Marker-Assisted Selection

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Marker-Assisted Selection

• Alison Van Eenennaam, Ph.D.
• Cooperative Extension Specialist
• Animal Biotechnology and Genomics
• alvaneenennaam_at_ucdavis.edu
• http//animalscience.ucdavis.edu/animalbiotech/

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Overview

• Genetic Markers
• What is Marker-Assisted Selection (MAS) ?
• Current Traits with Markers
• Use of Marker-Assisted Selection
• The Future

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What is DNA ?
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What is a Genetic Marker ?
A DNA sequence variation that has been associated
with a given trait in one or more populations
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What is a SNP ? SNPs Single nucleotide
polymorphisms
SNPs are the most common and stable type of DNA
marker in cattle and are ideally suited for
automated, economical genetic testing
(genotyping)
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Genotyping
Heterozygous bull
CACGT CATGT
½
½
CACGT
CATGT
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Simple (qualitative) traits

• Genotype phenotype
• Gender (XY male
• XX female)
• Some genetic diseases
• Double muscling
• Coat color
• Horns
• All or nothing

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Complex (quantitative) traits
Genotype
Environment
Phenotype
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Traditional Genetic Evaluation and EPD-based
Selection
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
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77 inches tip to tip
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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.
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Marker-Assisted Selection (MAS)

• Assisted - To give help or support to, especially
  as a subordinate or supplement aid
• Driven - Powered, operated, or controlled to
  exert inescapable or coercive pressure on

Marker-Driven Selection (MAD)
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Current applications Marker-assisted selection

• Testing for genetic defects e.g. BLAD
• Testing for single gene traits e.g. coat color
• Marker-assisted selection for multigenic or
  quantitative traits e.g.
  tenderness

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Potential benefits from MAS are greatest for
traits that

• Are difficult or expensive to measure,
• Cannot be measured until late in life or after
  the animal is dead,
• Are not currently selected for because they are
  not routinely measured,
• Have low heritability,
• Have undesired correlations with undesirable
  traits

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

• Simply inherited genetic defects,
• carcass quality and palatability attributes,
• fertility and reproductive efficiency,
• maintenance requirements
• carcass quantity and yield,
• milk production and maternal ability, and
• growth performance.

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Selection for Marbling

• Progeny from Angus bulls with high (gt.4) and low
  (lt -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. 741009-1013.
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Selection for Tenderness

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Marker-Assisted Selection (MAS)Size of the
marker effect

• Size of the effect of the marker
• What proportion of the variation in the trait of
  interest is attributable to the favorable of the
  DNA-marker allele ?
• How can a well-proven bull with a high EPD for a
  given trait be carrying the wrong (unfavorable)
  marker genotype for the trait ?
• Genetic progress will be hindered if the presence
  of two copies of a single marker is used as a
  litmus test for bull selection

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Which would you rather have???

• A bull that is homozygous for a positive
  genetic variant with a trait EPD of 3, or
• A bull carrying no copies of that genetic variant
  with a trait EPD of 3

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Both are important!!

• The homozygous bull is a source of favorable
  form of the genetic variant. Can eventually be
  used to create homozygous calves
• The other bull contributes other favorable genes,
  which will improve the other genes affecting the
  trait.
• Breeding the marker-associated form of the gene
  into the bull that has no copies should improve
  the trait by combining all of the good forms of
  the genes together in one animal

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Marker-Assisted Selection (MAS)Allele frequencies

• Frequency of the marker

These are the frequencies in the data analyzed
and are not necessarily reflective of any
purebred population.
http//www.nbcec.org/
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Should I use Marker-Assisted Selection ?
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Should I use DNA-based marker-assisted selection
in my breeding program?

• The increased economic returns from increasing
  the allele frequency of the marker or genetic
  gain in the trait of interest as a result of
  using the markers must outweigh the cost of
  genotyping
• Translation
• will marker assisted selection make you money
  ?

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

• How much of the additive genetic variation in the
  trait of interest does this marker explain in
  your herd?
• Translation
• the weight a marker is given should be
  proportional to its effect on the trait

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

• Make sure you know what your results mean
• Translation
• every individual receives one allele of each
  marker from each parent so two is maximum .

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

• What form of the marker do you want for your
  production environment or your breed ?
• Translation
• Make sure you know what it is that you
  want to select for in your situation

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

• What are you giving up to use animals that are
  carrying the marker of interest ?
• Translation
• Selection should focus on more than a single
  marker associated with a single trait
  

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

• Could good progress in that trait be achieved
  without the expense of marker assisted selection
  ?
• (i.e. just use EPDs)
• Translation
• Although DNA-based markers are relatively
  new and alluring, they are not a silver bullet.
  

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Use ALL available information to select animals
that stand out in the crowd
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Things to think about when using marker assisted
selection

• MAS is likely to accelerate genetic progress in
  some traits better than others
• Too much emphasis on one gene/trait is not
  desirable
• Validation and breed-specific allele frequencies
• Genetic markers will not overcome a poor
  environment
• Markers are not a replacement for EPDs
• Ensure you weigh the cost and benefits of using
  MAS in your production system just as you would
  with any other input

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This is a young industry....
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1954 version of what 'home computers' might look
like in 50 years time (i.e. 2004)
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Wrong Expert Predictions
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
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what escaped their vision was that science might
come up with new and different ways of
commercializing and using new technologies.
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Bovine genome

• 30 pairs of chromosomes.
• Roughly the size of the human genome
• 3 billion base pairs
• Human cattle genomes are 83 identical
• The entire project will cost 50 million
• Accelerate gene and marker discovery

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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
6 Birth weight 7
Ovulation Rate Trypanotolerance
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Future Marker-assisted selection will focus on
sustainable traits

• Product quality
• Genetic disease resistance
• e.g. mastitis resistance
• Residual feed efficiency
• Health
• Robustness
• Adaptability
• Stayability

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An animal is born and tagged...
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a SNP panel run on the DNA....
DNA from uniquely IDed calf will be run through a
SNP panel of DNA-markers

• unique permanent genetic fingerprint,
• genetic tests for markers linked to
  economically relevant traits, and to
• assertain parentage.
• Genotype data then stored for future traceback of
  products derived from that animal, and marker
  data incorporated into herd and breed EPD
  calculations.

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

• Results are used to make decisions
  regarding
• Health product needs
• Feeding strategies
• Markets
• Breeding decisions

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Marker-Driven Selection (MAD)
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Marker-Assisted Selection (MAS)
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Questions ?