Genetics in Sports

1
Genetics in Sports

• Dr. Ead Lorprayoon
• Faculty of Medicine
• Chulalongkorn University

2
Michael Phelps
Olympic medal record Olympic medal record Olympic medal record
Competitor for      United States Competitor for      United States Competitor for      United States
2008 Beijing - Men's Swimming 2008 Beijing - Men's Swimming 2008 Beijing - Men's Swimming
Gold 400m individual medley 403.84 (WR)
Gold 4 x 100m freestyle relay 308.24 (WR)
Gold 200m freestyle 142.96 (WR)
Gold 200m butterfly 152.03 (WR)
Gold 4 x 200m freestyle relay 658.56 (WR)
Gold 200m individual medley 154.23 (WR)
Gold 100m butterfly 50.58 (OR)
Gold 4 x 100m medley relay 329.34 (WR)
3
Wing span 6 ft 7 inches
Torso Man 6 8
Height 6 ft 4 inches
Leg Man 6
4
Broad Shoulder Slim Waist
Big Hands
5
Double-Joint Elbow - Knee Ankle- Feet
12,000 calories /day
Giant Feet Size 14
6
(No Transcript)
7
(No Transcript)
8
Olympic Gold begins with good Genes ?
9
Kinesiogenomics

• The Study of
• Sports and Exercise Genetics

10
(No Transcript)
11
Deoxy Ribo Nucleic Acid
12
History

• 1953 Discover DNA by Watson and Crick
• 1970 - Genetic research in human sport and
  exercise started
• 1997 - First major textbook written by Claude
  Bouchard et.
• 2007 - Introductory level textbook on sport and
  exercise genetics by Roth

13
How scientists study genes ?

• Quantitative genetics
• Heritabilities
• Statistical analysis

14

• Linkage base studies
• Gene on Chromosome
• Candidate gene analysis

Growth of candidate gene and linkage based
studies on erformance and fitness related health
phenotypes
15
How genes effects Physical Performance ?
16
Phenotypes and Genotypes
17
Genes determine Respond to exercise Training,
Diet, and other Environmental factors.
18
Specific genes and Physical Performances
19
Finnish cross-country skier
Eero Mäntyranta

• 1960 and 1964 Olympics
• 3 Olympic gold medals
• 2 World championships.
• 30 years later,
• 200 of his family tested
• 50 including Mäntyranta
• a rare mutation in the gene HCP (Hybrid Cluster
  protein) that produces the receptor for the
  hormone erythropoietin (epo).
• Hematocrit gt 50 would be disqualified.

DOPE ?
20
Questions about Jamaican Sprinters ?

• Jamaica a small island
• more Olympic medals than countries many times
  its size and wealth.
• 2008 Olympic Jamaica has
• 4 fastest women at 200 M,
• 4 of the top 6 at 100 M
• The fastest man 100 m

Shelly-Ann Fraser
21
Usain Bolt
Medal record Medal record Medal record
Competitor for      Jamaica Competitor for      Jamaica Competitor for      Jamaica
Men's athletics Men's athletics Men's athletics
Olympic Games Olympic Games Olympic Games
Gold 2008 Beijing 100 m
Gold 2008 Beijing 200 m
Gold 2008 Beijing 4 100 m relay
22
An International Centre for East African Running
Science (ICEARS) Established in Glasgow

• Preliminary findings
• 70 Jamaicans habitants have the ACTN3 gene
  version that produce Actinin-3 protein
• 28 of Jamaicans are heterozygous for ACTN3
  gene,
• which has the same effect but to a lesser
  degree.
• The rest have the null form of the gene that
  produces no protein at all.
• Australians only 30 per cent were found
  with the speed protein Actinin-3
• At least one billion people worldwide must be
  completely deficient in Actinin-3

23
ACTN3 Gene and Actinin

• ACTN Gene
• encode forming of actin binding proteins
  Actinins
• Actinins
• stabilize Actin filaments stronger
  contractions
• Two main types of
• ACTN gene ACTN2 and ACTN3 Actinins type 2
  and 3
• ACTN2 is expressed in
• all muscle fibers
• ACTN3 is only in
• fast twitch fibers.

24
Actin
Myosin
25
Chromosome 11
26
(No Transcript)
27
The Human Gene Map for Performance and
Health-Related Fitness Phenotypes The
2006-2007 Update

• The fitness and performance map now includes 214
  autosomal gene entries and quantitative trait
  loci plus seven others on the X chromosome.
• There are 18 mitochondrial genes that have been
  shown to influence fitness and performance
  phenotypes.

28
(No Transcript)
29
Insulin-like Growth Factor ( IGF-1 )
and Myostatin
The lean, double-muscled Belgian Blue Bull
breed a Mutated form of the Myostatin gene
(Sweeney, 2004)
30
Repair of Muscle Injuries

• Satellite cells proliferate around the wounded
  fiber to help the repair process
• IGF-1 partly controls the building and repair
  of muscles by stimulating the proliferation of
  satellite cells.
• Myostatin has the opposite effect, halting the
  proliferation of satellite cells.

31
The leg muscles of mice treated with IGF-1
(right) are bigger than the leg muscles of
untreated mice (left).
32
"Marathon Mouse 2004"
Gene PPAR-Delta
Peroxisome proliferators-activated receptor

• Run twice as far as normal mice
• Run 1 hour longer than the average 90 minutes a
  normal mouse
• Increase - slow - twitch muscle fibers
• Decrease - fast - twitch fibers
• Increase in fat burning in adipose tissues
• Gene PPAR-Delta regulates the expression of
  several other genes and ultimately enhances
  slow-twitch muscle fibers

33
Does Genethe only effect onPhysical Performance
?
34
You can never make a donkey to a race
horse...thats why genes matter when it comes to
sport. But By training you can make a slow
donkey to a faster one , Lee
Sweeny, Geneticist
35
Your past forms you , whether you like it or
not. Each encounter and experience has its
own effect , and youre shaped the way the wind
shapes a tree on a plain.
Lance Armstrong 2000
36
Environmental effect on physical performance
.The Training part
37
Usian Bolt among Jamaican athletes

• Usain Bolt
• lined up against athletes who almost certainly
  all express Actinin-3
• it cant possibly explain the astonishing
  advantage he has over his competitors.
• There must be other factors at work.

38
World record time womens marathonSince 1960
Decreased more than 1 hr
Elite athletes may be born with a favorable
genetic , but to realize athletic potential
requires years of focused training. Training is
itself a kind of self-imposed environmental
exposure, and when gifted athletes train this
could be considered an example of
geneenvironment correlation. The effects of
training on performance variation can be dramatic.
39
Elite athletes are those who respond in
extraordinary ways to training in order to unlock
an already present potential.
40
Making of a Champion

• Genes
• Effects Training
• G x E interaction
• G and E correlation

41
Environmental effects

• Pre-conception Gametic imprinting
• DNA methylation and Epigenetic effect
• Maternal diet DNA methylation and affected
  health and longetivity in mice offspring.
• Fetus
• Affected long term sequence
• Suboptimal fetal nutrition programs fetal
  metabolism with lifelong consequence.
• Birth weight and DM, Hypertension
• Baby with small for gestational age Fatter and
  less lean tissue mass.
• Fetal stress Irreversible metabolic change

42
During Infancy , childhood and adolescence

• Few researches during this period and Need more
  studies.
• Traits Reversibility
• Activity patterns and increased calcium intake
  during childhood and adolescence relate
  positively to bone mineral density in adulthood
• Gains in bone mineral density disappear at 1836
  months follow-up in calcium supplemented children
• In European children migrant to high altitude in
  South America,
• early exposure to hypoxia is associated with
  higher VO2 max and larger total lung volume
• Evident from early life (12 years of age)
  through adolescence, and are retained in adults.

43
Genetic EngineeringGene TherapyGene
TransferGene Doping
44
Genetic Engineering

• Process has five main steps
• 1. Isolation of the gene of interest
• 2. Insertion of the gene into a transfer vector,
  or carrier (e.g. virus, bacteries)
• 3. Transfer of the vector/carrier to the
  organismto be modified
• 4. Transformation of the cells of the organism
  (e.g. virus multiplies)
• 5. Separation of the genetically modified
  organism from those that have not been
  successfully modified

45
Gene Therapy

• Introduction of a normal gene into an
  individuals genome in order to repair a mutation
  that causes a genetic disease .
• Technique is Gene transfer.
• 2 Ways of Therapy
• In Vivo
• Ex Vivo

46
IN - Vivo Gene Therapy
47
EX - Vivo Gene Therapy
48
(No Transcript)
49
Risk Complications Gene Doping

• 1999 Jesse Gelsinger (18) died from immune
  response to the virus vector.
• X-linked hemophilia patients with gene therapy
  developed leukemia.
• Gene EPO in monkey make blood thrombosed and
  Anemia in some (immune attacked EPO)
• Virus vector can infect other human (viral
  shedding)
• Improper used of Gene , like improper use of
  anabolic steroid

50
World Anti-Doping Agency WADA
51
Laboratory Detection of Doping
Elite sport has entered the world of forensics,
where winners and losers of competitive events
can be declared in the courtroom, not the playing
field
52
Tests to detect Gene Doping

• A biopsy of suspected muscle tissue
• Suspicious elevations key biologic substances
  that indicate gene doping by serial monitoring of
  blood parameters.
• Detect abnormal gene activity uses cutting-edge
  microchip gene array technology or nanotechnology
  breakthroughs
• A protein fingerprint or a genetic map of
  the biochemistry of individual athletes
• Genetic barcodes

53
Genetic Tests
54
Ethics
55
Investigation of Differences between human
populations.Racial discriminations ?
Potentially problem
56
Differences between genetic and non-genetic tests

• Unanticipated disease links seems Higher for
  genetic tests than for other biomedical tests
• Human DNA cannot be modified to mitigate
  associated risk
• Genetic performance test conducted on an embryo
  will yield the same information as a genetic test
  performed on an adult.

57
Who should be allowed to request ?

• People for themselves
• Coaches to Athletes to select the team
• Parents to Minors and Embryo
• pre-implantation genetic information on embryos
  in order to select the best sport genotype
• post-implantation data and consider aborting the
  foetus if the wrong genotype for sport is
  discovered
• Insurance company to their clients.

58
World Anti-Doping Agency, 2005

• The use of genetic information to select for or
  discriminate against athletes should be strongly
  discouraged.
• This principle does not apply to legitimate
  medical screening or research

59
Recommendations (For Now)

• Adults request genetic performance tests on
  themselves
• Only at the request of the individual who will be
  tested
• Should be counseled before the test
• Confidential to the tested participant, with only
  that individual making decisions based upon such
  information
• Restrictions imposed on young people on the basis
  of an assumption of lower mental capacity than an
  adult.
• Ban antenatal genetic testing for sport related
• traits and consider such a ban also to protect
  children.

60
Conclusion

• Not only gene affect phenotype for physical
  performance but also how people can respond to
  environment.
• Environment has effect early in embryo and mostly
  in fetal life and also in adolescence.
• Gene and environment interact over the lifetime
  of an individual with permanent effects on the
  adult phenotype.
• Champion comes with good gene and appropriate
  training.
• We now know many genes that effect performance
  both aerobic and anaerobic exercise.

61

• Gene can be engineering, transferring , curing
  and doping ?
• Researches are ongoing and some inappropriate
  ones may be unnoticed.
• Gene test should be only for an adult for his or
  her own merit.
• Confidential only to the test participant is
  crucial.
• Gene doping and research for gene doping should
  be banned.

62
The End
Thank You