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Outline
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How the genomic evaluation program works
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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
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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
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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
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SNP edits and counts
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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
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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
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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
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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 )
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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
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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
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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
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Data & evaluation flow
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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
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Genomic vs. traditional (cont.)
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Genomic vs. traditional – protein PTA
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Genomic vs. traditional – net merit
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Genomic vs. trad. – protein reliability
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Genomic vs. trad. – net merit reliability
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Reliability frequencies – young bulls
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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
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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
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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
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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
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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
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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
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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
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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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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
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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
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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
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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
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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
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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
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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)
  • Agricultural Research Service, USDA