same accuracy

Canada expects official release of genomic evaluations in August 2009

Common procedures between 2 countries assist in industry acceptance


Use of genomic evaluations

AI organizations determine which young bulls to buy

Considered in selection of mating sires

Impact on bull dam selection will increase

Used to market semen from 2-year-old bulls


January 2009

Genomic evaluations became official

Genotyped ancestors contribute their evaluations to descendants

Evaluations of all genotyped females are public

Evaluations of males enrolled with NAAB or ≥24 months old are public

Young-bull genomic evaluations may be shared among AI organizations or disclosed by owner


Updates between official evaluations Genomic evaluations calculated

approximately every 2 months

Evaluations of animals that already have an official evaluation not released

Evaluations of new animals distributed to owners Females by breed associations Males by NAAB

Usually 1,000–2,000 new genotypes included


Distribution of evaluations

Nomination establishes a requester who receives the genomic evaluation

Requesters 7 participating AI organizations U.S. and Canadian Holstein associations American Jersey Cattle Association Some laboratories

Requesting AI organization can agree to share an evaluation with other AI organizations


Distribution of evaluations (cont.) Evaluations of all females sent to

respective breed associations for distribution to owners

NAAB distributes bull evaluations to owners and manages sharing of evaluations among AI organizations

Genomic evaluations of animals with official evaluations released as unofficial at updates between official evaluations


Impact on producers

Young-bull evaluations with accuracy of early 1st-crop evaluations

AI organizations marketing genomically evaluated 2-year-olds

Bull dams likely to be required to be genotyped

Rate of genetic improvement likely to increase by up to 50%

Progeny-test programs changing


Schedule

Calculate SNP effects with each of 3 annual traditional evaluations

Calculate genomic evaluations once or more between traditional evaluations

Recalculate SNP effects if significant number of predictor animals added

May use existing SNP effects if only young animals added


Improvements

Require bar codes on sample containers to reduce errors and improve lab efficiency

Require animals be enrolled with breed association before DNA sample collected

Process genotypes frequently; check for and report conflicts as received

Reduce processing time by improving efficiency of genotype calling either by laboratories or at AIPL


Calling genotypes

Scanner reads chip recording intensities of red and green

Software converts those to AA, AB, or BB Genotype is missing if assignment is

uncertain

Accuracy can be improved by adjusting for variation in intensity due to SNP and animal

Techniques to automate adjustment are underway

Manual intervention can increase accuracy of calling with current software


Plans to increase accuracy

Genotype more predictor bulls Automatic increase as bulls in waiting receive traditional evaluations

Increase number of SNPs used

Reach 1,500 Brown Swiss through foreign collaboration?

Increase genotyped Jerseys from both domestic animals and possible foreign collaboration


International implications

All major dairy countries investigating genomic selection

Interbull meeting January 2009 discussed how genomic evaluations should be integrated

AI organizations need to find balance between competitive benefits from treating genotypes as proprietary versus sharing

Importing countries must change rules to allow for genomically evaluated young bulls


Longer-term possibilities

Determine inheritance of individual chromosome segments (haplotyping) May allow better tracking of QTL

Approximate genotypes of missing ancestors to increase predictor population

Increase number of SNPs or even use entire DNA sequence


Implications

Extraordinarily rapid implementation of genomic evaluations

Young bull acquisition and marketing now based on genomic evaluations

Genomic evaluations may allow more cows from commercial herds to be used as bull dams


Financial support

National Research Initiative grants, USDA NAAB (Columbia, MO)

ABS Global (DeForest, WI) Accelerated Genetics (Baraboo, WI) Alta (Balzac, AB) Genex (Shawano, WI) New Generation Genetics (Fort Atkinson, WI) Select Sires (Plain City, OH) Semex Alliance (Guelph, ON) Taurus-Service (Mehoopany, PA)

Holstein Association USA (Brattleboro, VT) American Jersey Cattle Association

(Reynoldsburg, OH) Agricultural Research Service, USDA

how the genomic evaluation program works

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