Lecture 23- Genetics and Sport

Question 1

What are some of the thoughts about sports and genes?

Answer 1

• best sprinters are almost exclusively of West African descent
• tests to see of the

Question 2

What are some of the questions?

Answer 2

Can you:

• ask questions about a genetic test already taken and realted to sport when person applies for job; or to participate in sport
• ask a person to take a genetic test
• require them to take a test before employment
• child?
• is it different for test to show they will be good at that sport? Or protect them from harm?

Question 3

What is the issue with genes and sport?

Answer 3

1. Relevance of genetic test results for sport
2. Are genetic tests banned for employment in sport? NO.
3. Can sports participants be required to have a genetic test before being allowed to participate in a match? NO, probably.
4. If gene doping was possible, should it be made an offence in competitive sport?

Question 4

What is the relevance of genetic test for sport?

Answer 4

• NHMRC Use of genetic information in sport:
• lack of evidence of benefit of testing above other means of assessing talent
• potential discrimination
• possible physical and psychological harm to child if test results misinterpreted
• AMA, genetic testing 2012 (Position Statement) advises against direct to consumer test w/o proper counselling

Question 5

What is the connection between genetic test results and sport?

Answer 5

• strong genetic basis for human physical performance and elite athlete status
• endurance, power, response to training
• other factors that determine success include: epigenetics, environmental influences, such as training, motivation, nutrition, advances in equipment etc.
• NB genetic studies often not conclusive and at times contradictory -small numbers, heterogenous populations (gender, ethnicity, sport discipline)

Question 6

Are genetic tests banned for employment in sport?

Answer 6

• No, as long as the person consents to get the test then it is lawful
• the issue is that they are “pressured” to reveal this information as they want to be employed
• eg. Vic 2001: proposed that professional boxers be tested for gene mutation making fighters punch drunk, test intended to protect employees

Question 7

What decides what is reasonable?

Answer 7

What is reasonable will depend on the relevance and accuracy of the particular genetic factor in predicting success or other outcome

Question 8

Where can you complain to?

Answer 8

• Australian Human Rights Commission

- Victorian Human rights and equal opportunity commission

Question 9

Can sports participants be requires to have a genetic test before being allowed to participate in a sport?

Answer 9

• free, voluntary and informed consent is generally required before a medical procedure is performed
• this includes information about material risks : Rogers v Whitaker
• but is it possible for a person to make a free and voluntary decision if the test is “required” to participate in a sporting activity?

Question 10

If gene doping was possible, should it be made an offence in competitive sport?

Answer 10

• YES:
• level playing field
• inequities between those who can afford it and who can’t
• possible risks for athletes
• prohibit it to make a statement of community views
• NO:
• impossible to enforce a ban
• inevitable inequities
• may help treat injuries
• novel, but not likely to be widely used

Question 11

What is true of muscle fibres in athletes?

Answer 11

“…the muscles an individual has inherited genetically determine, to a large extent, the type of sport played…”
“…Marathon runners, long-distance swimmers and other endurance athletes have a greater proportion of slow-twitch fibres in their muscles, while sprinters rely on fast-twitch muscles…”
-“…an athletes explosive ability - how quickly their muscles can generate maximum power - is also inherited with their other genes but can be enhanced through training…”

Question 12

What are the aspects that affect an elite athlete’s performance?

Answer 12

-training, drugs, psychology and genetics

Question 13

What is the heritability of major determinants of anaerobic performance?

Answer 13

Cardiorespiratory
 Endurance phenotype (25-66%)
 VO2max response to aerobic exercise training
ranges from 5-88% (Gagnon et al. 1997)
 Oxygen-carrying capacity of blood
Neuropsychiatric (?)
 The “mongrel factor”
 Endorphin response : motivation

Question 14

What about the heritability of the muskoskeletal components in anaerobic performance?

Answer 14

 muscle mass
 fibre-type proportion (close to 100%)
 activity of glycolytic and oxidative enzymes (50%)  speed and tempo of movements
 force-generating capacity of type 2 fibres
 capacity to adapt to exercise training (60%)

Question 15

Can you isolate genes responsible for these factors?

Answer 15

• The human genome project has identified 20-25,000 human genes
• Genes are recipes for specific proteins
• Many genes are found in different versions in the
general population (polymorphisms)
• Different version of a gene can influence normal
variations in muscle performance and strength
• Genetic association studies examine whether some
of these versions are found more frequently in one group than another, e.g. athletes vs controls

Question 16

What are the genes that have been associated with elite athlete status?

Answer 16

-Elite athlete status:
– Angiotensin-converting enzyme (ACE) – α-Actinin-3 (ACTN3)
-Cardiorespiratory function:
– Angiotensin-converting enzyme (ACE) – β2-adrenergic receptor (ADRB2)
– PGC1α (PPARGC1)
-Skeletal muscle function:
– α-Actinin-3 (ACTN3)
– Ciliary neurotrophic factor (CNTF) – CNTF receptor (CNTFR)
Susceptibility to head injury
– Apolipoprotein E (APOE)

Question 17

What do the alpha actinins do?

Answer 17

• ACTN3-component of muscle fibre

- alpha actibins are in teh Z line, where the nabds cross, in contraction of the myofibre

Question 18

What are the types of alpha actinin in skeletal muscle?

Answer 18

• alpha actinin 2 and 3
• close relatives
• the 3 one is specialised for sprinting (in fast muscle fibres)

Question 19

What is the gene case with ACTN3 in the population?

Answer 19

• common polymorphism in the ACTN3 gene, normally at position 577 the amino acid is arginine which leads to ACTN3 in fast fibres
• but an extra stop message, so the protein is not there
• quite common in general population (25% don’t have the gene), this influences muscle performance
• 1.5 billion people worldwide are deficient

Question 20

Does α-actinin-3 deficiency affect muscle function in humans?

Answer 20

• it does! genetic predisposition if power or strength performance
• knew it wasn’t associated with disease as normal people have it
• so did a study to see
• ACTN3 genotype is associated with muscle performance in non athletes
• hypothesis that if deficient in ACTN3 (only occurs in fast muscle fibres) then detrimental to sprint performance= this turned out to be true
• in endurance athletes there is a tendency to have more ACTN3 deficiency
• the ones not having ACTN3 tend to be weaker and slower

Question 21

How did the law reform commission take this??

Answer 21

• Essentially Yours – a report by the Australian Law Reform Commission published in 2003
“…if the AIS were to use genetic information to select athletes, it would be necessary to ensure that the information was reasonably reliable and relevant. If not, it would be possible to argue that the information was being used to discriminate unlawfully against individuals…” (page 963)

Question 22

So is ACTN3 reliable and relevant?

Answer 22

• ACTN3 XX genotype – less likely to excel at an elite
level in 100m sprint
• ACTN3 genotype indicates a genetic predisposition for sprint vs endurance traits but its positive predictive value is unknown
• There is no evidence that ACTN3 is a good predictor of performance in sports requiring more than just physical strength, e.g. teamwork, hand-eye coordination, reflexes, tactics…
-It is unclear whether testing ACTN3 would provide any advantage over existing tests of muscle performance (e.g. vertical jump, sprint times)
• At this stage ACTN3 testing has not been shown to be a “reliable and relevant” indicator of performance in most sports

Question 23

How does α-actinin-3 deficiency influence the function of skeletal muscle?

Answer 23

-the actinin 2 can partially compensate for the actinin 3
-so have more actinin 2 (closely related)
• • •
KO mice are weaker than WT (still WNL) but can run for longer Mimics the phenotype of XX humans
The Actn3 knockout mouse provides a useful model to determine the function(s) of α-actinin-3 UNIB20007_SM1_2015

Question 24

What are fast fibres for?

Answer 24

Sprint/strength performance Generate greater force Susceptible to fatigue
 Contract and relax quickly Are larger
 Rely on anaerobic metabolism

Question 25

What are slow fibres for?

Answer 25

Endurance performance  Generate less force
 Resistant to fatigue
 Contract and relax slowly Are smaller
 Rely on aerobic metabolism

Question 26

Why is α-actinin-3 deficiency How does α-actinin-3 deficiency
detrimental to sprint and beneficial to influence the function of skeletal
endurance performance?

Answer 26

• KO muscles are slower to relax following contraction
• Less able to generate rapid repetitive contractions
-slower to keep twitching that you need for fast powerful movements
-Muscles lacking -actinin-3 have slower contractile properties
-alpha actinin 3 muscle is faster to recover

Question 27

What is the metabolism like?

Answer 27

-fast muscle fibres use glucose and produce lactata and slow use oxygen
-α-actinin-3 deficiency → shift in properties of fast muscle fibres towards a slow phenotype
• Slow” muscle characteristics of fast fibres would be detrimental to sprint and power activities
• Mimics properties seen following endurance training

Question 28

Does ACTN3 genotype influence response to training and performance?

Answer 28

 7 WT and 9 KO mice (replicated x3)
 4 weeks of forced treadmill running, 5
days/week - ~1.5km/day
 Training and testing performed active dark cycle; gradual increase in speed, slope and length of training.
 Endurance testing after 4 weeks of training, compared to age matched controls
-Greater improvement in endurance performance in KO mice

Question 29

The future?

Answer 29

What we want to avoid…
 “designer” athletes  “gene doping”
BUT …
 Complex phenotype - the effect of any one gene in isolation is likely to be small
(poor predictive power)
 100’s of genes involved - no “simple test”
-? Devising individual training regimes ID potential sprinters vs stayers Predict response (e.g. high altitude) Avoid fatigue
? Expand selection criteria and ability to identify “potential” athletes, i.e. who will respond to training
? Increased understanding of how muscles work