# Presentation: 464545

## North American Cooperation in Genomic Prediction 

## 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**

## History of Genomic Cooperation

**1992**** USDA request for CAN, USA AI companies to join Dairy Bull DNA Repository maintained at U. Illinois**
**CIAQ (Brian Van Doormaal) provided 1110 straws from 110 bulls**
**1999**** Cooperative Dairy DNA Repository maintained at Beltsville, MD**
**Semex and Alta contributed semen for all progeny tested bulls**

## 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)**

## Genotype Data for Elevation             Chromosome 1

- 1000111220020012111011112111101111001121100020122002220111
- 1202101200211122110021112001111001011011010220011002201101
- 1200201101020222121122102010011100011220221222112021120120
- 2010020220200002110001120201122111211102201111000021220200
- 0221012020002211220111012100111211102112110020102100022000
- 2201000201100002202211022112101121110122220012112122200200
- 0200202020122211002222222002212111121002111120011011101120
- 0202220001112011010211121211102022100211201211001111102111
- 2110211122000101101110202200221110102011121111011202102102
- 1211011022122001211011211012022011002220021002110001110021
- 1021101110002220020221212110002220102002222121221121112002
- 0110202001222222112212021211210110012110110200220002001002
- 0001111011001211021212111201010121202210101011111021102112
- 2111111212111210110120011111021111011111220121012121101022
- 202021211222120222002121210121210201100111222121101

**Notes:**
0 = homozygous for first allele ; 1 = heterozygous ; 2 = homozygous for second allele 
This shows 864 alleles. (out of over 2000)  If we were to show all of the base pairs for the first chromosome, I would have to show you 1 slide, per second for over 3 days.
Vast portions of the chromosome are homozygous, and not interesting,,  ie all animals have the same DNA sequence.  Looking at a foundation bull such as elevation shows many alleles are heterozygous.
Pedigree analysis by Holstein Association 956 bulls in the April 2008 sire guide red book had 15.2% genes in common with Elevation.  Seven generations back, showed on average Elevation appearing 3.5 times in these bulls pedigrees.  8 generations 2 times.  Nine generations showed Elevation an average of once per bull.   
So what does this really mean?

## Genotype Data from Inbred BullChromosome 24 of Megastar

- 1021222101021021011102110112112211211002202000222020002020220
- 0000220020222202202000020020222222000020222200000220200002002
- 2002000000222200022220000000000020222022002000222020222220002
- 2022222222200002002202022202000200022000000002202220000002200
- 2020002222002020020020202220222222220222020002022022022220202
- 2202020202200022002220220022200000220200002002002000200222220
- 0022220202002220022202000020200000022222020200002002002222000
- 2022022220022000222202200222202020002202202222002220022000200
- 2202000002200220222000022000022000222202002222000220020020202
- 2020002220002220022202202200000220220020020020220002000222202
- 2002220020220200222202220000020220002020020202000220022000002
- 2022200202220200022002000200022002002000200220222220022022000
- 2000020002000020220020220200200002220000222002000200222000022
- 0220020022002202202020202020200022202000220200202202220220000
- 2020200002020200022222200222200020022022220000020220020200202
- 022022020200002000200220220002200

**Notes:**
Look at the genotype of an Inbred Bull.  This is chromosome 24 from Megastar, a double grandson of Aerostar, who has Elevation as a paternal grandsire, and is also on his maternal side.   Vast portions are homozygous;  due to Elevation.

## Close Inbreeding (F=14.7%): Double Grandson of Aerostar

**Aerostar**

**Aerostar**

**Megastar**

**Chromosome 24**

**Notes:**
More conventional way of looking at this.  So now, moving on to the actual experiment:

## Holstein 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 Holsteins (n=6005)As of April 2008

## Jersey and Brown Swiss

**Jersey experimental design**
**Data from ****579**** bulls born before 1999 and ****204**** cows with data before 2003**
**Predict ****352**** bulls born during or after 1999**
**Brown Swiss experimental design**
**Data from ****225**** bulls born before 1999 **
**Predict ****118**** bulls born during or after 1999**

## Genomic Methods

**Direct**** genomic evaluation**
**Evaluate genotyped animals by summing effects of 38,416 genetic markers (SNPs)**
**Combined**** genomic evaluation**
**Include phenotypes of nongenotyped ancestors by selection index**
**Transferred**** genomic evaluation**
**Propagate info from genotyped animals to nongenotyped relatives (not done yet)**

## Significance Tests for Net Merit

## Marker Effects 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

## Reliability Gain by Breed

| Trait | HO | JE | BS |
| --- | --- | --- | --- |
| Net merit | 23 | 14 | 3 |
| Milk | 23 | 6 | 0 |
| Fat | 33 | 10 | 5 |
| Protein | 22 | 3 | 1 |
| Fat % | 43 | 31 | 10 |
| Protein % | 34 | 22 | 5 |
|  |  |  |  |

## Reliability Gain by Breed

| Trait | HO | JE | BS |
| --- | --- | --- | --- |
| Productive life | 18 | 8 | 2 |
| Somatic cell score | 21 | 3 | 16 |
| Dtr pregnancy rate | 16 | 3 | - |
| Final score | 18 | 4 | - |
| Udder depth | 35 | 11 | 3 |
| Foot angle | 14 | 8 | - |
| Stature | 26 | 8 | 3 |

## Reliability Gains for Proven Bulls

**Proven 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**

## 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 |

## Genetic Evaluation Timing

**CAN, USA had same genetic evaluation schedule since early ****1980’s**
**Same with 2X, 4X, and 3X releases per year**
**Files exchanged 1 week before a combined release, ****1993-1996**
**Interbull evaluations began in ****1995**
**MACE methods developed in CAN**
**Correlation estimation programs from USA **
**First director: PhD in USA, post-doc in CAN**
**MACE conformation by N.A. Consortium**

## CAN, USA Combined Data

**Evaluations tested and reported in ****1991**
**Banos and Wiggans, Robinson and Wiggans, Powell et al, Wiggans et al**
**Both countries used Cornell computer**
**Animal models applied to yield data of Jerseys and Ayrshires**
**Correlations .98 and .96 between combined vs. converted evaluation**

## Conclusions

**Genomic predictions significantly better than parent average (P < .0001) for all 26 traits tested**
**High reliability requires many genotypes and phenotypes**
**Close cooperation between ****CAN**** and ****USA**** will continue**
**Science, software, and data sharing**

## 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)**