blup and genomic selection• would like records before selection • need to know genetic...

Van Eenennaam WAGYU 2011 Van Eenennaam WAGYU 2011 Animal Genomics and Biotechnology Education

Alison Van Eenennaam

Cooperative Extension Specialist Animal Biotechnology and Genomics University of California, Davis, USA [email protected] http://animalscience.ucdavis.edu/animalbiotech/

BLUP and Genomic Selection

mailto:[email protected]

http://animalscience.ucdavis.edu/animalbiotech/



Van Eenennaam WAGYU 2011 Van Eenennaam WAGYU 2011

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

Animal Biotechnology and Genomics Education


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



However breeding based on objective performance recording has been spectacularly successful…..


Image from: Dekkers, J.C.M, and F. Hospital, 2002. The use of molecular genetics in the

improvement of agricultural populations. Nature Reviews Genetics 3: 22-32

Average milk production per lactation of US Holstein cows has nearly doubled during the past 40 years


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


Van Eenennaam WAGYU 2011

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



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



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



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



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)



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.



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).



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


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

The genome age

SNP (Single Nucleotide Polymorphism)

A DNA sequence variation that varies sufficiently between individuals that its inheritance can be tracked through families


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)

Van Eenennaam WAGYU 2011 Van Eenennaam WAGYU 2011 Animal Biotechnology and Genomics Education

market

To date DNA

tests have not

accounted for

sufficient

genetic

variation to

make them

cost-effective


BREAKDOWN OF FACTORS THAT INFLUENCE FINAL PHENOTYPE

60% ENVIRONMENT

40% GENETICS (h2)

DNA TEST

OTHER GENES 85%

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

Trait h2

Pfizer 50K HD in Angus Number of animals in

training population1

% Genetic variation (r2)

Company estimate (2010)1

Australian Calibration

(2010)2

Average Daily Gain 0.28 1254 30% 1-10% Net Feed Intake 0.39 1254 12% 0 Dry matter intake 0.39 1254 11% 4-5% Tenderness 0.37 1445 26% n.d. Calving Ease (Direct) 0.1 1188 22% 6% Birth weight 0.31 1169 28% 12-16% Weaning Weight 0.25 1192 32% 12-19% Calving ease (maternal) 0.1 1177 40% 4% Milking Ability 0.25 1187 27% 10-14% Carcass weight 0.39 1100 29% 6-13% Backfat thickness 0.36 1097 40% 14-19% Ribeye area 0.4 1114 29% 10-20% Marbling score 0.37 1143 34% 4-11%

1 Pfizer Animal Genetics. 2010. Technical Summary.

http://www.pfizeranimalgenetics.com/sites/PAG/Documents/50K%20Tech%20Summary.pdf 2 Animal Genetics and Breeding Unit (AGBU). 2010. Evaluation of Pfizer Animal Genetics HD 50K MVP Calibration.

http://agbu.une.edu.au/pdf/Pfizer_50K_September%202010.pdf


Dairy industry is ideally suited to genomic selection

Training population THOUSANDS of genotyped bulls with high accuracy records

Validation: New Progeny Tested Bulls

Application: New Sire Candidates

r0

r1

Slide courtesy of Marc Thallman, US MARC

Degree of genetic relationship

between populations

(ideally similar)

Predicted to

double the rate

of genetic gain

in the dairy

cattle industry



Young sire Parent Average

x

AS AD

Mendelian Sampling ?

Accuracy 0.20

Example: How will genomic selection help estimating the breeding value of dairy sires

5 years; >>>> cost

x

AS AD

Mendelian Sampling

Young sire Progeny Test

Accuracy 0.80

x

AS AD

Mendelian Sampling

Accuracy 0.65

Young sire Genomic Selection

?

Birth Birth; <<<< cost

Animal Biotechnology and Genomics Education Slide courtesy of Gonzalo Rincon, UC Davis


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



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. 2010. Value of DNA information for beef

bull selection. 9th World Congress of Genetics Applied to Livestock Production. Leipzig, Germany


To value genetic gain need a $Index


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



Variable Unit Information

available

FEEDLOT INDEX

Terminal Maternal

Accuracy of the index

r

Performance Records

.26 .19

Records + DNA test

.32

(+23%)

.27

(+30%)


Results: Increase in index

accuracy from DNA testing


Variable Unit Information

available FEEDLOT INDEX

Terminal Maternal

Increased

value derived

from ∆G in

commercial

sires

AU$/

DNA

test

Records +

DNA test $30 $67

Increased

value derived

from ∆G in

stud sires

AU$/

DNA

test

Records +

DNA test $109 $191

Total value

per test to

seedstock

operator

AU$/

DNA

test

Records +

DNA test $139 $258


Results: Combined value per DNA

test (assuming a perfect market)


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



These are the average BMS of progeny from each of two sires


3.20 6.86 BMS

What is the difference in profitability between

the two bulls that sired these carcases?


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+ $11.00

8 $9.20

7 $7.70

6 $6.75

5 $5.60

4 $4.80

3 $4.60

2 $4.00

430 kg x 4.60 = $1978

430 kg x 6.75 = $2903


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


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



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. 2009-55205-05057 (“Integrating DNA information into beef cattle production systems”) from the USDA National Institute of Food and Agriculture Animal Genome Program to AVE.

Acknowledgements


Van Eenennaam WAGYU 2011 Animal Biotechnology and Genomics Education

Level of Phenotypic recording

Index

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

Domestic Self Replacing

No 0 $2.64 (15%)

$4.35 (24%)

$6.24 (33%)

$6.73 (36%)

$7.08 (39%)

Yes $3.63 (20%)

$4.26 (23%)

$5.38 (30%)

$6.89 (37%)

$7.24 (39%)

$7.56 (41%)

Japanese B3 Self Replacing

No 0 $0.58 (2%)

$2.00 (8%)

$6.45 (20%)

$7.65 (25%)

$8.55 (30%)

Yes $4.34 (15%)

$4.36 (15%)

$4.72 (16%)

$7.58 (24%)

$8.38 (28%)

$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

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

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


The beef industry needs to share data and profit between sectors to most

benefit from genomic selection

McEwan, J. C. 2007 Current status and future of genomic selection. Proceedings of

the New Zealand Society of Animal Production 67: 147-152.

Van Eenennaam UNL 1/28/2011