Date post: | 23-Dec-2015 |
Category: |
Documents |
Upload: | maximilian-buck-potter |
View: | 216 times |
Download: | 1 times |
C. P. Van TassellC. P. Van Tassell1,21,2 and and J. B. ColeJ. B. Cole2,2,**
1Bovine Functional Genomics and 2Animal Improvement Programs LaboratoriesAgricultural Research Service, USDABeltsville, MD [email protected]
Walking the Cattle Continuum: Moving From the BovineSNP50 to Higher- and Lower-Density SNP Panels
9th WCGALP, August 2010 (2) Van Tassell and Cole
Introduction
• The Illumina Bovine SNP50 Bead Chip has been very successful
• A new high-density chip with 778K markers is now available
• A low-density chip with 3K markers will be available soon
• Other densities under development
9th WCGALP, August 2010 (3) Van Tassell and Cole
Bovine SNP50 Bead Chip
• The Illumina Bovine SNP50 Bead Chip has been very successful
• 43,382 SNP used for genetic prediction
• 47,645 animals genotyped in the US, many more worldwide
• 2nd generation chip with a slightly different SNP set has been developed
9th WCGALP, August 2010 (4) Van Tassell and Cole
Uses of the SNP50
• Genetic improvement•Genomic prediction•Parentage and breed confirmation
• Scientific research• Improving the assembly•QTL discovery (calving traits, SCS)
•Recessives and causative Recessives and causative mutationsmutations
•Phylogeny
9th WCGALP, August 2010 (5) Van Tassell and Cole
Most Holstein genotypes Feb 2010
Country Reference bulls
Germany 17,000
Netherlands 16,000
France 16,000
Scandinavia (DFS) 16,000
United States 9,300
Canada 8,800
9th WCGALP, August 2010 (6) Van Tassell and Cole
Genotyped Holsteins August 2010
*Traditional evaluation
**No traditional evaluation
Date
Young animals**All
animalsBulls* Cows* Bulls Heifers
04-09 7,600 2,711 9,690 1,943 21,94401-10 8,974 4,348 14,061 6,031 33,41402-10 9,378 5,086 15,328 7,620 37,41204-10 9,770 7,415 16,007 8,630 41,82205-10 9,958 7,940 16,594 9,772 44,26406-10 9,958 8,122 17,507 10,713 46,30007-10 9,963 8,186 18,187 11,309 47,64508-10 10,430 9,372 18,652 11,021 49,475
9th WCGALP, August 2010 (7) Van Tassell and Cole
0500
100015002000250030003500400045005000
60616465666768697071727374757677787980
REL (%) for mlk yield
Bu
lls (
no.)
REL for young Holstein bulls July 2010
9th WCGALP, August 2010 (8) Van Tassell and Cole
Bovine High-Density Bead Chip (HD)
• 778K SNP chosen to•Be evenly spaced• Include some Y-specific SNP• Include mitochondrial SNP
• Utilize across-breed information
• Fine mapping of QTL
• Enhanced performance in Zebu cattle
9th WCGALP, August 2010 (9) Van Tassell and Cole
Collaboration was essential
• Illumina provided:• DNA sequence for
a range of breeds• Pfizer provided:
• DNA sequence of additional breeds
• SNP discovery expertise
• USDA-ARS provided:• DNA and library
construction• SNP discovery
expertise• Assay design
expertise
• University of Missouri• Roslin Institute• UNCEIA (France)• Sao Paulo State
University• University of Milan• Technische
Universitaet Muenchen
• Beef CRC• Embrapa• National University
(Korea)
9th WCGALP, August 2010 (10) Van Tassell and Cole
• Enormous amount of DNA sequence data• ~180-200x genome equivalent coverage• ~600 BILLION base-pairs
• Represents: • ~120 libraries• >300 animals
• Animals from breeds representing:• European and Zebu cattle• Beef and dairy • Temperate and tropically adapted
Data highlights
9th WCGALP, August 2010 (11) Van Tassell and Cole
BFGL-IlluminaDeep SNP Discovery
AngusHolsteinLimousin
JerseyNelore
BrahmanRomagnola
Gir
BFGLGenome Assemblies
NeloreWater Buffalo
PfizerLight SNP Discovery
AngusHolsteinJersey
HerefordCharolais
SimmentalBrahmanWaygu
PartnersDeep SNP Discovery
N’DamaSahiwal
SimmentalHanwoo
Blonde d’AquitaineMontbeliard
9th WCGALP, August 2010 (12) Van Tassell and Cole
• >45 million SNPs discovered• ~6 million were used to design the
high density chip• ~800,000 new SNPs added• Kept almost all of the BovineSNP50 SNPs
• Breed groups included• Holstein, Angus, Nelore, Taurine dairy,
Taurine beef, Indicine, tropically adapted Taurine
• 852,645 total gaps• 850,816 (99.8%) < 20kb• 1,795 >20kb, < 100kb• 34 > 100 kb
High-density chip design
9th WCGALP, August 2010 (14) Van Tassell and Cole
The HD chip in practice
• 777,962 available SNP
• 160 bulls genotyped
• 186,705 SNP edited-out• 1,269 unassigned chromosome• 3,197 low call rate• 1,804 Hardy-Weinberg failures• 115,850 MAF < 0.01• 64,585 uncertain location
• 591,258 useable SNP
9th WCGALP, August 2010 (15) Van Tassell and Cole
Bovine Low-Density Bead Chip (3K)
• 2,900 SNP• Evenly spaced• 2,882 useable SNP• 14 Y-specific SNP• Includes 82 SNP for breed determination
• Expected to ship very soon• Allflex tissue-collection tags to be
released• Canada will use DNA Genotek nasal
swabs
• Large initial use anticipated
9th WCGALP, August 2010 (16) Van Tassell and Cole
• Producing AI sires• Accuracy adequate for initial screening • 50K or HD genotyping for bulls acquired
• Confirm IDConfirm ID• Second-stage selectionSecond-stage selection
• Genotype more candidates for less money
• Parentage verification and pedigree discovery
• Traceability for disease outbreaks
Applications of the 3K chip
9th WCGALP, August 2010 (17) Van Tassell and Cole
Other chips
• 96 SNP parentage chip• Use to identify and correct pedigree
errors• Very low cost
• 384 SNP chip• Use for initial screening of cows• 70 to 80% of benefit of 50K for 10% of
cost with haplotyping and parental genotypes
• 700K SNP Affymetrix chip• Will be cheaper than Illumina HD chip
9th WCGALP, August 2010 (18) Van Tassell and Cole
Illumina chips are [mostly] nested
Bovine HD (700K)
Bovine SNP50 (50K)
Bovine LD (3K)
Missing 5,264 V2 markers
Missing 76 3K markers
SNP50 v 2 (V2)
Missing 7,352 SNP50 markers
50K is missing 14 3K markers
9th WCGALP, August 2010 (19) Van Tassell and Cole
• Impute to highest density
• Calculate SNP effects for all HD SNP
• Account for loss in accuracy due to imputation error
• Store only observed genotypes
• Label evaluations with source of genotype
How do we deal with other chips?
9th WCGALP, August 2010 (20) Van Tassell and Cole
• Predict unknown SNP from known• Measure 3,000, predict 50,000 SNP• Measure 50,000, predict 500,000• Measure each haplotype at highest
density only a few times
• Predict dam from progeny SNP
• Increase reliabilities for less cost
Why impute haplotypes?
9th WCGALP, August 2010 (21) Van Tassell and Cole
• Identify haplotypes in population using many markers
• Track haplotypes with fewer markers
• e.g., use 5 SNP to track 25 SNP • 5 SNP: 22020
• 25 SNP: 2022020002002002000202200
How does imputation work?
9th WCGALP, August 2010 (22) Van Tassell and Cole
Example bull haplotypes chromosome 15
9th WCGALP, August 2010 (23) Van Tassell and Cole
Expected REL with haplotyping
• Actual 3K subset of 50K genotypes• Correlation (50K, 3K) was .95 to .97
• REL PA = 35% , 3K = 63% , 50K = 70%
• Simulated 500K genotypes• REL, all animals 50K = 82.6%, 500K = 84%• REL improved only if >1,000 had 500K
• Gains in reliability above PA• 3K chip gives >80% of 50K REL gain• 50K chip gives >96% of 500K REL gain
9th WCGALP, August 2010 (24) Van Tassell and Cole
0
20
40
60
80
100
PA only 2,500 10,000 25,000 100,000
Number of Bulls
Re
lia
bil
ity 3K
50K
500K
3K to 500K
REL Using 3K, 50K, or 500K SNP
9th WCGALP, August 2010 (25) Van Tassell and Cole
• Whole-genome sequences on individuals will be available in the next 5 years
•How will we store and use those data?
• Not feasible to calculate SNP effects for 3,000,000,000 SNP
• Best application may be SNP identification
Whole-genome sequencing
9th WCGALP, August 2010 (26) Van Tassell and Cole
• Collection of genotypes from universities and public research organization
• 3K genotypes from cooperator herds need to enter the national dataset for reliable imputation
• Encourage even more widespread sharing of genotypes across countries
• Funding of genotyping necessary to predict SNP effects for future chips
• Intellectual property issues
Other genotyping issues
9th WCGALP, August 2010 (27) Van Tassell and Cole
• The 50K chip has been very successful, but other densities are coming
• We are collaboratively developing tools to increase the ability to characterize cattle with both lower and higher density SNP chips
• This technology has the potential to impact the developing world
Conclusions
9th WCGALP, August 2010 (28) Van Tassell and Cole28
iBMAC Consortium
Funding
• USDA/NRI/CSREES• 2006-35616-16697• 2006-35205-16888• 2006-35205-16701• 2008-35205-04687 • 2009-65205-05635
• USDA/ARS• 1265-31000-081D• 1265-31000-090D• 5438-31000-073D
• Merial• Stewart Bauck
• NAAB• Gordon Doak• Accelerated Genetics• ABS Global• Alta Genetics• CRI/Genex• Select Sires• Semex Alliance• Taurus Service
• Illumina (industry)• Marylinn Munson• Cindy Lawley• Diane Lince• LuAnn Glaser• Christian Haudenschild
• Beltsville (USDA-ARS) • Curt Van Tassell• Lakshmi Matukumalli• Steve Schroeder• Tad Sonstegard
• Univ Missouri (Land-Grant)• Jerry Taylor• Bob Schnabel• Stephanie McKay
• Univ Alberta (University)• Steve Moore
• Clay Center, NE (USDA-ARS)• Tim Smith• Mark Allan
• AIPL• Paul VanRaden• George Wiggans• John Cole• Leigh Walton• Duane Norman
• BFGL• Marcos de Silva• Tad Sonstegard• Curt Van Tassell
• University of Wisconsin• Kent Weigel
• University of Maryland School of Medicine
• Jeff O’Connell• Partners
• GeneSeek• DNA Landmarks• Expression Analysis• Genetic Visions
Implementation Team
9th WCGALP, August 2010 (29) Van Tassell and Cole
Questions about different chips?