Producer Uptake: How might genomic information be translated to industry outcomes? Alison Van Eenennaam, Ph.D.

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1 Producer Uptake: How might genomic information be translated to industry outcomes? Alison Van Eenennaam, Ph.D. Cooperative Extension Specialist Animal Biotechnology and Genomics Department of Animal Science University of California, Davis US Bovine Respiratory Disease Coordinated Agricultural Project The Integrated Program for Reducing Bovine Respiratory Disease Complex (BRDC) in Beef and Dairy Cattle Coordinated Agricultural Project is supported by Agriculture and Food Research Initiative Competitive Grant no from the USDA National Institute of Food and Agriculture. AABP 9/18/2015

2 Overview Overview of genomic selection Dairy Beef Incorporating BRD into genetic evaluations Approach will likely depend upon the genetic architecture of trait If many loci (polygenic effect) then use genomic prediction If few large effect loci then may be able to use genotype calls directly to get reasonably accurate genetic merit estimates Inclusion of BRD in economic selection indexes using appropriate weighting

3 The sequencing of the bovine genome allowed for the discovery of many SNP markers High-throughput genotyping technology enabled the development of 50K SNP chip in 2009 Matukumalli LK, Lawley CT, Schnabel RD. et al. Development and characterization of a high density SNP genotyping assay for cattle. PLoS One. 2009;4:e5350

4 Phenotypes Van Eenennaam et al Annu. Rev. Anim. Biosci. 2:

5 Records in dairy database Pedigree records 71,974,045 Animal genotypes 1,035,590 Lactation records (since 1960) 132,629,200 Daily yield records (since 1990) 641,864,015 Reproduction event records 179,559,035 Calving difficulty scores 29,528,607 Stillbirth scores 19,567,198 Data from George Wiggins, USDA ARS (7/2015)

6 Dairy genetic merit calculation schedule Triannual genetic merit estimates from processed phenotypic data Monthly genomic evaluations based on estimates of marker effects using genotypic data and triannual phenotype-based evaluations Weekly evaluations using marker effect estimates from monthly evaluations Data from George Wiggins, USDA ARS (7/2015)

7 Traits included History of the USDA economic indexes for dairy cattle USDA genetic-economic index (and year introduced) PD$ (1971) MFP$ (1976) CY$ (1984) NM$ (1994) NM$ (2000) NM$ (2003) NM$ (2006) NM$ (2010) NM$ (2014) Milk Fat Protein Productive life Somatic cell score Udder composite Feet/legs composite Body size composite Daughter pregnancy rate Cow conception rate 2 Heifer conception rate 1 Calving ability $index

8 Average net merit ($) Average gain: $19.42/year Rate of genetic gain in marketed Holstein bulls has doubled Average gain: $47.95/year Average gain: $87.49/year Year entered AI Data from George Wiggins, USDA ARS (7/2015)

9 Dairy industry ideally suited to increasing rate of genetic gain ( G/year) using genomic selection Mostly one breed High use of AI Clear selection goal (NM$) Large number of high accuracy A.I. sires for training Extensive, uniform collection of data on traits Central evaluation (AIPL) receiving genotypes Obvious way to decrease age of selection in sires AI companies funding the genotyping because they get a clear cost savings in terms of young sire program and decrease generation interval Gx2

10 The Beef Cattle Industry Little use of AI Relatively few high accuracy sires for training Multiple competing selection goals cow/calf, feedlot, processor little data sharing between sectors Few/no records on many economically-relevant traits Many breeds, some small with limited resources Crossbreeding is important No centralized national cattle evaluation Not clear who should pay for testing breeders? Breed associations? public funds?

11 Genotypes in American Angus Association database Date Genotypes Oct ,000 Oct ,000 Oct ,000 Current 153,000 Adding approximately 1,500 genotypic records a week = 78,000 per year Slide provided courtesy of Dan Moser, president of Angus Genetics Inc. (AGI) and Association director of performance programs

12 Increase in genotypic data available for American Angus Association calibrations Number of animals with 50K genotypes 70,000 60,000 50,000 40,000 30,000 20,000 10, ,550 38,988 11,756 2,253 Y_2010 (Calibration 1) Y_2012 (Calibration 2) Y_2013 (Calibration 3) Y_2014 (Calibration 4) Slide provided courtesy of Dan Moser

13 %GV (genetic variation) that is explained within a common validation data set using the marker effects estimated from the different calibrations %GV_2010 %GV_2012 %GV_2013 %GV_ Data provided by Dr. Prashanth Boddhireddy, Zoetis

14 Genetic correlation between genomic prediction results and phenotypic AAA data by trait (9/2014) Trait Genetic Correlation (r) % Genetic Variation Progeny Equivalent Calving Ease Direct Birth Weight Weaning Weight Yearling Weight Milk Yearling Height Yearling Scrotal Dry Matter Intake Docility Heifer Pregnancy Mature Weight Carcass Weight Carcass Marbling Carcass Rib Carcass Fat Slide provided courtesy of Dan Moser

15 Information sources for EPDs DNA just one source of data for GE-EPD r r Accuracy (r) correlation between test result and actual genetic merit

16 Potential benefits of genomics are greatest for economically-important traits that: Are difficult or expensive to measure Cannot be measured until late in life or after the animal is dead Are not currently selected for because they are not routinely measured so we have no records to train prediction equations Have low heritability Yep, looks like all of em were susceptible

17 No one said we are targeting the low hanging fruit Disease Reproduction Feed Efficiency Production Traits

18 However, BRDC resistance would be a very valuable target The presence of genetic variation in resistance to disease, coupled with the increased consumer pressure against the use of drugs, is making genetic solutions to animal health problems increasingly attractive. Even if the markers predict only 20% of the genetic variation for this trait, this is likely to be valuable information given the significant economic costs associated with BRD. This would provide a selection criterion where now we have none. Newman, S. and Ponzoni, R.W Experience with economic weights. Proc. 5 th World Congress on Genetics Applied to Livestock Production. 18:

19 Incorporating of BRD into genetic evaluations Approach will likely depend upon the genetic architecture of trait If many loci (polygenic effect) then use genomic predictions as with other traits but will require ongoing phenotyping of genotyped animals to recalibrate marker effects If there are a few large effect loci (oligogenic) then may be able to use SNP calls directly to get reasonably accurate genetic merit estimates

20 BRD phenotypes are not currently routinely recorded on farm mtools/8calf/calf_health_scoring_chart.pdf scoringsystem.pdf.

21 Genomic selection for producer-recorded health event data in US dairy cattle Computer records for disease conditions used to develop genomic selection approaches for common health events: cystic ovaries (CYST), displaced abomasum (DSAB), ketosis (KETO), lameness (LAME), mastitis (MAST), metritis (METR) retained placenta (RETP). 134,226 total first-parity records,174,069 total records from parities 2 through 5 for 100,635 cows Parker Gaddis KL, et al Genomic selection for producer-recorded health event data in US dairy cattle. J Dairy Sci May;97(5):

22 Increase in reliability from genomic information ~ 0.12 Parker Gaddis KL, et al Genomic selection for producer-recorded health event data in US dairy cattle. J Dairy Sci May;97(5):

23 The importance of recording health traits To be successful, there needs to be a balance between the effort required to collect these health data and subsequent benefits. Electronic systems that make such data capture easy and automated are likely key to the long-term success. The authors concluded that The development of genomic selection methodologies, with accompanying substantial gains in reliability for lowheritability traits, may dramatically improve the feasibility of genetic improvement of dairy cow health. Parker Gaddis KL, et al Genomic selection for producer-recorded health event data in US dairy cattle. J Dairy Sci May;97(5):

24 Attempt to identify functional SNP variants (i.e. actual causative mutations) whose effects are likely to persist across generations and possibly even breeds Georges M. Towards sequence-based genomic selection of cattle. Nat Genet 2014;46:

25 Development of a functional variant SNP chip assay The University of Missouri (Dr. Jerry Taylor et al.), in collaboration with GeneSeek, have developed an Illumina 250K functional variant assay. The assay was designed using sequence data on over 400 individuals from multiple taurine breeds and sequence data from the 1000 Bull Genomes Project. The chip is focused on the detection of genetic variants (199K) likely to functional in taurine cattle. The assay will be used to genotype samples from the BRD CAP this November. Jerry Taylor, Personal comm. 9/2015

26 Incorporation of BRD into dairy genetic evaluations Estimate how much of the genetic variation in BRD susceptability is explained by markers/prediction equation Incorporate BRD susceptability with the appropriate economic weighting into the Net Merit index ($NM) Include SNP markers as appropriate in future SNP chips so that BRD relevant information seemlessly flows into national dairy cattle genetic evaluations If there are large effect causative (functional) mutations then their effect should persist across generations Otherwise will need to recalibrate prediction equations using BRD phenotyping of newly genotyped animals

27 Incorporation of BRD into beef breed genetic evaluations If there are large effect causative (functional) mutations then their effect should persist across breeds Otherwise will need to develop prediction equations for all breed and develop ongoing phenotyping program Need to develop a standardized set of practical guidelines for BRD scoring that could be used in industry herds with the data to be used for genetic evaluation phenotyping effort cannot be greater than subsequent benefit Need to incorporate BRD susceptability with the appropriate weighting into breed economic indexes Selection against BRD susceptability may not have value to the cow calf producer so need to incentivize the inclusion of selection for this trait in indexes

28 Some industries have successfully targeted selection for disease In dairy cattle, selection programs have been developed to take advantage of genetic variability in mastitis resistance, despite the fact that the heritability of clinical mastitis is low and mastitis resistance has an adverse correlation with production traits Chicken breeders have long used breeding to improve resistance to avian lymphoid leucosis complex and Marek s disease A large major effect locus for swine porcine reproductive and respiratory syndrome (PRRS) has been identified Stear, M. J., S. C. Bishop, B. A. Mallard, and H. Raadsma The sustainability, feasibility and desirability of breeding livestock for disease resistance. Res Vet Sci 71: 1-7

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30 Questions? *Cough* The Integrated Program for Reducing Bovine Respiratory Disease Complex (BRDC) in Beef and Dairy Cattle Coordinated Agricultural Project is supported by Agriculture and Food Research Initiative Competitive Grant no from the USDA National Institute of Food and Agriculture.