Genomic Selection in. Applied Training Workshop, Sterling. Hans Daetwyler, The Roslin Institute and R(D)SVS

Transcription

1 Genomic Selection in Dairy Cattle AQUAGENOME Applied Training Workshop, Sterling Hans Daetwyler, The Roslin Institute and R(D)SVS

2 Dairy introduction Overview Traditional breeding Genomic selection Advantages Disadvantages Genomic selection around the world Summary

3 Dairy Cattle Most are specialised dairy breeds Holstein, Jersey, Brown Swiss, Ayrshire, etc Some dual purpose Simmental, Montbeliarde, Normande, etc

4 Dairy Industry Relies very heavily (>80%) on artificial insemination (AI) Nucleus herds exist but a large part of breeding is still done by farmer breeders Global exchange of genetic material between countries and AI companies International genetic evaluation

5 Production Traits selected for Milk, fat and protein yield... Conformation Udder, legs, capacity... Functional & Health Somatic cell score, fertility,...

6 Cornerstone of genetic progress AI Companies increase the accuracy of selection through progeny testing. Young bulls sire approx. 100 daughters which provide information for their EBV once the daughters produce records Only 1 in 10 (or less) of bulls return to active service Very costly

7 Bull Life cycles Birth 1 yr 2 yr 5 yr 10 yr Selected on parent avg Daughters born Cow Bull is progeny tested Son is progeny tested Birth 1 yr 2 yr 4 yr 7 yr Gives Birth Daughter Gives Birth Son is progeny tested

8 Traditional Breeding Pedigree + Records Estimation Breeding Vl Value Accuracy increased with: Own phenotypic records Information on relatives (sibs, progeny, )

9 Traditional Breeding Works well in: Med.- high heritability traits Own records or progeny data is available Less effective Low heritability traits, sex limited traits Young animals (no records, no progeny)

10 Genotypic Information Thousands of single nucleotide polymorphisms (SNP) are now available in many species SNP have 2 alleles or gene variants

11 Genotypic Information Thousands of single nucleotide polymorphisms (SNP) are now available in many species Recode

12 Genotype Data for Elevation - Chromosome From Filippo Miglior, Canadian Dairy Network.

13 The Opportunity Genotyping gives us picture/snapshot of the genetic makeup of an animal The more SNP the clearer the picture (up to a limit) This new source of information can now (or soon) be used in genetic evaluation by: Combining genotyping data with traditional pedigree and phenotypic records

14 Method Meuwissen et al., Genetics, 2001 Divide the genome into many segments (each with 1+ markers) Estimate the genetic effect of each segment from a sample of individuals Many small black boxes Genotype another population sample and sum the segment effects to get a breeding value for each

15 How is this different? Pedigree + Records + Genomic Data Estimate SNP effects Genomic Breeding Value

16 How is this different? Pedigree + Records + Genomic Data Estimate SNP effects Genomic Breeding Value Genomic Breeding Values for animals WITHOUT records!

17 2 Main Genomic Estimation Methods Genomic BLUP Easy to implement because similar to classic BLUP Bayesian methods More complicated May have higher accuracy than GBLUP Papers say yes, practice says not so much

18 Advantages of Genomic Selection Increase genetic gain By increasing i accuracy of selection Parent avg 40%, Genomic BVs higher By reducing the generation interval Select animals before they are of productive and/or reproductive age Reduce/eliminate the need for progeny testing Reduces cost

19 Bull Life cycles Birth 1 yr 2 yr 5 yr 10 yr Selected on parent avg Daughters born Cow Bull is progeny tested Son is progeny tested Birth 1 yr 2 yr 4 yr 7 yr Gives Birth Daughter Gives Birth Son is progeny tested

20 Life cycles Bull Select Select Select Great- Sons here Grand-sons grand-sons Birth 1 yr 2 yr 5 yr 10 yr Selected on parent avg Daughters born Cow Bull is progeny tested Son is progeny tested Birth 1 yr 2 yr 4 yr 7 yr Gives Birth Daughter Gives Birth Son is progeny tested

21 Advantages Lower rate of inbreeding per generation (Daetwyler et al., JABG, 2007) Moves from family selection to individual selection Example: Parent average same for full sib newborns Genomic BV different for full sibs If generation intervals are shortened substantially then annual inbreeding rates could be higher

22 Inbreeding rates of methods 3 Phenotypic Sel. nbreeding rate per gen. (%) 2 1 Classic BLUP Genomic Sel. I Heritability Daetwyler et al., J. Anim. Breed. Genet., 2007

23 Advantages Once marker effects are estimated they can be used for a few generations BUT accuracy will reduce in each generation if not re-estimated t Selection on novel traits, expensive phenotyping New breeding strategies

24 Disadvantages New method, not fully proven and tested Need to genotype a sufficiently large set of animals for accurate marker estimates (Daetwyler et al., PLoS One, 2008) Lower heritability more records needed Marker estimates must be estimated in population that they will be used in Across breed accuracy low

25 Disadvantages Genotypes still costly (125 dairy) Some species have no dense marker maps yet When generation intervals are already low genetic gain due to genomic selection will be less In large litters accuracy can be gained from info on sibs less advantage of GS

26 Genotyping Illumina BovineSNP50 TM BeadChip 58,000 genetic markers, equally spaced 38,416 used in genomic predictions Total of one-third non-informative (currently) or without variation across dairy cattle Openly commercialized to several laboratories in various countries Current genotyping cost $250 USD per animal Miglior, Can. Dairy Network

27 Genomic selection around the world USA & Canada (N.A.) Collaboration New Zealand (LIC) Netherlands (CRV) Australia (ADHIS & co.) Denmark & Sweden (Viking Genetics) Several other countries likely to follow fairly soon Miglior, Can. Dairy Network

28 Australian results Trait Table 1. Accuracy of genomic breeding values calculated at time of birth for Genetic Australia s 2003 progeny test team with two genomic selection methods, BLUP and a Bayesian method (BAYES). Records in reference population Number of SNPs used Sire pathway EBV GBLUP GBayesA AUS Selection Index AUS Profit Ranking Protein yield Protein % Fertility Hayes et al, Review, JDS, 2008

29 North America World wide results GS Accuracy avg 71%, PA 52% Difference between BLUP and Bayesian was 1% Netherlands Large increases in accuracy of GS over PA Use Bayesian methods New Zealand GS accuracy avg 70 80%, PA 58% Hayes et al, Review, JDS, 2008

30 Higher risk vs. Lower risk How will different AI companies use it? Examples: LIC: Reduce progeny testing from 300 to bulls, emphasis on DNA teams Recent recall announcement for HO team(s) CRV: Reduce progeny testing from 500 to 300 bulls, reduce YS incentives North-American units likely to use a more conservative transitional approach Miglior, Can. Dairy Network

31 Possible strategy Genotype a large number of elite females and bull calves Put the best GEBV bulls into organized progeny testing Use the best of those as sires of sons, and in teams for the GEBV bull market Use the best proven bulls for the proven bull market Miglior, Can. Dairy Network

32 How can we do better? Genotype more SNP to get clearer picture of genetic variation (up to a limit) Genotype and get records for more animals Refine estimation methods Determine when to use BLUP or Bayes Develop new estimation methods

33 Summary Dairy industry uniquely suited for genomic selection Faster genetic progress possible with higher accuracy and shorter generation intervals Several countries are implementing genomic selection Hybrid systems merging classic and genomic selection

34 Summary Usefulness of genomic selection depends d on: Population structure/history t t Size of sib families Generation interval Availability of dense marker maps Availability of many genotyped individuals with records

35 Acknowledgements Filippo Miglior, Canadian Dairy Network, Guelph Ben Hayes, Victoria i Dep. Primary Industries, Melbourne And my funding... SABRETRAIN is funded by the Marie Curie Host fellowships for Early Stage Research Training funding mechanism, as part of the 6th Framework Programme of the European Union European Commission.