Marker-Assisted Selection

Animal Biotechnology and Genomics Animal Biotechnology and Genomics Education Education

Van Eenennaam BIF – 4/2006Van Eenennaam BIF – 4/2006

Marker-Assisted Selection

Alison Van Eenennaam, Ph.D.Alison Van Eenennaam, Ph.D.Cooperative Extension Specialist Cooperative Extension Specialist

Animal Biotechnology and GenomicsAnimal Biotechnology and Genomics

[email protected]@ucdavis.edu

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



OverviewOverview

Genetic Markers Genetic Markers What is Marker-What is Marker-

Assisted Selection Assisted Selection (MAS) ?(MAS) ?

Current Traits with Current Traits with MarkersMarkers

Use of Marker-Use of Marker-Assisted SelectionAssisted Selection

The Future The Future



What is DNA ?



What is a Genetic Marker ? What is a Genetic Marker ?

A DNA sequence

variation that has been

associated with a given trait in

one or more populations



What is a SNP ? What is a SNP ? SNPsSNPs = Single nucleotide = Single nucleotide

polymorphismspolymorphisms

SNPs are the most common and stable type of DNA marker in cattle and are ideally suited for automated, economical genetic testing (genotyping)



GenotypingGenotyping

CACGT

CATGT

CACGT CATGT

½ ½

Heterozygous bull



Simple (qualitative) Simple (qualitative) traitstraits

Genotype = phenotypeGenotype = phenotype– Gender (XY = maleGender (XY = male

XX = female)XX = female)– Some genetic diseasesSome genetic diseases– Double musclingDouble muscling– Coat colorCoat color– HornsHorns

All or nothingAll or nothing



2Complex (quantitative)

traits

Environment

Phenotype

Genotype



Traditional Genetic Traditional Genetic Evaluation and EPD-based Evaluation and EPD-based SelectionSelection

Selection on EPDs derived from the observable performance of the animal and its relatives has the effect on increasing the frequency of favorable alleles (and sometimes unfavorable alleles) without knowing the corresponding genes and molecular mechanisms



77 inches ‘tip to 77 inches ‘tip to tip’tip’



Commercial companies are now offering DNA markers for use in

Marker-Assisted Selection (MAS) for given traits

Marker-assisted selection is the process of using the results of DNA testing to assist in the selection of

individuals to become parents in the next generation.



Marker-Assisted Selection Marker-Assisted Selection (MAS)(MAS)

AssistedAssisted - To give help or support - To give help or support to, especially as a subordinate or to, especially as a subordinate or supplement; aidsupplement; aid

DrivenDriven - Powered, operated, or - Powered, operated, or controlled; to exert inescapable controlled; to exert inescapable or coercive pressure on or coercive pressure on

Marker-Driven Selection (MAD)



Current applications: Current applications: Marker-assisted selection

Testing for genetic defects e.g. BLADTesting for genetic defects e.g. BLAD Testing for single gene traits e.g. Testing for single gene traits e.g.

coat colorcoat color Marker-assisted selection for Marker-assisted selection for

multigenic or quantitative traits multigenic or quantitative traits e.g. tenderness e.g. tenderness



Potential benefits from MAS Potential benefits from MAS are greatest for traits thatare greatest for traits that

Are difficult or expensive Are difficult or expensive to measure,to measure,

Cannot be measured Cannot be measured until late in life or after until late in life or after the animal is dead,the animal is dead,

Are not currently Are not currently selected for because selected for because they are not routinely they are not routinely measured, measured,

Have low heritability, Have low heritability, Have undesired Have undesired

correlations with correlations with undesirable traitsundesirable traits

Yep, looks like none of

‘em were resistant



Traits that are most likely to Traits that are most likely to benefit from benefit from MAS (descending (descending

order)order)

Simply inherited genetic Simply inherited genetic defects, defects,

carcass quality and carcass quality and palatability attributespalatability attributes,,

fertility and reproductive fertility and reproductive efficiency,efficiency,

maintenance requirements maintenance requirements carcass quantity and yield,carcass quantity and yield, milk production and milk production and

maternal ability, andmaternal ability, and growth performance.growth performance.



Selection for MarblingSelection for Marbling

Progeny from Angus bulls with high (>.4) and low (< -0.16) EPDs for marbling were compared. 74% of high offspring graded choice versus 47% of low EPD offspring.

Vieselmeyer, B. A., R. J. Rasby, B. L. Gwartney, C. R. Calkins, R. A. Stock, and J. A. Gosey. 1996. Use of expected progeny differences for marbling in beef: I. Production traits. J Anim Sci. 74:1009-1013.



Selection for TendernessSelection for Tenderness

$




Size of the marker effectSize of the marker effect Size of the effect of the markerSize of the effect of the marker

– What proportion of the variation in the trait What proportion of the variation in the trait of interest is attributable to the favorable of of interest is attributable to the favorable of the DNA-marker allele ? the DNA-marker allele ?

– How can a well-proven bull with a high EPD How can a well-proven bull with a high EPD for a given trait be carrying the “wrong” for a given trait be carrying the “wrong” (unfavorable) marker genotype for the trait ?(unfavorable) marker genotype for the trait ?

– Genetic progress will be hindered if the Genetic progress will be hindered if the presence of two copies of a single marker is presence of two copies of a single marker is used as a litmus test for bull selectionused as a litmus test for bull selection



Which would you rather Which would you rather have???have???

A bull that is A bull that is ‘homozygous’ for a ‘homozygous’ for a positive genetic positive genetic variant with a trait variant with a trait EPD of +3, orEPD of +3, or

A bull carrying no A bull carrying no copies of that copies of that genetic variant genetic variant with a trait EPD of with a trait EPD of +3+3

**



BothBoth are important!! are important!!

The ‘homozygous’ bull is a source of favorable The ‘homozygous’ bull is a source of favorable form of the genetic variant. Can eventually be form of the genetic variant. Can eventually be used to create homozygous calves used to create homozygous calves

The other bull contributes other favorable The other bull contributes other favorable genes, which will improve the other genes genes, which will improve the other genes affecting the trait. affecting the trait.

Breeding the marker-associated form of the Breeding the marker-associated form of the gene into the bull that has no copies should gene into the bull that has no copies should improve the trait by combining all of the good improve the trait by combining all of the good forms of the genes together in one animalforms of the genes together in one animal




Allele frequenciesAllele frequencies Frequency of the marker*Frequency of the marker*

0 1 2 0 1 2Genotype No. 252 137 20 263 139 18Genotype % 62% 34% 5% 63% 33% 4%

Allele % 78% 22% 79% 21%Total No.

Genotype No. 263 59 2 303 8 0Genotype % 81% 18% 1% 97% 3% 0%

Allele % 90% 10% 99% 1%Total No. 311

M2

Hereford

409

324

420

Charolais x

Angus

TG5Reference Population

http://www.nbcec.org/

* These are the frequencies in the data analyzed and are not necessarily reflective of any

purebred population.



Should I use Marker-Should I use Marker-Assisted Selection ?Assisted Selection ?



Should I use DNA-based marker-Should I use DNA-based marker-assisted selection in my breeding assisted selection in my breeding

program?program?

1.1. The increased economic returns The increased economic returns from increasing the allele from increasing the allele frequency of the marker or frequency of the marker or genetic gain in the trait of genetic gain in the trait of interest as a result of using the interest as a result of using the markers must outweigh the cost markers must outweigh the cost of genotypingof genotyping

TranslationTranslation

““will marker assisted selection will marker assisted selection make you money ?”make you money ?”




program?program?

2.2. How much of the additive genetic How much of the additive genetic variation in the trait of interest does variation in the trait of interest does this marker explain in your herd?this marker explain in your herd?

TranslationTranslation““the weight a marker is given should be the weight a marker is given should be

proportional to its effect on the trait”proportional to its effect on the trait”




program?program?

3.3. Make sure you know what your Make sure you know what your results mean results mean

TranslationTranslation““every individual receives one allele every individual receives one allele

of each marker from each parent – of each marker from each parent – so two is maximumso two is maximum .”.”




program?program?

4.4. What form of the marker do you What form of the marker do you want for your production want for your production environment or your breed ?environment or your breed ?

TranslationTranslation “ “Make sure you know what it is Make sure you know what it is

that you want to select for in that you want to select for in your situation”your situation”




program?program?

5.5. What are you giving up to use What are you giving up to use animals that are carrying the animals that are carrying the marker of interest ?marker of interest ?

TranslationTranslation “ “Selection should focus on more than Selection should focus on more than

a single marker associated with a a single marker associated with a single trait” single trait”




program?program?

6.6. Could good progress in that trait be Could good progress in that trait be achieved without the expense of marker achieved without the expense of marker assisted selection ?assisted selection ?

(i.e. just use EPDs)(i.e. just use EPDs)

TranslationTranslation “ “Although DNA-based markers are Although DNA-based markers are

relatively new and alluring, they are not a relatively new and alluring, they are not a silver bullet.silver bullet. ””



Use ALL available information Use ALL available information to select animals that stand out to select animals that stand out

in the crowdin the crowd



Things to think about when Things to think about when using marker assisted using marker assisted

selectionselection

MAS is likely to accelerate genetic progress MAS is likely to accelerate genetic progress in some traits better than othersin some traits better than others

Too much emphasis on one gene/trait is not Too much emphasis on one gene/trait is not desirabledesirable

Validation and breed-specific allele Validation and breed-specific allele frequenciesfrequencies

Genetic markers will not overcome a poor Genetic markers will not overcome a poor environmentenvironment

Markers are not a replacement for EPDs Markers are not a replacement for EPDs Ensure you weigh the cost and benefits Ensure you weigh the cost and benefits

of using MAS in your production system of using MAS in your production system just as you would with any other inputjust as you would with any other input



This is a young This is a young industry....industry....



“1954 version of what 'home computers' might look like in 50 years

time (i.e. 2004)”



“There is no reason anyone would want a computer in their home.”

Ken Olson, president of Digital Equipment Corp. 1977

“I think there's a world market for about five computers”

Thomas J. Watson, chairman of the board of IBM. 1943

Wrong Expert Predictions



“what escaped their vision was that science might come up with new and different ways

of commercializing and using new technologies.”



Bovine genomeBovine genome

30 pairs of 30 pairs of chromosomes.chromosomes.

Roughly the size of the Roughly the size of the human genomehuman genome– 3 billion base pairs3 billion base pairs

Human & cattle genomes are 83% identical

The entire project will The entire project will cost ~ $50 millioncost ~ $50 million

Accelerate gene and Accelerate gene and marker discoverymarker discovery



Chromosome

1 Birth weight Weaning wt. Hot carcass weight Polled

2 Marbling Retail product yield Rib eye area Yield grade Weaning weight

4 Tenderness 5 Rib bone

Dressing percent Rib fat

Birth weight Ovulation Rate Tenderness

Weaning weight

21

6 Birth weight 7 Ovulation Rate

Trypanotolerance

8 Backfat Birth weight Weaning wt

9 Behavior Weaning wt

12 Birth weight 14 ADG

Backfat Birth weight Carcass wt Weaning weight Yearling weight

15 Tenderness 16 Birth weight

18 Birth weight

19 Ovulation Rate 22 Carcass wt 23 Live weight

Weaning wt Carcass wt

29 Tenderness



Future Marker-assisted Future Marker-assisted selection will focus on selection will focus on “sustainable traits”“sustainable traits”

Product qualityProduct quality Genetic disease Genetic disease

resistanceresistance– e.g. mastitis e.g. mastitis

resistance resistance Residual feed Residual feed

efficiencyefficiency HealthHealth RobustnessRobustness AdaptabilityAdaptability StayabilityStayability



An animal is born and An animal is born and tagged...tagged...



a SNP panel run on the a SNP panel run on the DNA....DNA....

DNA from uniquely IDed calf will be DNA from uniquely IDed calf will be run through a SNP panel of DNA-run through a SNP panel of DNA-markersmarkers• unique permanent genetic unique permanent genetic fingerprint,fingerprint,• genetic tests for markers linked to genetic tests for markers linked to economically relevant traits, and economically relevant traits, and toto• assertain parentage. assertain parentage.

Genotype data then stored for Genotype data then stored for future traceback of products future traceback of products derived from that animal, and derived from that animal, and marker data incorporated into herd marker data incorporated into herd and breed EPD calculations.and breed EPD calculations.



...and each animal is then ...and each animal is then managed according to its managed according to its unique genetic potential.unique genetic potential.

Results are used to make Results are used to make decisions regardingdecisions regarding

Health product needs Health product needs Feeding strategiesFeeding strategies MarketsMarkets Breeding decisionsBreeding decisions



Marker-Driven Selection (MAD)






Questions ?Questions ?

Documents

Marker-Assisted Selection