# Presentation: 820745

## Reliability of Genomic Predictions for North American Dairy Bulls 

## Sequencing and Genotyping

**Cattle genome sequenced in 2004**
**30**** chromosome pairs (including X,Y)**
**3 billion**** letters from each parent**
**Illumina BovineSNP50 BeadChip**
**58,000**** genetic markers in 2007**
**38,416**** used in genomic predictions**
**Current cost ****<**** ****$250**** per animal**

## Experimental Design

**Compute genomic evaluations and parent averages from 2003 data**
**3576**** older Holstein bulls born ****1952-1998**
**Compare ability to predict daughter deviations in 2008 data**
**1759**** younger bulls born ****1999-2002**
**Test results for ****27 traits****: 5 yield, 5 health, 16 conformation, and Net Merit**

## Genotyped Animals (n=6005)As of April 2008

## Genomic Methods

**Direct**** genomic evaluation**
**Inversion for linear prediction, REL**
**Iteration for nonlinear prediction**
**Combined**** genomic evaluation**
**3 x 3 selection index combining direct genomic PTA, traditional PA or PTA, and subset PA or PTA by REL**

## Marker Effects for Net Merit

## Significance Tests for Net Merit

## Major Gene on Chromosome 18Net Merit, Productive Life, Calving Ease, Stature, Strength, Rump Width

## Marker Effects for Milk

## Marker Effects for Final Score

## Linear and Nonlinear Predictions

**Linear model**
**Infinitesimal alleles model in which all loci have non-zero effects**
**Nonlinear models**
**Model A:**** infinitesimal alleles with a heavy-tailed prior**
**Model B:**** finite locus model with  normally-distributed marker effects**
**Model AB:**** finite locus model with a heavy-tailed prior**

## Nonlinear and Linear Regressions for marker allele effects 

## R2 for linear and nonlinear predictions

## R2 vs. Reliability

**Adjust the observed genomic R****2**
**Daughter deviations contain error**
**Divide by REL of 2008 deviations**
**Parents are selected**
**Add difference of PA R****2**** from expected **
**Adjust theoretical genomic REL**
**Genotypes contain a few errors **
**QTLs are located between SNPs**

## R2 and Reliabilities for Traditional and Genomic Predictions

|  | Squared corr (x100) |  | Reliability |  |  |
| --- | --- | --- | --- | --- | --- |
|  |  |  | Traditional | Genomic | Genomic |
| Trait | PA | Genomic | PA | Realized | Gain |
| Net Merit | 11 | 28 | 30 | 53 | 23 |
| Milk | 28 | 49 | 35 | 58 | 23 |
| Fat | 15 | 44 | 35 | 68 | 33 |
| Protein | 27 | 47 | 35 | 57 | 22 |
| Fat %  | 25 | 63 | 35 | 78 | 43 |
| Protein % | 28 | 58 | 35 | 69 | 34 |

## R2 and Reliabilities for Traditional and Genomic Predictions

|  | Squared corr (x100) |  | Reliability |  |  |
| --- | --- | --- | --- | --- | --- |
|  |  |  | Traditional | Genomic | Genomic |
| Trait | PA | Genomic | PA | Realized | Gain |
| Longevity | 17 | 27 | 27 | 45 | 18 |
| SCS | 23 | 38 | 30 | 51 | 21 |
| Fertility | 20 | 29 | 25 | 41 | 16 |
| S.calf ease | 27 | 29 | 28 | 31 | 3 |
| D.calf ease | 14 | 22 | 25 | 40 | 15 |
| Final score | 23 | 36 | 24 | 42 | 18 |

## Reliability Gains for Proven Bulls

**Bulls included in test had:**
**>10 daughters in August 2003**
**>10% increase in reliability by 2008**
**Numbers of bulls in test ranged from 104 to 735 across traits**
**Predicted the change in evaluation**
**Significant increase in R****2**** (P < .001) for ****26**** of ****27**** traits**

## Net Merit by Chromosome for O ManTop bull for Net Merit

## SNPs on X Chromosome

**Each animal has two evaluations:**
**Expected genetic merit of daughters**
**Expected genetic merit of sons**
**Difference is sum of effects on X**
**SD = .1 ****σ****G****, smaller than expected**
**Correlation with sire’s daughter vs. son PTA difference was significant (P<.0001), regression close to 1.0 **

## X, Y, Pseudo-autosomal SNPs

**487 SNPs**

**35 SNPs**

**0 SNPs**

**35 SNPs**

## Clones and Identical Twins21HO2121, 21HO2125, 21HO2100, CAN6139300, CAN6139303

|  | Traditional |  |  | Genomic |  |
| --- | --- | --- | --- | --- | --- |
| Bull | Dtrs | NM$ | REL | NM$ | REL |
| Triton - ETN | 98 | -363 | 82 | -371 | 91 |
| Triad - ETN | 26 | -306 | 68 | -370 | 91 |
| Trey - ETN | 108 | -395 | 83 | -371 | 91 |
| Loyalty | 108 | -185 | 78 | -196 | 87 |
| Lauriet | 83 | -203 | 76 | -196 | 87 |

## Value of Genotyping More SNP9,604 (10K), 19,208 (20K), and 38,416 (40K) SNP

|  | REL of PA | Genomic REL |  |  |
| --- | --- | --- | --- | --- |
| Trait |  | 10K | 20K | 40K |
| Net Merit $ | 30 | 48 | 50 | 53 |
| Milk yield | 35 | 53 | 56 | 58 |
| Fat yield | 35 | 64 | 66 | 68 |
| Protein yield | 35 | 54 | 56 | 57 |
| Productive Life | 27 | 38 | 41 | 45 |
| SCS (mastitis) | 30 | 45 | 47 | 51 |
| Dtr Preg Rate | 25 | 37 | 39 | 41 |

## Value of Genotyping More Bulls

| Bulls |  | R2 for Net Merit |  |  |
| --- | --- | --- | --- | --- |
| Predictor | Predictee | PA | Genomic | Gain |
| 1151 | 251 | 8 | 12 | 4 |
| 2130 | 261 | 8 | 17 | 9 |
| 2609 | 510 | 8 | 21 | 13 |
| 3576 | 1759 | 11 | 28 | 17 |

## Simulated ResultsWorld Holstein Population

**15,197**** older and ****5,987 ****younger bulls in Interbull file**
**40,000 SNPs and 10,000 QTLs **
**Provided timing, memory test**
**Reliability vs parent average REL**
**REL = corr****2**** (EBV, true BV) **
**80% vs 34%**** expected for young bulls**
**72% vs 30%**** observed in simulation**

## Brown Swiss Results

**Nearly all proven bulls genotyped**
**Data from ****225**** bulls born before 1999 **
**Predict ****118**** bulls born during or after 1999**
**Gains in young bull reliability **
**Expected to be ****1%**** to ****3%**
**Actual gains were about ****2%**** for yield**
**Little or no gain for other traits**
**Cooperation with Europe is needed**

## Jersey Genotypes

**Same experimental design**
**DNA available for ****766**** bulls **
**Total of ****594**** genotyped as of June**
**Results not available yet**
**Gains in reliability expected to be proportional to number of bulls genotyped**

## Expected vs Observed ReliabilityHolsteins

**Reliability for predictee bulls **
**Traditional PA: ****27%**** average across traits**
**Genomic: ****63%**** expected vs. ****50%**** observed**
**Observed range ****78%**** (fat pct) to ****31% ****(SCE)**
**PTA regressions ****.8**** to ****.9**** of expected**
**Multiply genomic daughter equivalents by ****.7**** to make expected closer to observed **
**For example, 16 * .7 = ****11**
**Include polygenic effect, less than 5% **

## Genetic ProgressHolsteins

**Assume 60% REL for net merit**
**Sires mostly ****2**** instead of ****6**** years old**
**Dams of sons mostly heifers with 60% REL instead of cows with phenotype and genotype (66% REL)**
**Progress could increase by ****>50%**
**0.37 vs. 0.23 genetic SD per year**
**Reduce generation interval more than accuracy**

## Genetic Evaluation Advancesand increases in genetic progress

| Year | Advance | % Gain |
| --- | --- | --- |
| 1935 | Daughter-dam comparison | 100 |
| 1962 | Herdmate comparison | 50 |
| 1973 | Records in progress | 10 |
| 1974 | Modified cont. comparison | 5 |
| 1977 | Protein evaluated | 4 |
| 1989 | Animal model | 4 |
| 1994 | Net merit, PL, and SCS | 50 |
| 2008 | Genomic selection | >50 |

## How Related are Relatives?Correction

**Example: Full sibs **
**Share ****50% ****±**** 5%**** of their DNA on average (in cattle)**
**SD ****3.5%**** reported previously was low**
**For any diploid species, general formula is ****50% ****± 50% / [2(C + L)]****.5****, where C is number of chromosomes and L is genome length in Morgans**

## Conclusions

**Genomic predictions significantly better than parent average (P < .0001) for all 26 traits tested**
**Gains in reliability equivalent on average to ****11**** daughters with records **
**Analysis used ****3576**** historical bulls **
**April data included ****5285**** proven bulls**
**High REL requires many genotypes**

## Acknowledgments

**Genotyping and DNA extraction:**
**BFGL, U. Missouri, U. Alberta, GeneSeek, GIFV, and Illumina**
**Computing:**** **
**AIPL staff (Mel Tooker, Leigh Walton, etc.)**
**Funding:**** **
**National Research Initiative grants**
**2006-35205-16888, 2006-35205-16701**
**Agriculture Research Service**
**Contributors to Cooperative Dairy DNA Repository (CDDR)**

## CDDR Contributors

**National Association of Animal Breeders (NAAB, Columbia, MO)**
**ABS Global (DeForest, WI)**
**Accelerated Genetics (Baraboo, WI)**
**Alta (Balzac, AB)**
**Genex (Shawano, WI)**
**New Generation Genetics (Fort Atkinson, WI)**
**Select Sires (Plain City, OH)**
**Semex Alliance (Guelph, ON)**
**Taurus-Service (Mehoopany, PA)**