Cracking the code:
The Speed Gene Revealed
Dr. Emmeline Hill
Equinome Ltd., NovaUCD, Belfield Innovation Park, Belfield, Dublin 4
Email: Emmeline.Hill@equinome.com
The horse genome:
the complete complement
of genetic material
ATATTTCCCTAATTATACAGCACTAAAAATAATTTAATACAACAAATACAATTCTTTCTATTTCAAATGTTTGCCTAAATAATATAAAATCTTAATTTCTGAGGAAGTAACATTTCAACTTTTTT
TATGAAGTGTAAATTAAGATTTACTTATTTAAATTATAACTTGAGTTTCACATATAAAGATAAGATTTAAGTGTAGTTTATTTTATTGTTAACACAGACTTTAATTTTTCAAATATCACATTAT
TCTTATTTATAGATTTATTTCTTTTATGAAGTAGTCAAATGAATCAGCTCACCCTTGACTGTAACAAAATACTGTTTGGTGACTTGTGACAGACAGGGTTTTAACCTCTGACAGCGAGATTCA
TGGAGCAGGAGCCAATCATAGATCCTGACGACACTTGTCTCATCAAAGTTGGAATATAAAAAGCCACTTGGAATACAGTATAAAAGATTCACTGGTGTGGCAAGTTGTCTCTCAGACTGTA
GCATTAAAATTTTGCTTGGCATTGCTCAAAAGCAAAAGAAAAGTAAAAGGAAGAAATAAGAGCAAGGAAAAAGATTGAACTGATTTTAAAATCTGCAAAAACTGCAAATCTATGTTTATA
TACCTGTTTGTGCTGATTCTTGCTGGTCCAGTGGATCTAAATGAGAACAGCGAGCAAAAAGAAAATGTGGAAAAAGAGGGGCTGTGCAATGCATGTACTTGGAGACAAAACACTAAATCT
AGAATAGAAGCCATAAAAATTCAAATCTCAGTAAACTGCGCCTGGAAACAGCTCCTAACATCAGCAAAGATGCTATTAGACAACTTTTGCCCAAAGCTCCTCCACTCCGGGAACTGATTGAT
GTACGATGTCCAGAGAGATGACAGCAGTGATGGCTCTTTGGAAGATGATGATTACCACGCGACGACGGAAACAATCATTACCATGCCTACAGAGTGTAAGTAGTCCTGTTAGTGTATATCA
AATTCTGCTGACTGTTGTTCTAGTGTTTATGAGAAACAGATCTATTTTCAGGCTCTTTTAACAAGCTGTTGGCTTGTATGTAAGCAGGAAGGAAAAGAGTTTCTTTTTTTCAAGATTTCATGA
ATTTACTAATGAGACTGAAATCTGCTGCATTATTTGTTTTCTTAGAGAGCTAAAAAGCTAAACAAAATAAAATTCTTGCACAGCATTAATATTATTTAGTTTAATATGACAAATATAACATGC
ATGCTTTCACAGCTTAATACCACCAAGGCAAAAATTGGGAGATAGTACAAGCAATGTTAAAAACTTACATGAGATTTCATAATTGCGTTTGGTTGCCTAAAATAAGCATTTATAATAACAAG
TTTTTCACTAATAATAGAGAAGGAAGAAATTTGTAGACGTTTAGGTCATTTGAGCATTTGCTGAACACCAAAATGACTTCTGTTACTCAAAACTATTTCTCATAGTGTTTTTATGTTCTTCACA
TTAACATATTAGATTTTGAAAGTTATTCCCCTGGAGATTAGGAAAAATATTTTTTAAAATTTAATGTATTAGTAAGAAAAATGATGAAGTAAACATAGCATAATGATAATCATGAGCTAAT
CATAAAATGCCTAATAAATAAACATTTTAATCAAAGAGGTTATAGCTCAGAGTCCTGCTTACACCTTGACCATAGTACTATTGTTGAGAGCACCCGGGGTGCACATTTCCAGGCAGGCACAT
TTAATAATCTCCTAAAATACAATTTTATTCTTCTTGGGAGGGAGGACTACTACCTGTAGTATCTATATTGCTTCTGAAAGATAATATATTTCATATATTCTTTTTGCAGTCAGTTCATAACTAC
CAAGGAAAGGGAGACAGACACCTTCACAGAGAAGGCATGACACGGAAGATTCTGTGCCATGTGTCTGCGATCCTGCTTTACCCAGTGCTTTATCTACTTTAAACAGGACACAACAGTTTCA
TATTGTTCTCCTTATTAAGTAATCAGGTTATAATGCACCAAATAATTTTCCTTTATGACTCTGCTATCAAATAGTCCTGGAGTAGATTTACCTTATTTATAAACAATCTTGGGGAACCAAAATA
AGAAATTGCTAGTGATTTTGCTCACAATGACAGCCTGGCTCTAAAGACAGTATTTTCTAACTTTTGAGATAGCCTGAATATAACATTCAAATTTTTGTGCTAATTACTTGCTTAGCTTTGTTCC
AAAAGGCTATTCCAAAGCCAAAACATAACAGATGTACTATATTTTCTCTTAATTCCCGAGGCTCAGTTAGTTCCTCAGTGTGTCTTGTCCCCAGGTAATTCAGGCCTGGGGGAAGGGTTCCTT
CCAGACTGATTGGTACAGCTGCTCAGTAAGTGTAACTACTCAGATTCCCAAAGAATTCTAAGTGGATGTTCCTCCACGGTGTCTCTTGTTCTCTCTAATCATCATCATTTTAAAATTTCATCCAC
TTCATTCCTTCATAGAATTTTCCTTAGTTCACAGTTTTCTGGAAAAGAAGTAGATTCCTCATAAACAGCTGAAAAAACATATATCAAAAATTCTGAAAGGCTAGAGTAATTATATTCTTTGAT
TTTCTGAGTTATGAATGAAATTCTACATAGTTTTTCACTTTAAAAGACTAAATATATATTCAGTATTCCAATGGAAAAAAAATGTTCACCAACTAATATGGAAGGGTTTACTAATTTTTTATG
AATAATTTCAATAACTCTTTTTCTTTTCTTATTCATTTATAGCTGATCTTCTAATGCAAGTGGAAGGAAAACCCAAATGTTGCTTCTTTAAATTTAGCTCTAAAATACAATACAATAAAGTAGT
GGCCCAACTGTGGATATATCTGAGACCCGTCAAGACTCCTACAACAGTGTTTGTGCAAATCCTGAGACTCATCAAACCCATGAAAGACGGTACAAGGTATACTGGAATCCGATCTCTGAAA
GACATGAACCCAGGCGCTGGTATTTGGCAGAGCATTGATGTGAAGACAGTGTTGCAAAATTGGCTCAAACAGCCTGAATCCAACTTAGGCATTGAAATCAAAGCTTTAGATGAGAATGGT
GATCTTGCTGTAACCTTCCCAAGACCAGGAGAAGATGGGCTGGTAAGTGATAAATGAAAATAATATTCTAACAACCTTGTTATGTTTTTATTCATCATGTGAATGAATAATAGTGGAAAATC
TACCAGTTTCCTATGCTAACAAGCTAGACAAAGGCATCTTACCCCAATGGCAGCCCTGTACCCAATAAAAGTAGGTGTCCAATTTCATATCCAATGAAACACCCTCTTGATATGTCAACTTTG
GAGGATTAAAAAAACGTTATACCATAGTCCTTAACTCCTCAGGGAGTTCTTTGGAATTGGGAATGAAATATAAAGTGCTTTTCATTGATATGCCACATAATTATATGAATAAAAACACAAAA
TTCACAATGGATTCTTGTACATACCCAACAAATTAAACCTTTTCTTCCCCCCAGAAGAGTGTCAAATGTGTTGAAAGTTTTCTGCTTAATAAAGCAGAGTAAAACTTTAAAAATTATAATTAA
ACAATGCTTTTATTTATAGCAATTAAGTACAAAATGTTTAGGCTTATATTTTATTAAATATACCATATTCAAGGTCCCTCATGATAAATATGTTCATTATGTTCATTATTTTGCAGGCTGTTGA
ATTGATGTTTCTGTAGATTATTCATTTATAGCTGATCTTCTAATGCAAGTGGAAGGAAAACCCAAATGTTGCTTCTTTAAATTTAGCTCTAAAATACAATACAATAAAGTAGTAAAGGCCCAA
GTGGATATATCTGAGACCCGTCAAGACTCCTACAACAGTGTTTGTGCAAATCCTGAGACTCATCAAACCCATGAAAGACGGTACAAGGTATACTGGAATCCGATCTCTGAAACTTGACATGA
CCAGGCGCTGGTATTTGGCAGAGCATTGATGTGAAGACAGTGTTGCAAAATTGGCTCAAACAGCCTGAATCCAACTTAGGCATTGAAATCAAAGCTTTAGATGAGAATGGTCATGATCTTG
GTAACCTTCCCAAGACCAGGAGAAGATGGGCTGGTAAGTGATAAATGAAAATAATATTCTAACAACCTTGTTATGTTTTTATTCATCATGTGAATGAATAATAGTGGAAAATCACTACCAG
CCTATGCTAACAAGCTAGACAAAGGCATCTTACCCCAATGGCAGCCCTGTACCCAATAAAAGTAGGTGTCCAATTTCATATCCAATGAAACACCCTCTTGATATGTCAACTTTGCATGAGGAT
AAAAACGTTATACCATAGTCCTTAACTCCTCAGGGAGTTCTTTGGAATTGGGAATGAAATATAAAGTGCTTTTCATTGATATGCCACATAATTATATGAATAAAAACACAAAATCTTCACAA
ATTCTTGTACATACCCAACAAATTAAACCTTTTCTTCCCCCCAGAAGAGTGTCAAATGTGTTGAAAGTTTTCTGCTTAATAAAGCAGAGTAAAACTTTAAAAATTATAATTAAAATACAATGC
TTATTTATAGCAATTAAGTACAAAATGTTTAGGCTTATATTTTATTAAATATACCATATTCAAGGTCCCTCATGATAAATATGTTCATTATGTTCATTATTTTGCAGGCTGTTGATGCATTGATG
TCTGTAGATTATTCATTTATAGCTGATCTTCTAATGCAAGTGGAAGGAAAACCCAAATGTTGCTTCTTTAAATTTAGCTCTAAAATACAATACAATAAAGTAGTAAAGGCCCAACTGTGGATA
TCTGAGACCCGTCAAGACTCCTACAACAGTGTTTGTGCAAATCCTGAGACTCATCAAACCCATGAAAGACGGTACAAGGTATACTGGAATCCGATCTCTGAAACTTGACATGAACCCAGGCG
GGTATTTGGCAGAGCATTGATGTGAAGACAGTGTTGCAAAATTGGCTCAAACAGCCTGAATCCAACTTAGGCATTGAAATCAAAGCTTTAGATGAGAATGGTCATGATCTTGCTGTAACCT
CAAGACCAGGAGAAGATGGGCTGGTAAGTGATAAATGAAAATAATATTCTAACAACCTTGTTATGTTTTTATTCATCATGTGAATGAATAATAGTGGAAAATCACTACCAGTTTCCTATGCT
CAAGCTAGACAAAGGCATCTTACCCCAATGGCAGCCCTGTACCCAATAAAAGTAGGTGTCCAATTTCATATCCAATGAAACACCCTCTTGATATGTCAACTTTGCATGAGGATTAAAAAAAC
The horse genome project
• Completed in January 2007
• Collaborative effort among
scientists
• 1 female Thoroughbred
• The principal goal of the Horse
Genome Project is to benefit the
health and welfare of horses
Science 6 November 2009: Vol. 326. no. 5954, pp. 865 - 867
Twilight
The Horse Genome was
sequenced at The Broad
Institute, MIT & Harvard, Boston
The genetic code
• DNA is the genetic material that spells out the genetic code
• DNA is made up of the letters G A T C
• Approx. 3 billion letters spell out the genetic code
• Genetic material is arranged in 32 pairs of chromosomes
• A chromosome is a long linear DNA molecule with 1000s of genes.
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
Simple trait
Complex trait
• Genes are found across a chromosome like ‘beads on a string’
• There are approx. 25,000 genes in the genome
• Genes contain the ‘recipe’ for proteins
• Proteins are expressed in the cell and are responsible for the physical
expression of the trait
Genotype = The actual genetic make up of an individual
Phenotype = The observed characteristics of an individual
Genotype (genetic
composition)
Actions of other genes and
their products
Environmental influences
Phenotype
Genotype + Environment = Phenotype
How important are genes?
• Definition of a Thoroughbred
relates to its genetic heritage
•
Pedigrees are visual representation
of the ancestral genetic
contributions to an individual
• Provide some indication of the
possible genetic make-up
Genes and performance
• Ability to perform on the racetrack requires the right combination of
genes and a favourable environment
• In humans > 200 genes for health and fitness related traits have been
characterised
• Likely that a large number of genes contribute to performance in an
additive way
What’s the difference?
• Studies have shown 35 – 55 % variation in racetrack performance is
heritable
• When all other things are equal, the genetic make-up of an individual
will almost entirely be responsible for the variation in the phenotype.
• The difference between two individuals is the difference in the spelling
of the genetic code.
Population genomics & selection
Exercise physiology
Functional genomics of exercise
SNP association & racing performance
The Speed Gene - myostatin
• Investigated DNA differences in the myostatin gene in Thoroughbreds
• Myostatin is a gene responsible for muscle mass development
• DNA differences in myostatin are responsible for muscle hypertrophy
phenotypes in cattle, sheep, dogs, mice and humans
The difference in the DNA
• Identified a single DNA difference in the genetic code of myostatin
CT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGATAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGATAAGCCCTGTCATATGATCGTTCCAGAGATATTT
Gene Variant C
Paternal origin (sire)
Pair of
chromosomes
Maternal origin (dam)
Gene Variant T
CT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGATAAGCCCTGTCATATGATCGTTCCAGAGATATTT
Gene Variant C
Paternal origin (sire)
Pair of
chromosomes
Maternal origin (dam)
Gene Variant C
CC
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGATAAGCCCTGTCATATGATCGTTCCAGAGATATTT
Gene Variant T
Paternal origin (sire)
Pair of
chromosomes
Maternal origin (dam)
Gene Variant T
TT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGACAAGCCCTGTCATATGATCGTTCCAGAGATATTT
AGTCTTGACTGATATCTTGTCTATAGTGATTCTAGATAAGCCCTGTCATATGATCGTTCCAGAGATATTT
Paternal origin (sire)
Pair of
chromosomes
Maternal origin (dam)
CC
CT
TT
A test for Class?
• Investigated the frequency of the C:C – types, C:T – types and T:T – types
in 148 unrelated Thoroughbreds
• No difference between Group race winners and non-winners
Best race distance
• Best race distance (BRD)  distance of the highest grade of race won.
• Highly statistically significant (P = 4.85 x 10-8) association with BRD and
genetic type when Group race winners were separated into short and
long distance winners.
• The three genetic types were strongly associated with best race distance:
C:C – short-distance
C:T – middle-distance
T:T – middle/long-distance
179 Group and Listed race winners
n
179
n
179
Gr1
80
5 - 6f
38
Gr2
25
7 - 8f
62
Gr3
46
L
28
9 - 10f 11 - 12f > 13f
35
37
7
Average Best Race Distance
T:T
C:T
C:C
0
2
4
6
furlongs
8
10
12
0.6
0.5
0.4
0.3
0.2
0.1
0
5-6
7-8
9-10
furlongs
11-12
>13
0.6
0.5
0.4
0.3
0.2
0.1
0
5-6
7-8
9-10
furlongs
11-12
>13
0.6
0.5
0.4
0.3
0.2
0.1
0
5-6
7-8
9-10
furlongs
11-12
>13
0.8
3-year-old race distances
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
5-6
7-8
9-10
11-12
furlongs
13-14
15-16
What is a C:C ?
•
•
•
•
Average best race distance – 6.5 f
75 % 5 f winners are C:C
65 % 6 f winners are C:C
98 % of C:Cs win ≤ 8 f
• FAST, SPEEDY, SPRINT TYPE
≤8f
What is a C:T ?
•
•
•
•
Average best race distance – 9.1 f
Almost 70 % C:Ts win ≥ 8 - 12 f
50 % C:Ts win ≤ 8 f
55 % of 12 f winners are C:T
• FAST, MIDDLE-DISTANCE TYPE
7 – 12 f
What is a T:T ?
•
•
•
•
Average best race distance – 11.1 f
> 90 % T:Ts win ≥ 8 f
> 80 % T:Ts win ≥ 10 f
No 5 f or 6 f winners are T:T
• EXHIBITS STAMINA
>8f
Optimum genetic profile for distance
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
5
6
7
8
9
furlongs
10
11
12
>13
Quarter Horse – speed
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
C:C
C:T
T:T
Egyptian Arabian – stamina
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
C:C
C:T
T:T
Thoroughbred (Flat) – speed & stamina
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
C:C
C:T
T:T
1
Thoroughbred (National Hunt) – stamina
0.9
0.8
0.7
0.6
0.5
0.4
0.3
There were no
C:Cs among 32 NH
winners in a
prominent Irish
NH yard
0.2
0.1
0
C:C
C:T
T:T
Practical Applications
1. Young stock (foals and yearlings)
Make informed selection and sales decisions
2. Horses-in-training
Reduce operating costs and fine-tune racing strategy
3. Broodmares
Optimise breeding outcomes
4. Stallions
Promote stallions potential
Young stock (foals and
yearlings)
Make informed selection and sales decisions
• Establish achievement of breeding goal
• Identify speedy individuals and early two-year-olds
• Identify middle-distance individuals with speed
• Identify longer distance individuals with enhanced stamina
T
T
C
CT
CT
T
TT
TT
T
T
T
TT
TT
T
TT
TT
This is an example only
C
T
C
CC
CT
T
CT
TT
This is an example only
C
C
C
CC
CC
T
CT
CT
This is an example only
C
C
C
CC
CC
C
CC
CC
Horses-in-training
Reduce operating costs and fine-tune racing strategy
• identify most precocious two-year olds
• train and race for optimal racing distance
n = 142 two-year-olds in training with same trainer 2007 & 2008
n
CC
CT
TT
40
67
35
total no.
no. runners races won
21
32
13
17
26
6
% winners
to runners
% wins to
runners
mean no.
races per
runner
52.4
56.3
46.2
81.0
81.3
46.2
4.1
3.6
3.1
no.
total
mean
earners >
earnings (£) earnings (£) £100k
511k
1801k
87k
20k
36k
5k
1
5
0
• As two-year olds C:C and C:T horses outperform T:T horses
• C:C and C:T horses earn up to 13-times more than T:T horses as two-yearolds
• C:C two-year-old colts have 7% more muscle mass than T:T two-year-old
colts
n = 41 two-year-olds in training with same trainer 2007 & 2008 by a single sire
n
CT
TT
22
19
total no.
no. runners races won
12
9
18
5
% winners
to runners
% wins to
runners
mean no.
races per
runner
75.0
55.6
150.0
55.6
3.8
2.6
no.
total
mean
earners >
earnings (£) earnings (£) £100k
1620k
67k
73k
3k
6
0
Broodmares
Optimise breeding outcomes
• focus on optimal breeding mares
• select compatible stallions
• mix and match mares and stallions to fine-tune breeding goals
Mix and match matings to suit
breeding goal
Mating
Progeny
C:C on C:C
100 % C:C
C:T on C:C
50% C:C 50 % C:T
T:T on C:C
100 % C:T
C:T on C:T
25 % C:C 50 % C:T 25 % T:T
C:T on T:T
50 % C:T 50 % T:T
T:T on T:T
100% T:T
Stallions
Promote stallion potential
• predict stamina index for young stallions (5 year advantage)
• attract compatible mares to enhance stallion profile
Stallion Stamina Index
Who can use the Equinome Speed
Gene Test?
•
•
•
•
•
•
Bloodstock agents
Owners
Commercial breeders
Owner/breeders
Trainers
Pin-hookers
• The Equinome Speed Gene Test is available in Ireland and is also
available to the global bloodstock industry
What are the benefits of the
Equinome Speed Gene Test?
• Reduce risk
• Minimize operating costs
• Maximize return on investment
• Improve strike rate
Sample Submission
• Provide 4-5 ml uncoaggulated blood sample (purple cap K2-EDTA tube)
per horse
• Clearly label tube
• Complete Sample Submission Form
• Results returned within 3 weeks of receipt of sample
EQUINOME Laboratories
UCD Veterinary Sciences Centre
University College Dublin
Belfield, Dublin 4
Ireland.
tel: +353 (0)1 716 3775
www.equinome.com
Thanks to...
•
•
•
•
•
UCD School of Agriculture, Food Science and Veterinary Medicine
NovaUCD Innovation and Technology Transfer Centre
Science Foundation Ireland
Glebe House office and yard staff
Irish Thoroughbred Breeders’ Association
• Owners, breeders and trainers for willingly and generously
providing the crucial samples for the research project.
"The introduction of genetic know-how to breeding will dramatically change the
face of the bloodstock industry. We have begun and intend to continue to utilise
this highly valuable tool to fine-tune decision making in our operation. This will
fundamentally change the way we will have to think about breeding in the future.“
John O'Connor MRCVS, Managing Director, Ballylinch Stud, Ireland
"I found your findings fascinating, and highly credible in that they tally with what
we have learnt during many years practical experience. Having this information
available before the event is sure to provide users with an edge.“
Kirsten Rausing, Chairman, The Thoroughbred Breeders' Association (Great Britain)
www.equinome.com