G.R. Wiggans Animal Improvement Programs Laboratory Agricultural Research Service, USDA Beltsville, MD 2009 G.R. WiggansGenomics: Emerging Markets Program (1) How the genomic evaluation program works

G.R. Wiggans 2009 Genomics: Emerging Markets Program (2) Short history l Illumina BovineSNP50™ BeadChip developed l Accuracy of genomic information assessed by using 2004 evaluations of bulls born before 2000 to predict 2009 evaluations of young bulls l Unofficial genomic evaluations of bull calves provided to industry beginning in April 2008 l Jersey results released in October 2008 l New results released every 2 months l Nearly 23,000 animals genotyped through Mar. 2009

G.R. Wiggans 2009 Genomics: Emerging Markets Program (3) What is a SNP? l Single-nucleotide polymorphism l Place on the chromosome where animals differ in the nucleotides (A, C, T, or G) they have l Usually not part of the gene that controls a trait – quantitative trait locus (QTL) l With enough SNPs, association between SNP alleles and QTL alleles gives useful evaluations l SNPs chosen to be distributed evenly and have both alleles well represented in population

G.R. Wiggans 2009 Genomics: Emerging Markets Program (4) Source of genomic evaluations l DNA extracted from blood, hair, or semen l ~40,000 genetic markers (SNPs) evaluated l For each SNP, difference in PTA estimated between animals with 1 allele compared to the other allele l Genomic evaluation combines SNP effect estimates with existing PA or PTA l Genomic data contribute ~11 daughter equivalents to reliability

G.R. Wiggans 2009 Genomics: Emerging Markets Program (5) SNP edits and counts Illumina SNP50 BeadChip58,336 Insufficient number of beads1,389 Unscorable SNP4,360 Monomorphic in Holsteins5,734 Minor allele frequency <5%6,145 Not in H-W equilibrium282 Highly correlated2,010 Used for genomic prediction38,416

G.R. Wiggans 2009 Genomics: Emerging Markets Program (6) How to get animals genotyped l Participating AI organizations have 5-year exclusive right to evaluate bulls genomically l Each AI organization genotypes first-choice flushes, thereby usually avoiding duplicate genotypes l Web-based system collects nominations w Avoid duplication w Confirm validity of ID and pedigree w Associate sample ID with animal ID l Breed associations offer cow genotyping service

G.R. Wiggans 2009 Genomics: Emerging Markets Program (7) Steps to prepare genotypes l Nominate animal for genotyping; confirm not already genotyped l Collect hair, blood, or semen from animal w Blood not suitable for twins l Send to laboratory for extraction l Transfer DNA to BeadChip (12 samples/chip) for 3-day genotyping process

G.R. Wiggans 2009 Genomics: Emerging Markets Program (8) Steps to prepare genotypes (cont.) l Read red/green intensities from chip l Transfer intensity files to AIPL for calling genotypes l Check genotypes for duplicates, parent- progeny conflicts, and wrong sex

G.R. Wiggans 2009 Genomics: Emerging Markets Program (9) DNA laboratories l Research w Bovine Functional Genomics Laboratory (BFGL), USDA (Beltsville, MD) w University of Alberta (Edmonton, AB, Canada) w University of Missouri (Columbia, MO) w Illumina (San Diego, CA) l Commercial (some do extraction only) w GeneSeek (Lincoln, NE) w Genetics & IVF Institute (Fairfax, VA) w Genetic Visions (Middleton, WI) w DNA LandMarks (Saint-Jean-sur-Richelieu, QC, Canada) w Maxxam Analytics (Mississauga, ON, Canada) w ABS (DeForest, WI, through SyGen/PIC, Franklin, KY )

G.R. Wiggans 2009 Genomics: Emerging Markets Program (10) What can go wrong l Sample doesn’t provide adequate DNA quality or quantity l Genotype has many SNPs that can’t be determined (90% call rate required) l Genotype conflicts with parent(s) w Pedigree error w Sample ID error w Laboratory error w Genotype checked against all others to find true parent

G.R. Wiggans 2009 Genomics: Emerging Markets Program (11) Accurate evaluations l Accurate genomic evaluations require estimates of SNP effects l Evaluations with high reliability provide the most information l Recent animals are more useful than ones from earlier generations l Reliability of genomic evaluations increases with number of predictor animals

G.R. Wiggans 2009 Genomics: Emerging Markets Program (12) Genomic evaluation & reliability l Calculate parent average (PA) based only on genotyped animals with best linear unbiased prediction l Combine traditional PA (or evaluation) with genomic PA and evaluation using selection index weights l Update traditional evaluation with additional information from genomics l Reliability from inverse of genomic relationship matrix

G.R. Wiggans 2009 Genomics: Emerging Markets Program (13) Data & evaluation flow Animal Improvement Programs Laboratory, USDA AI organizations, breed associations Dairy producers DNA laboratories samples evaluations genotypes nominations evaluations

G.R. Wiggans 2009 Genomics: Emerging Markets Program (14) Genomic vs. traditional PTA l Genotype can be thought of as source of information like parents, progeny, and records l Official PTA that include a genomic contribution are identified l One genotype used to calculate genomic evaluations for all 29 traits l Genomic evaluations used the same as traditional PTA l Expected to increase rate of genetic improvement because of a large decrease in generation interval

G.R. Wiggans 2009 Genomics: Emerging Markets Program (15) Genomic vs. traditional (cont.) l Protein l Net merit Bull birth yearEvaluationSDMin.Max.Corr. 1995–2004Genomic PTA158– Traditional PTA159– –2008Genomic PTA152– Traditional PA126– Bull birth yearEvaluationSDMin.Max.Corr. 1995–2004Genomic PTA17– Traditional PTA17– –2008Genomic PTA16– Traditional PA12–27 79

G.R. Wiggans 2009 Genomics: Emerging Markets Program (16) Genomic vs. traditional – protein PTA

G.R. Wiggans 2009 Genomics: Emerging Markets Program (17) Genomic vs. traditional – net merit

G.R. Wiggans 2009 Genomics: Emerging Markets Program (18) Genomic vs. trad. – protein reliability

G.R. Wiggans 2009 Genomics: Emerging Markets Program (19) Genomic vs. trad. – net merit reliability

G.R. Wiggans 2009 Genomics: Emerging Markets Program (20) Reliability frequencies – young bulls Genomic PTA Traditional PA

G.R. Wiggans 2009 Genomics: Emerging Markets Program (21) Collaboration with Canada l Semex w Participated since beginning of genomics research w Contributed genotypes to providing a important increase in accuracy for first test l Genotypes will be shared between AIPL and Canadian Dairy Network l AIPL and University of Guelph collaboration

G.R. Wiggans 2009 Genomics: Emerging Markets Program (22) Collaboration with Canada (cont.) l Same set of predictor animals used in Canada and U.S. so that evaluations of genotyped animals have same accuracy l Canada expects official release of genomic evaluations in August 2009 l Common procedures between 2 countries assist in industry acceptance

G.R. Wiggans 2009 Genomics: Emerging Markets Program (23) Use of genomic evaluations l AI organizations determine which young bulls to buy l Considered in selection of mating sires l Impact on bull dam selection will increase l Used to market semen from 2-year-old bulls

G.R. Wiggans 2009 Genomics: Emerging Markets Program (24) January 2009 l Genomic evaluations became official l Genotyped ancestors contribute their evaluations to descendants l Evaluations of all genotyped females are public l Evaluations of males enrolled with NAAB or ≥24 months old are public l Young-bull genomic evaluations may be shared among AI organizations or disclosed by owner

G.R. Wiggans 2009 Genomics: Emerging Markets Program (25) Updates between official evaluations l Genomic evaluations calculated approximately every 2 months l Evaluations of animals that already have an official evaluation not released l Evaluations of new animals distributed to owners w Females by breed associations w Males by NAAB l Usually 1,000–2,000 new genotypes included

G.R. Wiggans 2009 Genomics: Emerging Markets Program (26) Distribution of evaluations l Nomination establishes a requester who receives the genomic evaluation l Requesters w 7 participating AI organizations w U.S. and Canadian Holstein associations w American Jersey Cattle Association w Some laboratories l Requesting AI organization can agree to share an evaluation with other AI organizations

G.R. Wiggans 2009 Genomics: Emerging Markets Program (27) Distribution of evaluations (cont.) l Evaluations of all females sent to respective breed associations for distribution to owners l NAAB distributes bull evaluations to owners and manages sharing of evaluations among AI organizations l Genomic evaluations of animals with official evaluations released as unofficial at updates between official evaluations

G.R. Wiggans 2009 Genomics: Emerging Markets Program (28) Impact on producers l Young-bull evaluations with accuracy of early 1st-crop evaluations l AI organizations marketing genomically evaluated 2-year-olds l Bull dams likely to be required to be genotyped l Rate of genetic improvement likely to increase by up to 50% l Progeny-test programs changing

G.R. Wiggans 2009 Genomics: Emerging Markets Program (29) Schedule l Calculate SNP effects with each of 3 annual traditional evaluations l Calculate genomic evaluations once or more between traditional evaluations w Recalculate SNP effects if significant number of predictor animals added w May use existing SNP effects if only young animals added

G.R. Wiggans 2009 Genomics: Emerging Markets Program (30) Improvements l Require bar codes on sample containers to reduce errors and improve lab efficiency l Require animals be enrolled with breed association before DNA sample collected l Process genotypes frequently; check for and report conflicts as received l Reduce processing time by improving efficiency of genotype calling either by laboratories or at AIPL

G.R. Wiggans 2009 Genomics: Emerging Markets Program (31) Calling genotypes l Scanner reads chip recording intensities of red and green l Software converts those to AA, AB, or BB w Genotype is missing if assignment is uncertain l Accuracy can be improved by adjusting for variation in intensity due to SNP and animal l Techniques to automate adjustment are underway l Manual intervention can increase accuracy of calling with current software

G.R. Wiggans 2009 Genomics: Emerging Markets Program (32) Plans to increase accuracy l Genotype more predictor bulls w Automatic increase as bulls in waiting receive traditional evaluations l Increase number of SNPs used l Reach 1,500 Brown Swiss through foreign collaboration? l Increase genotyped Jerseys from both domestic animals and possible foreign collaboration

G.R. Wiggans 2009 Genomics: Emerging Markets Program (33) International implications l All major dairy countries investigating genomic selection l Interbull meeting January 2009 discussed how genomic evaluations should be integrated l AI organizations need to find balance between competitive benefits from treating genotypes as proprietary versus sharing l Importing countries must change rules to allow for genomically evaluated young bulls

G.R. Wiggans 2009 Genomics: Emerging Markets Program (34) Longer-term possibilities l Determine inheritance of individual chromosome segments (haplotyping) w May allow better tracking of QTL l Approximate genotypes of missing ancestors to increase predictor population l Increase number of SNPs or even use entire DNA sequence

G.R. Wiggans 2009 Genomics: Emerging Markets Program (35) Implications l Extraordinarily rapid implementation of genomic evaluations l Young bull acquisition and marketing now based on genomic evaluations l Genomic evaluations may allow more cows from commercial herds to be used as bull dams

G.R. Wiggans 2009 Genomics: Emerging Markets Program (36) Financial support l National Research Initiative grants, USDA l NAAB (Columbia, MO) w ABS Global (DeForest, WI) w Accelerated Genetics (Baraboo, WI) w Alta (Balzac, AB) w Genex (Shawano, WI) w New Generation Genetics (Fort Atkinson, WI) w Select Sires (Plain City, OH) w Semex Alliance (Guelph, ON) w Taurus-Service (Mehoopany, PA) l Holstein Association USA (Brattleboro, VT) l American Jersey Cattle Association (Reynoldsburg, OH) l Agricultural Research Service, USDA