Centre for East African Running (2004, Glasgow)


Glasgow University Symposium Possible Causes of Success of East African Distance Runners March 8, 2004.

Keith Johnson – genetics dept

‘Off the track, in the field’ Yannis Pitsiladis

Dr. Bezabeh Wolde, Sec Gen Ethiopian Olympic Committee

Sampled entire Olympic team Team trains together

Kotebe College of Teacher Education, Addis Most of athletes from Shewa and Arsi (central part of Ethiopia) -    altitude 3000m (Addis Ababa is 2400m) Bekohi, Aris Province -    deratu tulu -    kenenisa bekele children’s journeies to school by foot/running/cycling World Champs Paris, 10000m -    gold, silver, bronze all Ethiopian

Kenyan First Olympic Gold – Neftali Temu, Mexico Olymmpics Mike Boit, bronze medal 800m 1972 Munich, Olympics Commonwealth Gold, Edmonton, 1978 Nambi? Nandi? province Rift Valley St. Patrick’s High school – boys school -    many Olympians from here tea break – important? Itigo Girls High School Pupils running to school Morning, for lunch, and afternoon (parents must find food for them) Kaptagat Training Camp – Patrick Sang -    Global sport sponsorship -    Joseph Chelimo, Head Coach -    Eliud Kipchoge – gold 5000m World Champs, Paris 2003 -    Richard Limo – Gold 5000m, Edmonton 2001 -    Camp has no electricity -    Cooking fone in pots

IOC Consensus Statement on Sport Nutrition 2003 All cooking done on fires, very precisely

Daily diet -    average carbo 606g -    body weight on average 58.6 -    near perfect ratio

Fluid intake

Eliha Lagat (boston marathon)

IOC Camp – Kipchoge Keino (most well known of Kenyan athletes)

Chirchir training camp -    sampled athletes -    tea important again -    ran in morning without breakfast, and return to have tea with 3 slices of bread

Chepkoilel Stadium Kaptagat Camp (FILA) -    moses tanui -    unpasteurised milk for tea

Amos Biwott (3000m gld, Mexico 1968)

Fatwell Kimaiyo Gold 110m 1976, hurdles

Commonwealth games perth 1962, seraphina antao, gold

“whether there is money in it or not, running is in the children’s blood” school teacher

Acknowls John robertson bequest, uni of glasgow EOC, EAF, Wellcome Royal Soc Carnegie Scotland Event sponsored by Glasgow City Council, Abgene, WWR International, Cranlea

Used Bleep test – had not heard of this test before. -    results under analysis -    1000 kids tested in Nairobi

no obese kids in nandi, but plenty in nairobi

agali (staple part of diet) -    similar structure to rice

John Bale

Pre-colonial period Cultures of running Myth of natural athlete

FAM Webster arranged comp between spear throwing and javelin

Modern period When running became racing Refute idea that these Kenyans emerged in 1972 from nowhere those performances had roots in 1900s earliest recording sportised event was in 1902 one of first timed events – modern notin of recording

influence from Muscular Christianity through missionaries 1924 bureaucratisation of Kenyan running organised African Olympics records from the 1930s best performance for mile measured to second 1951 formation of African Amateur athletic federation

joy adamson – anthropoligist, research on athletic body, Masai

1954 kenyan began to engage with international comp, NOT 1968 Mexico Olympics

Kenyan Olympics, won medals in high jump, javelin, and sprinting Diversification of athletic production imp At Vancouver Empire Games, team was 2 runners in 440m, 1 in 880m, 1 in 3, 6 miles, … -    no suggestion that this was a running team at all went on into 1960s

present time… -    how does this history help explain Kenyan running? -    Need to take a global perspective -    Can Kenyan running be partly explained by the absence of success in the West -    As West declines in interest in this kind of activity, for various reasons – range of alternative activities, which has led to diminution of people taking part in long distance events. In part, this explains the success of Kenyans. -    There are poor results in these events in the west Has slope in improvement of these records declined? Things are slowing down in those events in the west

Interesting to examine how Kenyans react to this running phenomenon and how Kenyans view the western view of this -    neo-colonialism -    need a Kenyan voice

mtDNA Haplotypes and Demographics f Elite Ethiopian Athletes Robert Scott

Why do some people perform better than others?

Proposed explanations for greater success -    favourable physiology -    altitude adaptation -    running long distances to school -    psychl advantage (and cultural = ME: but actually doesn’t mean this) -    favourable genetic endowment

believes tha genetics is important, but not in way that people have considered

Majority of human genetic diversity is within populations rather than between -    more within East Africa than in Europe

more than skin colour needs to be considered -    ok, so what then?

Ethiopia

Methodology

Enviro analysis -    place of birth -    language -    distance and method of travel to school

genetic analysis: mtDNA -    mitco are major energey producers -    mito function imp in ex

mtDNA useful in population genetics -    maternal inheritance: no recombination -    fast mutation rate (D-loop) -    Maternal ancestry can be traced through branches of tree

MtDNA genome separate from

Buccal swabs from 109 control and 114 elite athletes MtDNA extracted and classifieid -    HVS-1 polymorphism -    Coding region polymorphism

Compare distrib of mtDNA types amongst athletes and controls

Ethiopian Regions -    arsi is over-represented in succeses

Place of birth results

Slightly more from Assis Ababa for elite athletes Large increasee for 18%

Might show that athletics is more prevalent in Arsi

Language Results

Possible that different ethinic goups have different frequencies of gene variant

Might be to do with popularions

Distance travelled to school results

Evidence that this might be influential

Students running some 5-10km to school, and even some running marathon distances.

MtDNA questions -    if mtDNa polymorphisms are imp in endurance performance, will t linage on whch they occur be more common amongst t athletes? -    Might this explain t dominance of East African athletes in distance running?

Contrls’ mtDNA tree -    Mitochondrial Eve

Athletes’ mtDNA tree -    relatively similar distribution -    not significantly different

Conclusions -    Ethiopians are of a distinct enviro background relative to Ethiopian popn -    Athletes have a very deep common maternal ancestry -    Athletes are not a genetically distinct population as defined by mtDNA

How does the ACE I/D polymorphism affect athletic performance, especially in East African athletes? Richard Wilson, Molecular Genetics, IBLS, Glasgow University of Paisley

Why t ACE gene? -    is a major target for blood pressure controlling therapies, and has other less well-understood activities

Why geontype athletes? -    athletes with extremes of physiological performance may help elucidate t physiological variation of normality

why genotype Africans? -    African populations contain more genetic variation than European-derived populations

What does ACE I/D do?

Lots apparaetly -    publications showing effects ranging through, o    – muscle performance in response to training skeletal muscle fibre type (in young Japanese), endurance performance (UK Olympians), high altitude adaptation, survival to 100yrs old (in France); kidney responses, insulin sensitivity, etc

How does ACE (I/D) do all this?

ACE -    activates Angiotensinl to AngiotensinII (which raises blood pressure) -    inactivates Bradykinin (removing a factor which lowers blood pressure) -    Two ACE activities so far, is it all this simple?

ACE is DCP1

ACE is a dipeptidase, cutting two amino acids off peptide hormones -    angiotensiI DRVYIHPF HL -    Bradykinin RPPGFSP – FR -    Haemoregulatory peptide AcSD – KP

Ace is an enxzyme that clips other peptide hormones

High affinity for hameo

Ace is found attached to endothelial cells and soluble in blood plasma Form of ACE is found in sperm -    In mice, where have engineered out sperm type, but not other, sperm no longer functions properly, no longer capable of fertility -    Link to cleaning vaginal secretions, which kill sperm (possible fertility link)

Functional genomics of the human ACE / DCP1 gene -    t full ACE protein has two active sites -    33 ACE isoforms o    som – DCPi – link – DCPi – anchor o    som – DCPi – link I DCPii o    tes – DCPii – anchor (male form)

ACE can do a range of things and is collecticated

Variations in the Human ACE gene -    over 70 common variants (SNPs) in 30000 DNA bases of human ACE Gene -    less than 10 of these ACE SNPs chang t functioning of the ACE gene -    human ACE gene shows t signature of recent natural selection (haplotypes / linkage disequilibrium) -    The famous ACE I/D polymorphism is almost certainly non-functional o    Is in region of gene that is removed

The ACE I/D polymorphism -    is easy to test for -    in Caucasians, ACE I/D is associated with 40% of opulation variation in circulating ACE levels (I low, D high) -    Is ace I/D hitch-hiking with t real functional change? (haplotypes) -    if look for other markers on ACE gene, knowing that how different versions have been shuffled around 22982AG is t best functional candidate, I is always found with 22982A in Caucasians, D with 22982G

DNA sampling at Kaptagat Training camp -    sample using swabs -    can diagnose people’s genotype, to carry out genotyping

An ACE blood sampler -    removed from Kenyan population, -    Kenyan, no longer regulated in same way that they are in Caucasians

ACE I/D PCR -    Extract DNA, and amplify small pieces of it

Can genotype for most markers in the ACE gene -    Roberts and others have set-up assays

ACE activity and I/D -    ethio: 40% variation -    Kenyan: 7%

ACE activity and 22982AG -    real causative agent for circulating ACE levels

Conclusions -    22982AG (not I/D) is t functional polymorphism regulating circulating ACE levels -    Kenyan / African population genetics have modified t assoc between ACE i/D and 22982AG

Few people who came out of africa historically, cold not carry the level of variation that existed in Africa -    expains why we do not see this variance in other locatioes

Is ACE I/D asoc with excelenct in Ethopian -    genotyped 114 (… -    no strong assoc with ACE I/D or 22982AG

Ethiopian ACE/ID data -    not clear that ID is solution for talent searching.

ACE I/D might work differently in males and females

Little effect of ACE ID and other polymorphisms on elite endurance Cannot use it as predictive test, May subtly affect training response Tell everyone they’ve got the ACE gene (placebo effect)!

Any evidence that ACE gene involve with other aspect of performance

Best studies are small groups of people, where have looked at small aspects of physiology , rather than assoc with large athlete cohorts.

Y Chromosome haplotypes and the African endurance Athlete Colin Moran

Overview Existing theories (including genetics) Why Y? -    what is t Y chromosome? -    Y chromosome consortium YCC) tree -    Global distrib

Techniques and subject groups Analysis -    by major clades -    by haplotypes

In the beginning -    Rome Olympics, 1960s -    Atlanta Olympics 1996 -    Sydney Olympics 2000 -    37 of top 40, 10k times

Explanations for Success -    diet -    culture -    genetics o    mtDNA o    ACE o    Alpha-actinin 3 (ACTN3) o    Y chromosome

Now around 100 genes associated with human performance

Human Karyotype -    picture of chromosomes -    23rd ppair of chromosomes are sex chromosomes (smallest) why Y? -    patrilineal inheritance -    never 2 y’s in 1 cell o    functional changes immediately subject to selection o    no recombination

haploid (because only one copy of it)

different types of y chromosome in different proportions around the world, because it is a dynamic chromosome

Summary -    Group analysis: o    Control groups not different o    Some difcs between athlete groups and control groups

-    indiv haplotype anaylsis o    4 haplotypes showed as o    sev haplotypes that we may have expected to showed no assoc •    African specific clades, A and B •    E3b*/E3b4 similar to E3b1 •    J(xJ2) which had apparent

Conclusions -    some Ethiopian Y haplotypes show assoc with elite athletes status, though not really a predictor -    Athletes are more distinct from the Arsi control population than the Addis control o    Arsi control truly representative? •    Town v country?

-    how can t y be having such an effect? o    Direct effect of a gene on the Y chromosome o    Unknown subgroup of the population?

Thanks LeicesterUniversity of Paisley    - mark jobling

Demographic characs of elite Kenyan endurance runners Vincent Ochieng Onywera

The Kenyan Runners: In search of Olympic Glory Mike Boit, Kenyatta University

Olympic boycotts and lack of exposure, performance in Kenya declined significantly

Top runners left or stopped

Kenyan Athletes in top ten of world 1968-72: 1 73-76: 4 77-80: 3 81-84: 1 85-88: 4 89-92: 9 93-96: 6

we are still not at human potential in sport – still not training enough

set backs -    inadequate facilities -    less than minimum sports funding -    lack of sophistication in coaching -    lack of expertise in nutrition -    lack of institutional training -    lack of systematic talent identification plans and implementation programme

CULTURAL traditions -    cattle radigin expedition practices (hugh demand for endurance), suallly taken as sports for the young warriers -    male circumsision (process of instilling high discipline, agresiveness, etc; ability to withstand pain)

would be prudent to assist athletes in providing alternative to taking drugs that could enhance their performance