BLUP and Genomic Selection

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1 BLUP and Genomic Selection Alison Van Eenennaam Cooperative Extension Specialist Animal Biotechnology and Genomics University of California, Davis, USA Animal Genomics and Biotechnology Education

2 Overview History of genetic improvement Speeding up genetic progress: the breeders equation and the rate of genetic gain Improvements in genetic gain possible from including DNA information into genetic predictions

3 Traditional animal breeding on the basis of phenotype (appearance) can be very successful

4 However breeding based on objective performance recording has been spectacularly successful.. Average milk production per lactation of US Holstein cows has nearly doubled during the past 40 years Image from: Dekkers, J.C.M, and F. Hospital, The use of molecular genetics in the improvement of agricultural populations. Nature Reviews Genetics 3: 22-32

5 In the absence of any other information selection can only be based on appearance or reputation

6 But what you would really like to know is the future performance of his unborn calves!!

7 What if I told you these calves belonged to the bull?

8 What if I told you these were his daughters calves?

9 What if I told you this was a typical steak from his progeny?

10 Animal breeders use records of an animals own performance and that of its relatives to predict an animal s genetic merit or ESTIMATED BREEDING VALUE (EBV)

11 What is a breeding value? An animal s breeding value is an estimate of its genetic merit, half of which will be passed on to its progeny. While we will never know the exact breeding value, for performance traits it is possible to make good estimates based on performance records of the animal and its relatives. These are called Estimated Breeding Values Calculating EBVs In the calculation of EBVs, the performance of individual animals within a contemporary group is directly compared to the average of other animals in that group. A contemporary group consists of animals of the same sex and age class within a herd, run under the same management conditions and treated equally. Indirect comparisons are made between animals reared in different contemporary groups, through the use of pedigree links between the groups.

12 What is BLUP? Technically it stands for the best linear unbiased predictor.. In reality it gives you the best genetic prediction for animals where you want to do a comparison between animals on different farms - BLUP removes the bias that is associated with different locations (or fixed effects). Because BLUP takes environmental influences into account and all EBVs are expressed relative to a common base, direct comparisons can be made across farms (as long as they are linked genetically, i.e. there are common pedigree links between the groups).

13 Challenge for breeders is to identify those individuals that have the best true breeding values Records more is better Would like records before selection Need to know genetic relationship between selection criteria being measured (e.g. an ultrasound scan) and the objective traits (e.g. marbling score) Perhaps DNA information can help improve the accuracy of breeding values

14 To accelerate the rate of genetic gain breeders can manipulate the four components of the breeders equation ΔG (rate of genetic gain) = intensity of selection X accuracy of selection (r) X genetic variance in population / generation interval

15 The genome age

16 SNP (Single Nucleotide Polymorphism) A DNA sequence variation that varies sufficiently between individuals that its inheritance can be tracked through families

17 DNA tests are most valuable for traits that are low heritability (influence that genetics rather than environment has on a trait) are difficult or expensive to measure (feed efficiency) cannot be measured until after selection has occurred (carcase data) are currently not selected for due to lack of available phenotypic data (tenderness)

18 market To date DNA tests have not accounted for sufficient genetic variation to make them cost-effective

19 BREAKDOWN OF FACTORS THAT INFLUENCE FINAL PHENOTYPE DNA TEST OTHER GENES 85% 60% ENVIRONMENT 40% GENETICS (h 2 )

20 Lead Today with 50K 1. Birth weight 2. Weaning weight 3. Weaning maternal (milk) 4. Calving ease direct 5. Calving ease maternal 6. Marbling 7. Backfat thickness 8. Ribeye area 9. Carcass weight 10. Tenderness 11. Postweaning average daily gain 12. Daily feed intake 13. Feed efficiency (net feed intake) 50K SNP chip assays 50,000 STARs spread throughout genome

21 Trait h 2 Pfizer 50K HD in Angus Number of animals in training population 1 % Genetic variation (r 2 ) Company estimate (2010) 1 Australian Calibration (2010) 2 Average Daily Gain % 1-10% Net Feed Intake % 0 Dry matter intake % 4-5% Tenderness % n.d. Calving Ease (Direct) % 6% Birth weight % 12-16% Weaning Weight % 12-19% Calving ease (maternal) % 4% Milking Ability % 10-14% Carcass weight % 6-13% Backfat thickness % 14-19% Ribeye area % 10-20% Marbling score % 4-11% 1 Pfizer Animal Genetics Technical Summary. 2 Animal Genetics and Breeding Unit (AGBU) Evaluation of Pfizer Animal Genetics HD 50K MVP Calibration.

22 Dairy industry is ideally suited to genomic selection r 0 Validation: New Progeny Tested Bulls Training population THOUSANDS of genotyped bulls with high accuracy records Degree of genetic relationship between populations (ideally similar) Predicted to double the rate of genetic gain in the dairy cattle industry r 1 Application: New Sire Candidates Slide courtesy of Marc Thallman, US MARC

23 Example: How will genomic selection help estimating the breeding value of dairy sires Young sire Parent Average x Young sire Progeny Test x Young sire Genomic Selection x Birth 5 years; >>>> cost Birth; <<<< cost A S A D A S A D A S A D Mendelian Sampling? Accuracy 0.20 Mendelian Sampling Accuracy 0.80 Mendelian Sampling? Accuracy 0.65 Slide courtesy of Gonzalo Rincon, UC Davis

24 Obtaining accurate DNA tests will be difficult in beef Multiple competing selection goals producer, feedlot, processor little data sharing between sectors Relatively few sires with high accuracy records for training so often have to used records from individuals which means you need a lot of records Few/no records on many economically-relevant traits Difficult to get carcase data in appropriate contemporary groups, and associated with the correct animal Crossbreeding is important (e.g. Wagyu x Angus) DNA tests that are developed in one breed do not work well in other breeds

25 Objective Estimate the value of using DNA test information to increase the accuracy of beef bull selection in a seedstock breeding program The expected returns from using a commercial sire sourced from a seedstock herd using DNA testing Additionally, the value of marker information in the selection of replacement stud males to be mated in a seedstock breeding program was also estimated. Van Eenennaam, A. L., J.H. van der Werf, and M.E. Goddard Value of DNA information for beef bull selection. 9 th World Congress of Genetics Applied to Livestock Production. Leipzig, Germany

26 To value genetic gain need a $Index

27

28 Proportion of genetic variation explained by DNA test set to heritability of BREEDPLAN records To obtain a DNA with this accuracy would require ~ 2,500 Wagyu records DNA tests developed in one breed do not predict accurately when applied to other breeds

29 Results: Increase in index accuracy from DNA testing Variable Unit Information available FEEDLOT INDEX Terminal Maternal Accuracy of the index r Performance Records Records + DNA test (+23%).27 (+30%)

30 Results: Combined value per DNA test (assuming a perfect market) Variable Increased value derived from G in commercial sires Increased value derived from G in stud sires Total value per test to seedstock operator Unit AU$/ DNA test AU$/ DNA test AU$/ DNA test Information available Records + DNA test Records + DNA test Records + DNA test FEEDLOT INDEX Terminal Maternal $30 $67 $109 $191 $139 $258

31 Beef industry sector where value of ΔG in improved commercial bull is derived

32 These are the average BMS of progeny from each of two sires BMS What is the difference in profitability between the two bulls that sired these carcases?

33 It depends If no other differences in days on feed or EMA or carcase weight of offspring then clearly the bull with the progeny with an average BMS of 6.86 would be superior AUSMEAT Marble Score Carcase $/kg 9 & 9+ $ $ $ $ $ $ $ $ kg x 4.60 = $ kg x 6.75 = $2903

34 What if the BMS 6.86 progeny were on feed for an extra 100 days to get to the same carcase weight, but the lower EMA resulted in an inferior dressing and saleable meat % An extra 100 days on feed would cost ~ $340 in feed costs, so would still come out ahead unless SMP% was dramatically reduced. Need to consider all traits when considering breeding objectives although in the case of Wagyu marbling score is by far the major profit driver

35 Summary Selection is meaningless if there is no EBV information Accuracy of EBVs can be improved by Having uniform records on individual and its relatives Maintaining contemporary groups especially in feedlot Having pedigree links between farms Correlations between selection criteria and breeding objectives Training populations of Wagyu cattle with records and genotypes will be needed to develop accurate DNA tests for multigenic traits like marbling score DNA information has the potential to increase the accuracy of marbling score breeding values a trait of great financial importance to Wagyu breeders - and generate value from increased rate of genetic change

36 Acknowledgements CoAuthors: Mike Goddard Julius van der Werf The authors thank Steve Barwick from the Animal Genetics and Breeding Unit of the University of New England for providing selection index economic parameters, Ben Hayes and Jennie Pryce from the Victorian Department of Primary Industries, Australia for helpful discussions. Australian Wagyu Association The DNA value determination project was supported by National Research Initiative competitive grant no ( Integrating DNA information into beef cattle production systems ) from the USDA National Institute of Food and Agriculture Animal Genome Program to AVE.

37 Level of Phenotypic recording 50K genotype results included No recording Weaning weight only All weights including birth Weights plus calving ease Weights, birth and carcase scan traits Weights, birth, scan and fertility Index Domestic Self Replacing Japanese B3 Self Replacing No 0 $2.64 (15%) Yes $3.63 $4.26 (20%) (23%) No 0 $0.58 (2%) Yes $4.34 $4.36 (15%) (15%) $4.35 (24%) $5.38 (30%) $2.00 (8%) $4.72 (16%) $6.24 (33%) $6.89 (37%) $6.45 (20%) $7.58 (24%) $6.73 (36%) $7.24 (39%) $7.65 (25%) $8.38 (28%) $7.08 (39%) $7.56 (41%) $8.55 (30%) $9.21 (32%) Genetic progress in $Indexes with and without the inclusion of the results of the Pfizer 50K Angus test. The accuracy of the Index is shown in brackets. Data from Alex McDonald to be presented at SMO genomics conference

38 Marker location relative to the gene of interest in two breeds when using the (A) 50K SNP chip assay (markers spaced at ~ 70 kb intervals), or (B) the high density 700 K SNP chip assay (markers spaced at ~ 5 kb intervals) Van Eenennaam UNL 1/28/2011 Animal Genomics and Biotechnology Education

39 High density panels offer the opportunity to accelerate discovery of the causal mutations underlying genetic variation especially if combined with full sequence data on key ancestors Van Eenennaam UNL 1/28/2011 Animal Genomics and Biotechnology Education

40 The beef industry needs to share data and profit between sectors to most benefit from genomic selection McEwan, J. C Current status and future of genomic selection. Proceedings of the New Zealand Society of Animal Production 67: Van Eenennaam UNL 1/28/2011

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