Genomic Evaluations: Past, Present, and Future

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Genomic Evaluations Past, Present, and Future
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Genetic Improvement

• Driven by genetic evaluation program
• Yield, fitness, type and calving traits evaluated
• Widespread use of AI sires
• Progeny test programs
• Genomics
• Increases rate of improvement by reducing
  generation interval

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Past

• Parentage verification using
• Blood groups
• Microsatellites
• Search for major genes
• Marker assisted selection
• Little value

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History of genomic evaluations

• Dec. 2007 BovineSNP50 BeadChip available
• Apr. 2008 First unofficial evaluation released
• Jan. 2009 Genomic evaluations official for
• Holstein and Jersey
• Aug. 2009 Official for Brown Swiss
• Sept. 2010 Unofficial evaluations from 3K chip
• released
• Dec. 2010 3K genomic evaluations to be official

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Bovine Genome Sequence
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Background Genetic Markers

• A segment of DNA at a unique physical location in
  the genome that varies sufficiently between
  individuals that its inheritance can be tracked
  through families.
• A marker is not required to be part of a gene.

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Genetic Markers

• Allow inheritance to be followed in a region
  across generations
• Single nucleotide polymorphisms (SNP) are the
  markers of choice
• Need lots!
• 3 million in the genome

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Cattle SNP Collaboration - iBMAC

• Develop 60,000 Bead Illumina iSelect assay
• USDA-ARS Beltsville Agricultural Research Center
  Bovine Functional Genomics Laboratory and Animal
  Improvement Programs Laboratory
• University of Missouri
• University of Alberta
• USDA-ARS US Meat Animal Research Center
• Starting 60,800 beads 54,000 useable SNP

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Participants
iBMAC Consortium
Funding Agencies

• Illumina
• Marylinn Munson
• Cindy Lawley
• Christian Haudenschild
• BARC
• Curt Van Tassell
• Lakshmi Matukumalli
• Tad Sonstegard
• Missouri
• Jerry Taylor
• Bob Schnabel
• Stephanie McKay
• Alberta
• Steve Moore
• USMARC Clay Center
• Tim Smith
• Mark Allan

• USDA/NRI/CSREES
• 2006-35616-16697
• 2006-35205-16888
• 2006-35205-16701
• USDA/ARS
• 1265-31000-081D
• 1265-31000-090D
• 5438-31000-073D
• Merial
• Stewart Bauck
• NAAB
• Godon Doak
• ABS Global
• Accelerated Genetics
• Alta Genetics
• CRI/Genex

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Collaboration

• Consortium including universities, government and
  industry contributed to developing chip
• Full sharing of genotypes with Canada
• CDN calculates genomic evaluations on Canadian
  base
• Trading of Brown Swiss genotypes with
  Switzerland, Germany, and Austria
• Collaborations with other countries being
  negotiated

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Whats genomics?

• Study of the effects of an animals genes as a
  whole
• Genomic evaluations based on DNA markers
• Single nucleotide polymorphism (SNP) markers
  abundant and cheap to read
• Genotypes from Illumina BovineSNP50, 3K and HD
  BeadChips
• 3 possible genotypes across 2 chromosomes at each
  SNP (AA, AB, BB) or (2, 1, 0)

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Whats whole-genome selection?

• Many markers used to track inheritance of
  chromosomal segments
• Impact of each segment on each trait is estimated
• Estimates combined with traditional predicted
  transmitting abilities (PTA) to produce genomic
  PTA
• Animals can be selected shortly after birth

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Whats a SNP?

• Place on chromosome where animals differ in
  nucleotides (A, C, T, or G)
• Usually not part of gene that controls trait
  (quantitative trait locus QTL)
• With enough SNP, association between SNP and QTL
  alleles enables useful evaluations
• SNP chosen to be distributed evenly and have both
  alleles well represented in population

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Source of genomic evaluations

• DNA extracted from blood, hair, semen, nasal
  swab, or ear punch
• 43,382 SNP evaluated
• SNP effect is difference in PTA from having 1
  more A allele (BB to AB, or AB to AA)

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Present
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Steps to prepare genotypes

• Nominate animal for genotyping
• Collect DNA containing sample
• Blood may not be suitable for twins
• Send to laboratory for extraction
• Transfer DNA to BeadChip for 3-day genotyping
  process

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Steps to prepare genotypes (cont.)

• Read red/green intensities from chip
• Call genotypes from clusters
• Send genotypes to AIPL
• Check genotypes for duplicates, parent-progeny
  conflicts, breed, and wrong sex

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Before clustering adjustment
86 call rate
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After clustering adjustment
100 call rate
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What can go wrong

• Sample doesnt provide adequate DNA quality or
  quantity
• Genotype has many SNP that cant 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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Parent-Progeny conflicts

• For animal
• Pedigree wrong
• Genotype unreliable (3K)
• For SNP
• SNP unreliable
• Clustering needs adjustment

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Parent-Progeny conflict resolution

• Animal checked against all other genotypes
• Usually true sire is found when there is a
  conflict
• Requester must confirm new parent
• Conflict declared when parent-progeny
  relationship detected that is not in pedigree
• Split embryo duplicate of parent
• Sample ID error on genomic parent/progeny

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Genotype extraction

• For animals with gt 1 genotype, missing values
  filled in from other genotypes
• For split embryos and clones, all assigned the
  same genotype
• SNP level parent-progeny conflicts resolved by
  setting SNP with fewest confirmations to missing

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Chips

• BovineSNP50
• Version 1 54,001 SNP
• Version 2 54,609 SNP
• 43,382 used in evaluations
• 3K
• 2900 SNP
• 2706 used in evaluations
• HD
• 777,963 SNP
• Not yet in use, gt 300 in database

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3K chip

• 2900 SNP mostly from SNP50 chip
• 14 Y Chr SNP included for sex validation
• Evenly spaced across 30 Chr
• Developed to reduce cost of genotyping
• 2706 SNP used after removing poor performers
• Rapid adoption, 3,807 animal genotypes submitted
  for Nov. genomic evaluation

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Imputation

• Based on splitting the genotype into individual
  chromosomes (maternal paternal contributions)
• Missing SNP approximated by tracking inheritance
  from ancestors and descendents
• Imputed Dams increase predictor population
• 3K 50K genotypes merged by imputing SNP not on
  3K

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Genotyped Holsteins
Date Young animals Young animals All animals
Date Bulls Cows  Bulls     Heifers  All animals
04-09 7,600 2,711    9,690       1,943 21,944
01-10 8,974 4,348 14,061      6,031 33,414
02-10 9,378 5,086 15,328      7,620 37,412
04-10 9,770 7,415 16,007      8,630 41,822
05-10 9,958 7,940 16,594      9,772 44,264
06-10 9,958 8,122 17,507    10,713 46,300
07-10 9,963 8,186 18,187 11,309 47,645
08-10 10,430 9,372 18,652 11,021 49,475
09-10 10,611 9,453 19,389 13,333 52,786
10-10 10,616 9,787 20,184 15,288 55,877
11-10 10,619 10,175 20,836 17,095 58,727
  Traditional evaluation No traditional
evaluation
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Genotype for Elevation

• Chromosome 1

10001112200200121110111121111011110011211000201220
02220111120210120021112211002111200111100101101101
02200110022011011200201101020222121122102010011100
01122022122211202112012020100202202000021100011202
01122111211102201111000021220200022101202000221122
01110121001112111021121100201021000220002201000201
10000220221102211210112111012222001211212220020002
00202020122211002222222002212111121002111120011011
10112002022200011120110102111212111020221002112012
11001111102111211021112200010110111020220022111010
20111211110112021021021211011022122001211011211012
02201100222002100211000111002110211011100022200202
21212110002220102002222121221121112002011020200122
22221122120212112101100121101102002200020010020001
11101100121102121211120101012120221010101111102110
21122111111212111210110120011111021111011111220121
01212110102220202121122212022200212121012121020110
0111222121101
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Genotype for inbred bull (Megastar)

• Chromosome 24

10212221010210210111021101121122112110022020002220
20002020220000022002022220220200002002022222200002
02222000002202000020022002000000222200022220000000
00002022202200200022202022222000220222222222000020
02202022202000200022000000002202220000002200202000
22220020200200202022202222222202220200020220220222
20202220202020220002200222022002220000022020000200
20020002002222200022220202002220022202000020200000
02222202020000200200222200020220222200220002222022
00222202020002202202222002220022000200220200000220
02202220000220000220002222020022220002200200202022
02000222000222002220220220000022022002002002022000
20002222022002220020220200222202220000020220002020
02020200022002200000220222002022202000220020002000
22002002000200220222220022022000200002000200002022
00202202002000022200002220020002002220000220220020
02200220220202020202020002220200022020020220222022
00002020200002020200022222200222200020022022220000
020220020200202022022020200002000200220220002200
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X Chromosome

• Bull
• 202220200002022220002020222020202
• Cow
• 1201201212222010111022210210212022

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Data and evaluation flow
AI organizations, breed associations
samples
nominations
evaluations
Animal Improvement Programs Laboratory, USDA
Dairy producers
samples
samples
genotypes
DNA laboratories
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Adjustment of Cow Evaluations

• Traditional cow evaluations inflated compared to
  bull evaluations
• US industry wanted cows own performance to
  influence genomic evaluations. Most countries use
  only bull evaluations for SNP effect estimation
• Information from genotyped cows did not
  increasing reliability of yield traits
• Cow contributions adjusted to be comparable to
  those from bulls

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Holstein prediction accuracy
Traita Biasb b REL () REL gain ()
Milk (kg) -4.0 0.91 67.5 29.4
Fat (kg) -0.9 0.96 73.1 35.0
Protein (kg) 0.6 0.88 63.7 25.6
Fat () 0.0 1.02 85.7 47.6
Protein () 0.0 0.90 77.9 39.8
PL (months) -1.5 1.04 64.2 33.2
SCS 0.0 0.88 60.4 26.5
DPR () -0.2 1.08 46.8 17.0
Sire CE 1.0 0.79 40.9 13.8
Daughter CE -1.0 0.93 44.3 18.1
Sire SB 2.1 0.87 29.8 7.2
Daughter SB 0.3 0.89 29.3 2.7
a CE calving ease and SB stillbirth. b 2010
deregressed value 2006 genomic evaluation.
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Reliabilities for young bulls
GPTA
Traditional PA
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Holstein Protein SNP Effects
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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

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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)

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Updates between trad. evaluations

• Genomic evaluations calculated every month
• Evaluations not released for animals that already
  have an official evaluation
• Evaluations of new animals distributed to owners
• Females by breed associations
• Males by NAAB

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Impact on producers

• Young-bull evaluations with accuracy of early
  1stcrop 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
• European collaboration to share genotypes
• Large number of predictor animals increases
  prediction accuracy
• Importing countries changing rules to allow for
  genomically evaluated young bulls

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Future
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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

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Application to more traits

• Animals 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?

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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

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