1. 2014 John B. Cole Animal Genomics and Improvement Laboratory Agricultural Research Service, USDA Beltsville, MD john.cole@ars.usda.gov Genetic improvement programs for US dairy cattle

2. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (2) Cole U.S. dairy population and milk yield

3. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (3) Cole U.S. DHI dairy statistics (2011) l 9.1 million U.S. cows l ~75% bred AI l 47% milk recorded through Dairy Herd Information (DHI) w 4.4 million cows − 86% Holstein − 8% crossbred − 5% Jersey − <1% Ayrshire, Brown Swiss, Guernsey, Milking Shorthorn, Red & White w 20,000 herds w 220 cows/herd w 10,300 kg/cow

4. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (4) Cole Collaboration with industry l Council on Dairy Cattle Breeding (CDCB) responsible for receiving data and for computing and delivering US genetic evaluations for dairy cattle l AIP responsible for research and development to improve the evaluation system l CDCB and AIP employees co-located in Beltsville Dr. Jo ão D ü rr is CDCB CEO

5. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (5) Cole Council on Dairy Cattle Breeding l 3 board members from each organization l Total of 12 voting members l 2 nonvoting industry members CDCB PDCANAABDRPCDHIA Purebred Dairy Cattle Association National Association of Animal Breeders Dairy Records Processing Centers Dairy Herd Information Association

6. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (6) Cole Genetic evaluation advances YearAdvanceGain, % 1862USDA established 1895USDA begins collecting dairy records 1926Daughter-dam comparison100 1962Herdmate comparison50 1973Records in progress10 1974Modified contemporary comparison5 1977Protein evaluated4 1989Animal model4 1994Net merit, productive life, and somatic cell score 50 2008Genomic selection>50

7. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (7) Cole Animal model l 1989 to present l Introduced by Wiggans and VanRaden l Advantages w Information from all relatives w Adjustment for genetic merit of mates w Uniform procedures for males and females w Best prediction (BLUP) w Crossbreds included (2007) w Genomic information added (2008)

8. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (8) Cole Traits evaluated YearTraitYearTrait 1926Milk & fat yields2000Calving ease 1 1978Conformation (type)2003Daughter pregnancy rate 1978Protein yield2006Stillbirth rate 1994Productive life2006Bull conception rate 2 1994Somatic cell score (mastitis) 2009Cow and heifer conception rates 1 Sire calving ease evaluated by Iowa State University (1978–99) 2 Estimated relative conception rate evaluated by DRMS in Raleigh, NC (1986–2005)

9. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (9) Cole Evaluation methods for traits l Animal model (linear) w Yield (milk, fat, protein) w Type (AY, BS, GU, JE) w Productive life w Somatic cell score w Daughter pregnancy rate w Heifer conception rate w Cow conception rate l Sire–maternal grandsire model (threshold) w Service sire calving ease w Daughter calving ease w Service sire stillbirth rate w Daughter stillbirth rate Heritability 8.6% 3.6% 3.0% 6.5% 25 – 40% 7 – 54% 8.5% 12% 4% 1% 1.6%

10. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (10) Cole Type traits l Stature l Strength l Body depth l Dairy form l Rump angle l Thurl width l Rear legs (side) l Rear legs (rear) l Foot angle l Feet and legs score l Fore udder attachment l Rear udder height l Rear udder width l Udder cleft l Udder depth l Front teat placement l Rear teat placement l Teat length

11. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (11) Cole Holstein milk (kg) Phenotypic base = 11,828 kg Cows Sires 79 kg/yr

12. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (12) Cole Holstein productive life (mo) Phenotypic base = 27.2 mo Sires Cows 0.2 mo/yr

13. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (13) Cole Holstein somatic cell score (log 2 ) Sires Cows 0.02/yr Phenotypic base = 3.0

14. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (14) Cole Holstein daughter pregnancy rate (%) Phenotypic base = 22.6% Sires Cows  0.1%/yr

15. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (15) Cole Holstein calving ease (%) Daughte r Service-sire phenotypic base = 7.9% Daughter phenotypic base = 7.5% Service sire 0.18%/yr 0.01%/yr

16. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (16) Cole Trait Relative value (%) Net merit Cheese merit Fluid merit Milk (lb)0–1519 Fat (lb)191320 Protein (lb)16250 Productive life (PL, mo)221522 Somatic cell score (SCS, log 2 )–10–9–5 Udder composite (UC)757 Feet/legs composite (FLC)434 Body size composite (BSC)–6–4–6 Daughter pregnancy rate (DPR, %)11812 Calving ability (CA$, $)535 Genetic-economic indices (2010)

17. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (17) Cole Trait Relative emphasis on traits in index (%) PD$ 1971 MFP$ 1976 CY$ 1984 NM$ 1994 NM$ 2000 NM$ 2003 NM$ 2006 NM$ 2010 Milk5227–265000 Fat4846452521222319 Protein…27534336332316 PL………2014111722 SCS………–6–9 –10 UDC…………7767 FLC…………4434 BDC…………–4–3–4–6 DPR……………7911 SCE……………–2…… DCE……………–2…… CA$………………65 Index changes

18. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (18) Cole Traditional evaluation summary l Evaluation procedures have improved l Fitness traits have been added l Effective selection has produced substantial annual genetic improvement l Indices enable selection for overall economic merit l Fertility evaluations prevent continued decline

19. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (19) Cole Genomic evaluation system l Provides timely evaluations of young bulls for purchasing decisions l Increases accuracy of evaluations of bull dams l Assists in selection of service sires, particularly for low-reliability traits l High demand for semen from genomically evaluated 2-year-old bulls

20. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (20) Cole Genomic data flow DNA samples genotypes genomic evaluations nominations, pedigree data genotype quality reports genomic evaluations DNA samples genotypes DNA samples Dairy Herd Improvement (DHI) producer Council on Dairy Cattle Breeding (CDCB) DNA laboratory AI organization, breed association AI organization, breed association

21. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (21) Cole Progression of chips 200820092010 Official 3K evaluations Dec Unofficial 3K evaluations Sep Bovine3K BeadChip (3K) Jul BovineHD BeadChip (777K) Jan Official 50K Brown Swiss evaluations Aug Official 50K Holstein & Jersey evaluations Jan Unofficial 50K evaluations Apr BovineSNP50 BeadChip (50K) Jan 201120122013 Official 12K evaluations Oct Zoetis LD BeadChip (12K) Sep GGP v2 BeadChip (19K) May Official 19K evaluations May Official 77K evaluations Jan GGP HD BeadChip (77K) Dec Official 8K evaluations Mar GeneSeek Genomic Profiler (GGP) BeadChip (8K) Feb Official 7K & 648K evaluations Dec BovineLD BeadChip (7K) Sep Official 777K evaluations Aug Affymetrix BOS 1 Plate Array (648K) Jan

22. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (22) Cole Evaluation flow l Animal nominated for genomic evaluation by breed association or AI organization l Hair or other DNA source sent to genotyping lab l DNA extracted and placed on chip for 3-day genotyping process l Genotypes sent from genotyping lab to AIPL for accuracy review

23. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (23) Cole Laboratory quality control l Each SNP evaluated for w Call rate w Portion heterozygous w Parent-progeny conflicts l Clustering investigated if SNP exceeds limits l Number of failing SNPs indicates genotype quality l Target of <10 SNPs in each category

24. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (24) Cole Evaluation flow (continued) l Genotype calls modified as necessary l Genotypes loaded into database l Nominators receive reports of parentage and other conflicts l Pedigree or animal assignments corrected l Genotypes extracted and imputed to 45K l SNP effects estimated

25. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (25) Cole Imputation l Based on splitting genotype into individual chromosomes (maternal and paternal contributions) l Missing SNPs assigned by tracking inheritance from ancestors and descendants l Imputed dams increase predictor population l Genotypes from all chips merged by imputing SNPs not present

26. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (26) Cole findhap l Developed by Dr. Paul VanRaden, ARS, USDA l Divides chromosomes into segments l Allows for successively shorter segments (usually 3 runs) w Long segments lock in identical by descent w Shorter segments fill in missing SNPs l Separates genotype into maternal and paternal contribution, haplotypes (phasing) l Builds haplotype library sequenced by frequency

27. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (27) Cole Evaluation flow (continued) l Final evaluations calculated l Evaluations released to dairy industry w Download from CDCB FTP site with separate files for each nominator w Monthly release for new animals w All genomic evaluations updated 3 times each year with traditional evaluations

28. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (28) Cole Genomic evaluation results Source: https://www.cdcb.us/Report_Data/Marker_Effects/marker_effects.cfm?Breed=HO&Trait=Net_Merit

29. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (29) Cole Information sources for evaluations l Traditional evaluations of genotyped bulls and cows used to estimate SNP effects l Combined final evaluation w Sum of SNP effects for an animal’s alleles w Polygenetic effect w Traditional evaluation l Pedigree data used and validated by genotypes

30. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (30) Cole Genotypes received since July 2013 BreedFemaleMale All animals % female Ayrshire 1,3592291,58886 Brown Swiss*8926,2537,14512 Holstein172,95631,657204,61385 Jersey**26,4344,80431,23885 All201,64142,943244,58482 *Includes >5,000 bulls added from Interbull in June 2014 **Includes 1,068 Danish bulls added in November 2013

31. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (31) Cole Genotypes evaluated 2009 2010 201120122013

32. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (32) Cole Growth in bull predictor population BreedMay 2014 12-mo gain Ayrshire 67830 Brown Swiss5,862366 Holstein25,2762,361 Jersey4,2621,391

33. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (33) Cole Reliabilities for young Holsteins* *Animals with no traditional PTA in April 2011 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 404550556065707580 Reliability for PTA protein (%) Number of animals 3K genotypes 50K genotypes

34. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (34) Cole Holstein prediction accuracy *2013 deregressed value – 2009 genomic evaluation TraitBias* Reliability (%) Reliability gain (% points) Final score0.158.822.7 Stature−0.268.530.6 Dairy form−0.271.834.5 Rump angle0.070.234.7 Rump width−0.265.028.1 Feed and legs0.244.012.8 Fore udder attachment −0.270.433.1 Rear udder height −0.159.422.2 Udder depth −0.375.337.7 Udder cleft−0.262.125.1 Front teat placement −0.269.932.6 Teat length−0.166.729.4

35. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (35) Cole Parent ages of marketed Holstein bulls

36. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (36) Cole Marketed Holstein bulls Year entered AI Traditional progeny- tested Young genotypedAll bulls 20081,7980 20091,9093372,246 20101,8273762,203 20111,4414671,908 20121,3765551,931

37. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (37) Cole Genetic merit of marketed Holstein bulls Average gain: $19.77/year Average gain: $52.00/year Average gain: $85.60/year

38. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (38) Cole 012345 Genomic prediction of progeny test Select parents, transfer embryos to recipients Calves born and DNA tested Calves born from DNA- selected parents Bull receives progeny test Reduce generation interval from 5 to 2 years

39. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (39) Cole Genetic choices l Before genomics: w Proven bulls with daughter records (PTA) w Young bulls with parent average (PA) l After genomics: w Young animals with DNA test (GPTA) w Reliability of GPTA ~70% compared to PA ~35% and PTA ~85% for Holstein NM$

40. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (40) Cole Young bulls: 2013 NM$ vs. 2010 PA

41. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (41) Cole Proven bulls: 2013 vs. 2010 NM$

42. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (42) Cole Young bulls: 2013 vs. 2010 NM$

43. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (43) Cole % genotyped mates of top young bulls Net Merit (Aug 2013 ) Percentage of mates genotyped Supersire Numero Uno S S I Robust Topaz Garrold Mogul

44. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (44) Cole Why genomics works for dairy cattle l Extensive historical data available l Well-developed genetic evaluation program l Widespread use of AI sires l Progeny-test programs l High-value animals worth the cost of genotyping l Long generation interval that can be reduced substantially by genomics

45. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (45) Cole Key issues for the dairy industry l Inbreeding and genetic diversity (including across breeds) l Sequencing, new genes, and mutations l Novel traits, resource populations (feed efficiency, health, milk properties)

46. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (46) Cole Application to more traits l Animal’s genotype good for all traits l Traditional evaluations required for accurate estimates of SNP effects l Traditional evaluations not currently available for heat tolerance or feed efficiency l Research populations could provide data for traits that are expensive to measure l Will resulting evaluations work in target population?

47. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (47) Cole Parentage validation and discovery l Parent-progeny conflicts detected w Animal checked against all other genotypes w Reported to breeds and requesters w Correct sire usually detected l Maternal grandsire (MGS) checking w SNP at a time checking w Haplotype checking more accurate l Breeds moving to accept SNPs in place of microsatellites

48. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (48) Cole Haplotypes affecting fertility l Rapid discovery of new recessive defects w Large numbers of genotyped animals w Affordable DNA sequencing l Determination of haplotype location w Significant number of homozygous animals expected, but none observed w Narrow suspect region with fine mapping w Use sequence data to find causative mutation

49. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (49) Cole Haplotypes affecting fertility *Causative mutation known Name Chromo- some Location (Mbp) Carrier frequency (%)Earliest known ancestor HH1563.2*4.5Pawnee Farm Arlinda Chief HH2194.9–96.64.6Willowholme Mark Anthony HH3895.4*4.7Glendell Arlinda Chief, Gray View Skyliner HH411.3*0.7Besne Buck HH5992.4–93.94.4Thornlea Texal Supreme JH11515.7*23.4Observer Chocolate Soldier BH1742.8–47.014.0West Lawn Stretch Improver BH21910.6–11.715.4Rancho Rustic My Design AH11765.9–66.223.6Selwood Betty’s Commander

50. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (50) Cole Haplotypes to track known recessives *Causative mutation known RecessiveHaplotype Chromo- some Tested animals (no.) Concord- ance (%) New carriers (no.) BLADHHB 1*11,78299.9314 CVMHHC 3*13,226—2,716 DUMPSHHD 1*3,242100.03 Mule footHHM15*8797.7120 HornedHHP1345—2,050 Red coat color HHR18*4,137—5,927 SDMBHD11*10894.4108 SMABHM24*56898.1111 WeaverBHW416396.332

51. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (51) Cole International dairy breeding l Genotype alliances w North America (US, Canada, UK, Italy) w Ireland, New Zealand w Netherlands, Australia w Eurogenomics (Denmark/Sweden/Finland, France, Germany, Netherlands/Belgium, Spain, Poland) l Interbull genomic multitrait across-country evaluation (GMACE)

52. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (52) Cole Impact on breeders l Haplotype and gene tests in selection and mating programs l Trend towards a small number of elite breeders that are investing heavily in genomics l About 30% of young males genotyped directly by breeders since April 2013 l Prices for top genomic heifers can be very high (e.g., $265,000 )

53. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (53) Cole Impact on dairy producers l General w Reduced generation interval w Increased rate of genetic gain w More inbreeding/homozygosity?

54. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (54) Cole Impact on dairy producers (continued) l Sires w Higher average genetic merit of available bulls w More rapid increase in genetic merit for all traits w Larger choice of bulls in terms of traits and semen price w Greater use of young bulls

55. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (55) Cole Conclusions l Genomic evaluation has dramatically changed dairy cattle breeding l Rate of gain is increasing primarily because of a large reduction in generation interval l Genomic research is ongoing w Detect causative genetic variants w Find more haplotypes affecting fertility w Improve accuracy through more SNPs, more predictor animals, and more traits

56. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (56) Cole U.S. genomic evaluation team

57. Embrapa Gado de Leite, Juiz de Fora, MG, Brasil 10 September 2014 (57) Cole Questions?