why genomics works and what is coming
DESCRIPTION
Why genomics works and what is coming. What is genomics?. Study of the effects of an animal’s genes Evaluations are based on DNA markers Single-nucleotide polymorphism (SNP) markers are abundant and cheap to read Illumina BovineSNP50 BeadChip provides genotypes for >50,000 (50K) SNP - PowerPoint PPT PresentationTRANSCRIPT
G.R. WiggansAnimal Improvement Programs LaboratoryAgricultural Research Service, USDA Beltsville, MD
[email protected]. WiggansADSA 18th DISCOVER Conference – 2009 (1)
Why genomics works and what is coming
G.R. WiggansADSA 18th DISCOVER Conference – 2009 (2)
What is genomics?
Study of the effects of an animal’s genes
Evaluations are based on DNA markers
Single-nucleotide polymorphism (SNP) markers are abundant and cheap to read
Illumina BovineSNP50 BeadChip provides genotypes for >50,000 (50K) SNP
Possible genotypes across 2 chromosomes at each SNP are AA, AB, and BB
G.R. WiggansADSA 18th DISCOVER Conference – 2009 (3)
What is whole-genome selection? Many markers used to track inheritance
of chromosomal segments
Impact of each segment estimated for each trait
Estimates combined with traditional predicted transmitting ability (PTA) to produce genomic evaluation (GPTA)
Animals can be selected shortly after birth
G.R. WiggansADSA 18th DISCOVER Conference – 2009 (4)
What is a SNP?
Place on the chromosome where animals differ in their DNA nucleotides (A, C, T, or G)
Usually not part of the gene that controls a trait – quantitative trait locus (QTL)
With enough SNPs, association between SNP and QTL alleles allows useful genetic evaluation
SNPs chosen to be distributed evenly and have both alleles well represented in the population
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Source of genomic evaluations
DNA extracted from blood, hair, or semen
43,385 SNPs evaluated
SNP effect is difference in PTA from having 1 more A (BB v AB or AB v AA)
Genomic evaluation combines SNP effect estimates with existing parent average (PA) or PTA
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Genotyping preparation
Nominate animal for genotyping
Collect hair, blood, or semen from animal Blood may not be suitable for twins
Send to laboratory for DNA extraction
Transfer DNA to BeadChip (12 samples/chip) for 3-day genotyping process
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Genotyping
Read red/green intensities from chip
Call genotypes from intensity file
Check genotypes: Duplicates Parent-progeny conflicts Wrong Breed Wrong sex
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Clustering adjustment … before
86%
callrate
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Clustering adjustment … after
100%
callrate
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Genotype for Elevation
Chromosome 1
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Genotype for inbred bull (Megastar) Chromosome 24
Double grandso
n of Aerostar
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What can go wrong
Sample does not provide adequate DNA quality or quantity
Genotype has many SNPs that can’t be determined (90% call rate required)
Parent-progeny conflicts Pedigree error Sample ID error Laboratory error Unrelated animal qualifies as parent or
progeny
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Parent-progeny conflict
Parent
10212002101201211001020120100
Progeny
10202010100200221001120120220
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Bull
202220200002022220002020222020202
Cow
120120121222201011102221021021202
X chromosome
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Data & evaluation flow
Animal Improvement
Programs Laboratory,
USDA
AI organizations,
breed associations
Dairyproducers
DNAlaboratories
samples
samples
samples
genotypes
nominationsevaluations
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Protein PTA
0
10
20
30
40
50
1990 1995 2000 2005 2010
Birth year
Pro
tein
PT
A (
lb)
Genomic
Traditional
Traditional PA
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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
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0
250
500
750
1000
1250
1500
0 10 20 30 40 50 60 70 80 90 100
Protein reliability (%)
Bu
lls (
no
.)Reliabilities for young bulls
Genomic PTA
Traditional PA
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Actual results from 50K chip
High correlation between genomic merit in November 2004 and August 2009 merit that includes performance
Bull with highest genomic net merit in November 2004 (Man O Man) now ranks 4th of 1,925 bulls
Bull with highest genomic net merit in January 2009 (Freddie) now ranks 2nd
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Use of genomic evaluations
Determine which young bulls to bring into AI
Aid in selection of mating sires
Increasing impact on bull dam selection
Market semen from 2-year-old bulls
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Updates between official evaluations Genomic evaluations calculated every 2
months
Not released for animals that already have an official evaluation
Evaluations of new animals distributed to owners Females by breed associations Males by NAAB
Usually 2,000 new genotypes included
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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
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International implications
All major dairy countries investigating genomic selection
Interbull working on how genomic evaluations should be integrated
Collaboration within Europe to share genotypes
Prediction accuracy continues to increase with increasing numbers of predictor animals
Importing countries must change rules to allow for genomically evaluated young bulls
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Possible selection of embryos
In vitro fertilization of embryos from immature animals Further reduces generation
interval Not yet feasible
Frozen, genotyped embryo market Cost of genotyping < cost of ET Could replace AI if accuracy high
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Best chromosome 1
-40
0
40
80
120
160
X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Chromosome
Net
mer
it, $
Co-Op Boliver Lisha-ET
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Best chromosome 2
-40
0
40
80
120
160
X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Chromosome
Net
mer
it, $
Kellercrest Earnit Hank
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Best 30 chromosomes
-40
0
40
80
120
160
X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Chromosome
Net
mer
it, $
Genomics Extraordinare
Overall net merit = $3,148
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What may be coming
Approximate (impute) genotypes of missing ancestors to increase predictor population
Increase number of SNPs or even use entire DNA sequence
Impute 600K SNP from current 50K chip
Impute 50K from lower cost, lower density chip
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Application to more traits
Animal’s genotype good for all traits
Traditional evaluations required for accurate estimation of SNP effects
Traditional evaluations not currently available for heat tolerance
Research populations could provide data for traits that are expensive to measure Estimates of SNP effects must be
appropriate for target population
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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
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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) American Brown Swiss Association (Beloit, WI) Agricultural Research Service, USDA