curt van tassell bovine functional genomics laboratory agricultural research service, usda...
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Curt Van TassellBovine Functional Genomics LaboratoryAgricultural Research Service, USDA Beltsville, MD
[email protected] Genomics for Sustainable Livestock Breeding (1)
The use of SNP chips for selection of dairy cattle
Applied Genomics for Sustainable Livestock Breeding (2)
A Little History…
1908
1936
1989
1997
2009
USDA organizes a national milk-recording program based on success in Michigan
The first national sire evaluations are calculated from daughter-dam comparisons
Animal model evaluations use the relationships among all cows and bulls
InterBULL evaluations introduced to incorporate foreign daughter information
First official genetic evaluations incorporating genomic data
Applied Genomics for Sustainable Livestock Breeding (3)
History of genomic evaluations
Oct. 2007 BovineSNP50 BeadChip available
Apr. 2008 First unofficial evaluation released
Jan. 2009 Genomic evaluations official forHolstein and Jersey
Aug. 2009 Official for Brown Swiss
Sept. 2010 Unofficial evaluations from 3K chip
released
Dec. 2010 3K genomic evaluations official
Applied Genomics for Sustainable Livestock Breeding (4)
Genome Selection
“Train” system using phenotypic and genotypic data
Large regression system
Predict genetic merit at birth by combining pedigree merit and merit predicted from SNP
Final genetic predictions are transparent to technology
Applied Genomics for Sustainable Livestock Breeding (5)
Genomic Prediction
Applied Genomics for Sustainable Livestock Breeding (6)
What’s a SNP genotype worth? Pedigree information ~7
daughters
SNP information ~34 daughters for protein yield (h2 = 0,30)
SNP information ~ 31 daugthers for fertility (h2 = 0,04)
Applied Genomics for Sustainable Livestock Breeding (7)
Reliability Gain1 by Breed
Trait HO JE BS
Net merit 23 9 3
Milk 23 11 0
Fat 33 15 5
Protein 22 4 1
Fat % 43 41 10
Protein % 34 29 5
1Gain above parent average reliability ~35%
Yield traits and NM$ of young bulls
Applied Genomics for Sustainable Livestock Breeding (8)
Genotyped Holsteins
DateAll
animalsBulls Cows Bulls Heifers
04-10 9,770 7,415 16,007 8,630 41,82208-10 10,430 9,372 18,652 11,021 49,47509-10 10,611 9,453 19,389 13,333 52,78610-10 10,616 9,787 20,184 15,288 55,87711-10 10,619 10,175 20,836 17,095 58,72712-10 11,293 12,825 21,161 18,336 63,61501-11 11,194 13,582 22,567 22,999 70,34202-11 11,196 13,935 23,330 26,270 74,73103-11 11,713 14,382 24,505 29,929 80,52904-11 12,152 11,224 25,202 36,545 85,123
Traditional evaluationNo traditional evaluation
Applied Genomics for Sustainable Livestock Breeding (9)
Training Bulls
1950
1970
1981
1983
1985
1987
1989
1991
1993
1995
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2005
2007
0
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Year of Birth
Applied Genomics for Sustainable Livestock Breeding (10)
50K Genotypes
2009
-04
2009
-06
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-08
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-10
2010
-01
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-02
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-04
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-05
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-06
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-03
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-04
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-05
0
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F-Yng M-Yng F-Old M-Old
Applied Genomics for Sustainable Livestock Breeding (11)
3K Genotypes
2010-09
2010-10
2010-11
2010-12
2011-01
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2011-03
2011-04
2011-05
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F-Young M-Young F-Old M-Old
Applied Genomics for Sustainable Livestock Breeding (12)
April Genotypes – Holstein
0
500
1000
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2000
1998-2006 2007 2008 2009 2010 2011
Birth year
Nu
mb
er o
f G
enot
ypes
3K Females 3K Males 50K Females 50K Males
Applied Genomics for Sustainable Livestock Breeding (13)
Holstein Bulls
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2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Birth Year
Nu
mb
er o
f B
ull
s
Total 10 Herds Genotyped Both
Applied Genomics for Sustainable Livestock Breeding (14)
Reliabilities for young animals*
*Animals with no traditional PTA in March 2011
0
5
10
15
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30
3K genotype50K genotype
Reliability for PTA protein (%)
An
imals
(%
)
Applied Genomics for Sustainable Livestock Breeding (15)
Determination of Reliability
Sum of genomic relationships with the predictor animals weighted by reliability
Call rate
Expected imputation error rate
Reliability of parent average
Larger impact if dam not genotyped
Applied Genomics for Sustainable Livestock Breeding (16)
Use of genomic evaluations
Determine which young bulls to bring into AI service
Use to select mating sires
Pick bull dams
Market semen from 2-year-old bulls
Applied Genomics for Sustainable Livestock Breeding (17)
Use of 3K genomic evaluations
Sort heifers for breeding Flush Sexed semen Beef bull
Confirm parentage to avoid inbreeding
Predict inbreeding depression better
Precision mating considering genomics (future)
Applied Genomics for Sustainable Livestock Breeding (18)
Results
Applied Genomics for Sustainable Livestock Breeding (19)
2009 Genomic Milk
-1500 -1000 -500 0 500 1000 1500 2000 2500 3000 3500
-2000
-1500
-1000
-500
0
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3000
f(x) = 0.854747985183735 x − 411.006010504377R² = 0.656057220000062f(x) = 0.803548436861551 x − 341.513603873803R² = 0.473797337393081
Traditional
Linear (Tradi-tional)
Genomic
Linear (Genomic)
Applied Genomics for Sustainable Livestock Breeding (20)
2009 Traditional Milk
-1000 -500 0 500 1000 1500 2000 2500 3000
-2000
-1500
-1000
-500
0
500
1000
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2500
3000
f(x) = 0.83221442474764 x − 495.740571838771R² = 0.36912984168143
f(x) = 0.872532261521668 x − 533.610454732522R² = 0.331569529092576
Traditional
Linear (Tradi-tional)
Genomic
Linear (Genomic)
Applied Genomics for Sustainable Livestock Breeding (21)
Response to Selection - Milk
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10
500
1000
1500
2000
2500
Gen 2009 Trad 2009
Fraction Selected
Applied Genomics for Sustainable Livestock Breeding (22)
Response to Selection - Milk
0 0.005 0.01 0.015 0.02 0.025 0.03 0.035 0.04 0.045 0.050
500
1000
1500
2000
2500
Gen 2009 Trad 2009
Fraction Selected
Applied Genomics for Sustainable Livestock Breeding (23)
Response to Selection – SCS
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 12.5
2.6
2.7
2.8
2.9
Gen 2009 Trad 2009
Fraction Selected
Applied Genomics for Sustainable Livestock Breeding (24)
Response to Selection – SCS
0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.12.4
2.5
2.6
2.7
2.8
Gen 2009 Trad 2009
Fraction Selected
Applied Genomics for Sustainable Livestock Breeding (25)
Future
Applied Genomics for Sustainable Livestock Breeding (26)
Increase in accuracy
Genotyped bulls get traditional evaluation when 5 years old
Possible genotyping of 10,000 bulls with semen in CDDR
Collaboration with more countries
Use of more SNP from HD chips
Full sequencing
Applied Genomics for Sustainable Livestock Breeding (27)
Application to more traits
Animal’s genotype is good for all traits
Traditional evaluations required for accurate estimates of SNP effects
Traditional evaluations not currently available for heat tolerance or feed efficiency
Research populations could provide data for traits that are expensive to measure
Will resulting evaluations work in target population?
Applied Genomics for Sustainable Livestock Breeding (28)
High density (HD) genotypes
Illumina Bovine HD BeadChip available
777,962 SNP Collaborations with GBR, ITA, & CAN to
provide genotypes Over 400 genotypes from research
projects in database
Affymetrics HD
648,855 SNP
Optimized for genetic coverage
NAAB negotiating plan for use
Applied Genomics for Sustainable Livestock Breeding (29)
Use of HD
Some increase in accuracy from better tracking of QTL
Potential for across breed evaluations
Requires few new HD genotypes once adequate base for imputation developed
Imputation improvements were particularly beneficial in imputing HD
Applied Genomics for Sustainable Livestock Breeding (30)
Low-Plex Genotyping
Need cost-effective genotyping platform for application to commercial cows
<$5 / animal
Applications:
Parentage, traceability
Relatedness
Targetted panels
Applied Genomics for Sustainable Livestock Breeding (31)
Genome Sequencing?
Whole-genome sequences on individuals will be available in the next few years
How will we store and use those data?
Not feasible to calculate effects for 3,000,000,000 nucleotides or even 3,000,000 SNP
May be best to fine map then target genotype…
Applied Genomics for Sustainable Livestock Breeding (32)
Exome Sequencing?
Capture and sequence coding part of genome and regulatory regions
~50-60 Mb
Higher likelihood of functional SNPs
Less data than complete sequence
Soon price difference irrelevant?
Applied Genomics for Sustainable Livestock Breeding (33)
Summary
Extraordinarily rapid implementation of genomic evaluations
Young-bull acquisition and marketing now based on genomic evaluations
Genotyping of many females because of 3K chip
Applied Genomics for Sustainable Livestock Breeding (34)