Marker-Assisted Selection
Alison Van Eenennaam, Ph.D.
Cooperative Extension Specialist
Animal Biotechnology and Genomics
alvaneenennaam@ucdavis.edu
http://animalscience.ucdavis.edu/animalbiotech/
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Overview
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Genetic Markers
What is Marker-Assisted
Selection (MAS) ?
Current Traits with
Markers
Use of Marker-Assisted
Selection
The Future
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
What is DNA ?
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
What is a Genetic Marker ?
A DNA sequence
variation that has
been associated
with a given trait
in one or more
populations
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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)
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Genotyping
Heterozygous
bull
CACGT
CATGT
½
CACGT
Van Eenennaam BIF – 4/2006
½
CATGT
Animal Biotechnology and Genomics Education
Simple (qualitative) traits
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Genotype = phenotype
– Gender (XY = male
XX = female)
– Some genetic diseases
– Double muscling
– Coat color
– Horns
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All or nothing
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
2
Complex (quantitative) traits
Genotype
Environment
Phenotype
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
77 inches ‘tip to tip’
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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.
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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)
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Current applications:
Marker-assisted selection
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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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Potential benefits from MAS are
greatest for traits that
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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
Van Eenennaam BIF – 4/2006
Yep, looks
like none of
‘em were
resistant
Animal Biotechnology and Genomics Education
Traits that are most likely to
benefit from MAS (descending order)
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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.
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Selection 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.
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Selection for Tenderness
$
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Marker-Assisted Selection
(MAS)
Size of the marker effect
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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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Which would you rather have???
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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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Both are important!!
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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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Marker-Assisted Selection
(MAS)
Allele frequencies
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Frequency of the marker*
Reference
Population
Charolais
x
Angus
Hereford
TG5
0
1
2
0
Genotype No. 252 137 20 263
Genotype % 62% 34% 5% 63%
Allele % 78%
22% 79%
409
Total No.
Genotype No. 263 59
2
303
Genotype % 81% 18% 1% 97%
Allele % 90%
10% 99%
324
Total No.
http://www.nbcec.org/
Van Eenennaam BIF – 4/2006
M2
1
139
33%
420
8
3%
2
18
4%
21%
0
0%
1%
311
* These are the frequencies in the
data analyzed and are not necessarily
reflective of any purebred population.
Animal Biotechnology and Genomics Education
Should I use MarkerAssisted Selection ?
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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 ?”
1.
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Should I use DNA-based marker-assisted
selection in my breeding program?
2.
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”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Should I use DNA-based marker-assisted
selection in my breeding program?
3.
Make sure you know what your
results mean

Translation
“every individual receives one allele of
each marker from each parent – so
two is maximum .”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Should I use DNA-based marker-assisted
selection in my breeding program?
4.
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”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Should I use DNA-based marker-assisted
selection in my breeding program?
5.
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”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Should I use DNA-based marker-assisted
selection in my breeding program?
6.
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. ”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Use ALL available information to
select animals that stand out in the
crowd
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Things to think about when using
marker assisted selection
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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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
This is a young industry....
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
“1954 version of what 'home computers'
might look like in 50 years time (i.e. 2004)”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
“what escaped their vision was that science
might come up with new and different ways of
commercializing and using new technologies.”
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Bovine genome
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Van Eenennaam BIF – 4/2006
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
Animal Biotechnology and Genomics Education
21
Chromosome
1
2
4
5
6
7
Birth weight
Weaning wt.
Hot carcass weight
Polled
Marbling
Retail product yield
Rib eye area
Yield grade
Weaning weight
Tenderness
Rib bone
Dressing percent
Rib fat
Birth weight
Ovulation Rate
Tenderness
Weaning weight
Birth weight
Ovulation Rate
Trypanotolerance
Van Eenennaam BIF – 4/2006
8
9
12
14
15
16
18
19
22
23
29
Backfat
Birth weight
Weaning wt
Behavior
Weaning wt
Birth weight
ADG
Backfat
Birth weight
Carcass wt
Weaning weight
Yearling weight
Tenderness
Birth weight
Birth weight
Ovulation Rate
Carcass wt
Live weight
Weaning wt
Carcass wt
Tenderness
Animal Biotechnology and Genomics Education
Future Marker-assisted selection
will focus on “sustainable traits”
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Product quality
Genetic disease
resistance
– e.g. mastitis resistance
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Residual feed
efficiency
Health
Robustness
Adaptability
Stayability
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
An animal is born and tagged...
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
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.
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
...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
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Marker-Driven Selection (MAD)
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education
Marker-Assisted Selection
Van Eenennaam BIF – 4/2006
(MAS)
Animal Biotechnology and Genomics Education
Questions ?
Van Eenennaam BIF – 4/2006
Animal Biotechnology and Genomics Education