WiggansBritish Cattle Conference 2015 (1) Dr. George R. Wiggans Animal Genomics and Improvement Laboratory Agricultural Research Service, USDA Beltsville,

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Presentation transcript:

WiggansBritish Cattle Conference 2015 (1) Dr. George R. Wiggans Animal Genomics and Improvement Laboratory Agricultural Research Service, USDA Beltsville, MD (voice) (fax) Genomics and where it can take us

WiggansBritish Cattle Conference 2015 (2) Genomics and SNP l Genomics – Applies DNA technology and bioinformatics to sequence, assemble and analyze the function and structure of genomes l SNP – Single nucleotide polymorphisms; serve as markers to track inheritance of chromosomal segments l Genomic selection – Selection using genomic predictions of economic merit early in life

WiggansBritish Cattle Conference 2015 (3) 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

WiggansBritish Cattle Conference 2015 (4) US genomic evaluation system

WiggansBritish Cattle Conference 2015 (5) 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 Animal Genomics and Improvement Lab (AGIL) responsible for research and development to improve the evaluation system l CDCB and AGIL employees co-located in Beltsville Dr. João Dürr is CDCB CEO

WiggansBritish Cattle Conference 2015 (6) Funding l CDCB evaluation calculation and dissemination funded by fee system w Based on animals genotyped w 87% of revenue from bulls w Higher fees for herds that contribute less information l USDA research on evaluation methodology funded by US Federal Government $

WiggansBritish Cattle Conference 2015 (7) Council on Dairy Cattle Breeding l 3 members from each organization l Total of 12 voting members l 2 nonvoting industry members Purebred Dairy Cattle Association National Association of Animal Breeders Dairy Records Processing Centers Dairy Herd Information

WiggansBritish Cattle Conference 2015 (8) Genomic data flow DNA samples genotypes genomic evaluations nominations, pedigree data genotype quality reports genomic evaluations DNA samples genotypes DNA samples Dairy Herd Information (DHI) producer Council on Dairy Cattle Breeding (CDCB) DNA laboratory AI organization, breed association AI organization, breed association

WiggansBritish Cattle Conference 2015 (9) History of genomic evaluations l BovineSNP50 BeadChip availableDec l First unofficial evaluation releasedApr l Official evaluations for Holsteins and JerseysJan l Official evaluations for Brown SwissAug l Monthly evaluation Jan l Official 3K evaluationsDec l BovineLD BeadChip availableSept l Official evaluations for Ayrshires Apr l Weekly evaluation Nov. 2014

WiggansBritish Cattle Conference 2015 (10) Evaluation flow l Animal nominated for genomic evaluation by approved nominator l DNA source sent to genotyping lab (2014)  SourceSamples (no.)Samples (%) Blood 10,7274 Hair113,45539 Nasal swab2,9541 Semen3,4321 Tissue149,30151 Unknown12,3014

WiggansBritish Cattle Conference 2015 (11) Evaluation flow (continued) l DNA extracted and placed on chip for 3-day genotyping process l Genotypes sent from genotyping lab to CDCB for accuracy review  

WiggansBritish Cattle Conference 2015 (12) 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 SNP indicates genotype quality l Target of <10 SNP in each category

WiggansBritish Cattle Conference 2015 (13) Before clustering adjustment 86% call rate

WiggansBritish Cattle Conference 2015 (14) After clustering adjustment 100% call rate

WiggansBritish Cattle Conference 2015 (15) 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 61K l SNP effects estimated l Final evaluations calculated       

WiggansBritish Cattle Conference 2015 (16) Evaluation flow (continued) l Evaluations released to dairy industry w Download from CDCB FTP site with separate files for each nominator w Weekly release of evaluations of new animals w Monthly release for females and bulls not marketed w All genomic evaluations updated 3 times each year with traditional evaluations 

WiggansBritish Cattle Conference 2015 (17) 2014 genotypes by chip SNP density Chip SNP densityFemaleMale All animals Low 239,07129,631268,702 Medium9,09814,20223,300 High All248,309 43,861292,170

WiggansBritish Cattle Conference 2015 (18) 2014 genotypes by breed and sex BreedFemaleMale All animals Female: male Ayrshire 1, ,69488:12 Brown Swiss9448,6419,58510:90 Guernsey1, ,11084:16 Holstein212,76530,883243,64887:13 Jersey31,3233,79335,11689:11 Milking Shorthorn21367:33 Normande0100:100 Crossbred :0 All248,30943,861292,17085:15

WiggansBritish Cattle Conference 2015 (19) Growth in bull predictor population BreedJan mo gain Ayrshire Brown Swiss6, Holstein26,7592,174 Jersey4,448245

WiggansBritish Cattle Conference 2015 (20) Holstein prediction accuracy *2013 deregressed value – 2009 genomic evaluation TraitBias*Reliability (%) Reliability gain (% points) Milk (kg)− Fat (kg)− Protein (kg)− Fat (%) Protein (%) Productive life (mo)− Somatic cell score Daughter pregnancy rate (%) Sire calving ease Daughter calving ease− Sire stillbirth rate Daughter stillbirth rate

WiggansBritish Cattle Conference 2015 (21) Holstein prediction accuracy *2013 deregressed value – 2009 genomic evaluation TraitBias*Reliability (%) Reliability gain (% points) Final score Stature− Dairy form− Rump angle Rump width− Feed and legs Fore udder attachment − Rear udder height − Udder depth − Udder cleft− Front teat placement − Teat length−

WiggansBritish Cattle Conference 2015 (22) Gene tests (imputed and actual) l Bovine leucocyte adhesion deficiency (BLAD) l Complex vertebral malformation (CVM) l Deficiency of uridine monophosphate synthase (DUMPS) l Syndactyly (mulefoot) l Weaver Syndrome, spinal dismyelination (SDM), spinal muscular atrophy (SMA) l Red coat color l Polledness

WiggansBritish Cattle Conference 2015 (23) New fertility haplotype for Jerseys (JH2) l Chromosome 26 at 8.8–9.4 Mbp l Carrier frequency w 14–28% in decades before 1990 w Only 2.6% now l Estimated effect on conception rate of –4.0% ± 1.5% l Additional sequencing needed to find causative genetic variant

WiggansBritish Cattle Conference 2015 (24) Parent ages for marketed Holstein bulls

WiggansBritish Cattle Conference 2015 (25) Inbreeding for Holstein cows – Inbreeding – Expected future inbreeding

WiggansBritish Cattle Conference 2015 (26) Active AI bulls that were genomic bulls

WiggansBritish Cattle Conference 2015 (27) Genetic merit of marketed Holstein bulls Average gain: $19.42/year Average gain: $47.95/year Average gain: $87.49/year

WiggansBritish Cattle Conference 2015 (28) Stability of genomic evaluations l 642 Holstein bulls w Dec NM$ compared with Dec NM$ w First traditional evaluation in Aug w  50 daughters by Dec l Top 100 bulls in 2012 w Average rank change of 9.6 w Maximum drop of 119 w Maximum rise of 56 l All 642 bulls w Correlation of 0.94 between 2012 and 2014 w Regression of 0.92

WiggansBritish Cattle Conference 2015 (29) Improving accuracy l Increase size of predictor population w Share genotypes across country w Include females l Use more or better SNP l Account for effect of genomic selection on traditional evaluations l Reduce cost to reach more selection candidates

WiggansBritish Cattle Conference 2015 (30) New GHD version (in development) l Around 140K SNP expected l Include 16,248 among 60,671 SNP currently used that are not on GHD l Many added SNP have low to moderate MAF w Research underway to determine if they improve evaluation accuracy

WiggansBritish Cattle Conference 2015 (31) Mating programs l Match genotypes of parents to minimize genomic inbreeding l Avoid mating carriers l Consider nonadditive gene action l May attempt to increases variance to get outliers

WiggansBritish Cattle Conference 2015 (32) Future l Discovery of causative genetic variants w Do not have linkage decay w Added to chips as discovered w Used when enough genotypes exist to support imputation w Accelerated by availability of sequence data at a lower cost l Evaluation of benefit from larger SNP sets as cost per SNP genotype declines l Application of genomics to more traits l Across-breed evaluation l Accounting for genomic pre-selection

WiggansBritish Cattle Conference 2015 (33) Conclusions l Genomic evaluation has dramatically changed dairy cattle breeding l Rate of gain has increased primarily because of large reduction in generation interval l Genomic research is ongoing w Detect causative genetic variants w Find more haplotypes that affect fertility w Improve accuracy

WiggansBritish Cattle Conference 2015 (34) Questions? Holstein and Jersey crossbreds graze on American Farm Land Trust’s Cove Mountain Farm in south-central Pennsylvania Source: ARS Image Gallery, image #K ; photo by Bob Nichols