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2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

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Page 1: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

2013Marek Vácha

The future of customize medicine is in your DNA; don´t wait until you are sick to learn why.

Dr. Mehmet Oz

Page 2: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

DNA analysis

23andMe https://www.23andme.com/ Navigenics http://

www.navigenics.com/ deCODE http://www.decode.com/

Page 3: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

DNA analysis

23andMe https://www.23andme.com/ $ 399 spitting into special test tube

Navigenics http://www.navigenics.com/ $ 2499 spitting into special test tube

deCODE http://www.decode.com/ $ 985 scraping cells from a cheek by a swab

Page 4: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Your DNA sequence, properly encrypted, will soon become a permanent part of your electronical medical record

Collins, F., (2010) The Language of Life. Profile Books LTD. London, GB.

Page 5: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

For centuries, we considered ourselves to be healthy until symptoms of illness arose. Once diagnosed, correctly or not, we received standardized treatments. In accordance with this view, the human body was generally ignored untill something went wrong.

Collins, F., (2010) The Language of Life. Profile Books LTD. London, GB. p. 34

Page 6: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

We do not have a health care system; we have a sick care system!

Collins, F., (2010) The Language of Life. Profile Books LTD. London, GB. p. 58

Page 7: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

2013Marek Vácha

Page 8: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Convention for the protection of Human Rights and dignity of the human being with regard to the application of biology and medicine: Convention on Human Rights and Biomedicine. 1997

Chapter IV - Human genome

Article 11 - Non-discriminationAny form of discrimination against a person on grounds of his or her genetic heritage is prohibited.

Page 9: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome – Internal Universe

After many centuries of investigations we have built up an approximate understanding of at least the more accesible parts of our external Universe

...however, there is also a largely unexplored Universe within us about 1011 neurons and somewhere in the region of 1015

interconnections

Page 10: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 11: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Three Stage Approach

Page 12: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Whole-genom shotgun approachCelera Genomics

Page 13: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Public Consortium and Celera

Page 14: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Public Consortium x Celera GenomicsFrancis Collins Craig Venter

Page 15: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 16: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Genome Gallery

Page 17: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Galerie genomů

Page 18: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Genome Gallery

Page 19: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 20: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 21: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 22: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome Project

officialy beagan in 1990 the project involved 20 large sequencing

centers in six countries plus a host of other labs working on small projects

largely completed in 2003 the sequence of each chromosome was

carefully analyzed and described in series of papers, the last of which covered chromosome 1 and was published in 2006

Page 23: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Nuclear Genome and Mitochondrial Genome

Page 24: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome

Page 25: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome

Page 26: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Dna sequences that acode for proteins or give rise to tRNA or rRNA compose a mere 1,5 % of the guman genome there are 78 000 proteins in human body

If we include introns and regulatory sequences associated with genes, the total amount of DNA that is gene-related - coding and non-coding - constitutes about 25 % of the human genome

put another way, only about 6 % (1,5 % out of 25 %) of the lenght of the average gene is represented in the final gene product

Page 27: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 28: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Unique noncoding DNA pseudogenes gene fragments small noncoding RNA

the genes that produce small noncoding RNAs are a tiny percentage of the genome, distributed between the 20 % introns and the 15 % unique noncoding DNA

Page 29: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Dispersed repeats(Jobling, M.A., et al. (2004) Human Evolutionary Genetics. New York, Garland Science

Class Number of Copies in the Haploid

% of Genome

Lenght

LINEs 850 000 21% 6 000 – 8 000 pb

SINEs 1 500 000 13% 100 – 300 pb

Retrovirus-like elements

450 000 8% 6 000 – 11 000 pb

Copy DNA of Transpozons

300 000 3% 2 000 – 3 000 pb

Page 30: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Transposon movementcopy-and-paste

Page 31: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Retrotransposon movementcopy-and-paste

Page 32: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Transposable elements and related sequences make up 25% - 50 % of most mammalian genomes and even higher percentages in amphibians and many plants

the very large size of some plant genomes is accounted for not by extra genes, but by extra transposable elements sequences like these make up 85 % of the

corn genome!

Page 33: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 34: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome

nuclear genome 3200Mb

mitochondril genome

16,6 kb

euchromatin 2900-3000Mb

constitutive heterochromatine

200Mb

Page 35: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome

coding DNA 50 Mb (cca 1,5%)

regulatory sequences 100Mb (3%)

noncoding repetitive DNA

50%

number of genes cca 22 000

nuclear genome cca 22 000

mitochondrial genome

37 genes

Page 36: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Discrepancies between Chromosome Number and Sequence Lenght

Chromosome 21 is bigger than 22

Chromosomes 9,10,11 are also named in the wrong order

Page 37: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Dates of 2010

Fritillaria assyriaca 124 billion bp Polychaos dubia (single-celled amoeba)

670 billion bp

There is a wide range of genome sizes within the groups of protists, insects, aphibians, and plants

and less of a range within mammals and reptiles

Page 38: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Genomes of Bacteria and Archea

genomes are „compact“ genomes are correllated to metabolic diversity

Mycoplasma genitalium – lives inside of eucaryotic cells genome 580 000 bp., 517 genes

Streptomyces coelicolor – soil bactery with extremely complicated metabolical pathways genome 8,7 mil. bp., 7 846 genes

Page 39: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Genomes of Bacteria and Archea

large genetic diversity between species cca 15 % - 30 % of genes are unique to a

species! lateral gene transfer

Thermatoga maritima – lives in hot springs up to 80 Celsia with many Archea up to 25 % of its genes closely related to genes of

Archea ! transferes are realized by viruses, plasmids and

transpozons

Page 40: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Genomes of Eucarya

genes are generally orders of magnitude larger

exons are only few percent of the genome majority of the genome are „repeated

sequences“

Page 41: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Year 2001

approximately 50 organisms entirely or nearly entirely sequenced 10 archea E.coli Saccharomyces cerevisiae C. elegans Arabidopsis thaliana

Page 42: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Year 2010

1 200 genomes entirely sequenced 1 000 of bacteria 80 archeal genomes 124 eucaryotic species

Page 43: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

1980: one lab 1000bp a day 2000: one lab 1000bp per second, 24 hours

a day, seven days a week

first human genome: 13 years and cost $ 100 million

James Watson´s genome: four months (2007) for about $ 1 million

2010: 3 humans, each $ 4 400 2011: one day, $ 1000, cca 1000 persons

Page 44: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

2011

all exons: $ 600

Page 45: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Craig Venter´s Genome

3 millions SNPs 14 779 changes in protein coding regions

(SNPs) 20% never seen before

2020 change in protein sequence (nonsynonymous aminoacid substitutions) 12% predicted to disrupt function of proteins 11% in disease-causing genes

Page 46: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

There is no "The Human Genome" platonic´s idea of the ideal human genome

probably does not agree with reality

another marks should be invented for deletions and inzertions

Page 47: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

2010: Homo Neanderthalensishttp://news.bbc.co.uk/2/hi/science/nature/8660940.stm

Between 1% and 4% of the Eurasian human genome seems to come from Neanderthals.

Svante Paabo (pictured here with a Neanderthal skull) led the research effort

Page 48: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Sekvenování genomu neandertálce

Page 49: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

2010: Homo Neanderthalensishttp://www.eva.mpg.de/neandertal/index.html

The Neandertal Genome Project

Page 50: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 51: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Number of Genes

Mycoplasma genitalium – 480 genes probably 265 – 350 genes only are really

irreplaceable

Page 52: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Number of Chromosomes

Myrmecia pilosula 1 pair of chromosomes fern Ophioglossum reticulatum 630 pairs

of chromosomes

Page 53: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Genomics: biology is about informations!

Page 54: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 55: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

What does it mean to be a human? Why we act as we act?

Nature (Genes)Nurture (Environment) Developmental Noise

Freedom Philosophy

}} Science

Page 56: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

James Watson

” We used to think that our fate was in our stars. Now we know, in large part, that our fate is in our genes.“

Page 57: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Francis Crick

The development of biology is going to destroy to some extent our traditional grounds for ethical beliefs, and it is not easy to see what to put in their place.

Page 58: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Zdroj:http://www.cnn.com/video/#/video/us/2007/10/19/todd.saudi.schools.cnn

Page 59: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Zdroj:http://www.cnn.com/video/#/video/us/2007/10/19/todd.saudi.schools.cnn

Page 60: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 61: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

A Man: a Periodic Table of Genes?

„All matter can be reduced to a periodic table of elements, but at a higher level, every living thing can be reduced to a periodic table of genes.“

(Strachan, T., Read, A.P., (2004) Human Molecular Genetics. 3rd ed. Garland Publishing, New Yourk, p. 208)

Page 62: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

James Watson: ”We used to think that our fate was in our stars. Now we know, in large part, that our fate is in our genes.“

Walter Gilbert: „When we have the complete sequence of the human genome, we will know what it is to be a human“

E.O.Wilson:Ethics, as we understand it, is an illusion fobbed on us by our genes to get us to cooperate.

Page 63: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The search for the Holy Grail of who we are, has now reached its culminating phase; the ultimate goal is the acquisition of all the details of our genome... that will transform our capacity to predict what we will become.

Walter Gilbert Le Fanu, J., (2009) Why us? How Science Rediscovered the Mystery of Ourselves. Pantheon Books, New

York.

Page 64: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

E.O. Wilson( On Human Nature)

„The question is no longer whether human social behavior is genetically determined. It is to what extent. The accumulated evidence for a large hereditary component is more detailed and compelling than most persons, including even geneticists, realize. I will go further, it is decisive.“

Page 65: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The psychologist Thomas Bouchard has said, "For almost every behavioral trait so far investigated, from reaction time to religiosity, an important fraction of the variation among people turns out to be associated with genetic variation. This fact need no longer be subject to debate; rather it is time instead to consider its implications.„

http://www.nytimes.com/books/first/a/appleyard-brave.html?_r=2&oref=slogin

Page 66: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Robert Weinberg

So what are you going to do if you begin to find on a chip of a child's DNA that this kid is likely to be very good in language, probably is going to have poor math skills, will be a rather anxious and obsessive person, will have difficulty associating with his or her peers, and is likely to come down with heart disease at the age of 45? How is that going to affect your relationship to that person, that child?

Page 67: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Salvador Luria:“‘Will the Nazi program to eradicate Jewish or otherwise ‘inferior’ genes by mass murder be transformed into a kinder, gentler program to ‘perfect’ human individuals by ‘correcting’ their genomes in conformity perhaps to an ideal ‘white, Judeo-Christian, economically successful’ genotype?“

HGP

Page 68: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Ethical Questions

knowledge gained from the HGP may lead to the construction of a „standard“ human genome. if this occurs, one must ask what variation society

would view as permissible before an individual´s genome was labelled substandart or abnormal?

Page 69: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Ethical Issues

knowledge gained from the HGP may lead to the construction of a „standard“ human genome. if this occurs, one must ask what variation society

would view as permissible before an individual´s genome was labelled substandart or abnormal?

Page 70: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome Diversity ProjectHGDP this project would map DNA from

approximately 25 individuals representing 500 of the world´s 5000 or so different ethnic groups

concerns about discriminations of some ethnics

Page 71: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome Diversity ProjectHGDP first proposed in 1991 by a group of human

geneticist, led by Luca Cavalli-Sforza and Allan Wilson

project was launched in September 1993 the primary goals of the founders were to

advance research into human history and evolution, but they foresaw other possible uses – in medicine, population genetics, anthropology, and other fields

…what they did not foresee was the ethical – and political – storm ahead the Project

(Jobling, M.A., Hurles, M.E., Tyler-Smith, C., (2004) Human Evolutionary Genetics. Garland Publisher, New York, p. 275)

Page 72: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome Diversity ProjectHGDP the HGDP continues to exist but, probably

at least in part because of the political controversy attached to it, has never received substantial funding – and has never come close to achieving its goals

this project would map DNA from approximately 25 individuals representing 500 of the world´s 5000 or so different ethnic groups, a total of 12 500 individuals (25x500)

Page 73: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome Diversity ProjectHGDP RAFI (Rural Advancement Foundation

International) had begun excoriate project as „bio-pirate“ interested in stealing valuable genes from indigenous people underhanded commercial goals planning to undermine indigenous culture overthrow indigenous land rights to help US produce ethnically targeted biological

weapons to clone armies of indigenous warrior slaves

(Jobling, M.A., Hurles, M.E., Tyler-Smith, C., (2004) Human Evolutionary Genetics. Garland Publisher, New York, p. 275)

Page 74: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome Diversity ProjectHGDP Whenever genetics is used to look at nationalities or

ethnicities, its methods, and its history, raise concerns about how the data might be used, or abused, to support racist or nationalistic views. When the groups involved have been oppressed, they may well fear commercial exploitation or worse harms, up to genocide.

And, given history of Australian aboriginal people or Native American Nations, their reluctance to participate is not, and must not be treated as, unreasonable.

Sometimes, in spite of researcher´s best effort, indigenous people will say no. One key to ethical human population genetics research is learning to accept that answer.

(Jobling, M.A., Hurles, M.E., Tyler-Smith, C., (2004) Human Evolutionary Genetics. Garland Publisher, New York, p. 275)

Page 75: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The Ethics of Genome Sequence Publications

as soon as the first sequences were published it became apparent that they could only be used if available in computer readable form

1980s the European Molecular Biology Laboratory

(EMBL) the National Institute of Health (NIH) Japanese National Institute of Genetics

these organizations later joined into an effective international collaboration to share data

Page 76: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The Ethics of Genome Sequence Publications

2003: this community database

(EMBL-bank/GenBank/DDBJ) contains over 40 billion bp of sequence from over 100 000 different organism

All three databases implemented a policy that was both courageous and foresighted: to make all of their data freely available to all (whether they be companies, academics or „John Smith“)

Page 77: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The Ethics of Genome Sequence Publications

By the late 1980s most reputable scientific journals were demanding deposition of sequence data in this database as a pre-condition for the publication of a scientific paper.

This immediately gave rise to a conflict: commercial companies (and some academics) saw their DNA sequence data as a intelectual property that might be turned into money. They were often reluctant to make their data freely available, since this might both compromise patent protection and reduce value of their „property“.

Page 78: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Bermuda Agreement 1996

= all data from the Human Genome Project will be deposited in the public sequence databanks

each sequencing center will release its own data every day

Page 79: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Bermuda Agreement 1996

1998: Celera Genomics „Discovery can´t wait!“

Public consortium had no access to Celera´sequence data

Celera had free access to Public consortium data

Page 80: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome: Invention or Discovery?

Human Genome is a discovery, freely available to all – like calendar or Einstein theory of Relativity or Double Helix of DNA

Human Genome is a invention like a bulb or steam engine

...you can patent invention, but not discovery

Page 81: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome: Discovery

Human Genome is a discovery sequence data of human genome – or any

other organism –are fundamental to biology they are as fundamental as the periodic table

is to chemistry and as Euclid´s axioms are to mathematics

data belong to all of us, they are not commodities to be sold in the

market place like apples and oranges!

Page 82: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human Genome: Discovery

there is also pragmatic reason: databases are most useful if, within a given scientific domain, they are not fragmented

much of modern genomics would simply be impossible if the universe of sequence data were split between hundreds of different databases by allowing publication without sequence data

deposition in the community sequence databse Science has encouraged fragmentation of the universe sequence data

Page 83: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Patenting of Human Genes

genetics research should be a cooperative search for new knowledge, rather the self-interested pursuit of profits

once patenting comes to the fore, researchers may become increasingly reluctant to share information, thereby diminishing its transfer between laboratories

Page 84: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

In the US it costs a woman between $3,000 and $4,000 to be tested for familial breast cancer because a corporation owns the patent for the two genes involved. 

Page 85: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Patenting of Human Genes(Richards, J.E., Hawley, R.S., (2005) The Human Genome. Burlington, Elsevier Academic Press)

the gene can be patented if there is an idea regarding some use that could be made of that gene for a particular purpose, such as screening people to find out if they are at risk for a particular disease

Page 86: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 87: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Ethical Issues: Racism is dead

1,5 milions bp – difference between mother and her daughter

2,25 milions bp - difference between grandmother and granddaughter

3 milions bp - difference between two random chosen people on Earth

Page 88: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Races

Lewotine (1972) used 17 loci (blood groups, serum proteins, red blood cell enzymes) for which variation had been detected by immunological or electrophoretic methods and had allele frequency data available for several populations

the populations were classified into seven „races“ termed Caucasians, Black Africans, Mongoloids, South Asian Aborigines, Amerinds, Oceanins and Australian Aborigines,

based on morphological, linguistic, historical and cultural criteria

Page 89: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Races

the overwhelming conclusion was that most variation lies within population, and that „races“ had no genetic reality,a conclusion reinforced by subsequent analyses using independent population samples and DNA markers

Lewontine concluded: Human racial classification is of no social value and is

positively destructive of social and human relations. Since such racial classifications is now seen to be of virtually no genetic or taxonomic significance either, no justification can be offered for its continuance.

(Jobling, M.A., Hurles, M.E., Tyler-Smith, C., (2004) Human Evolutionary Genetics. Garland Publisher, New York, p. 277)

Page 90: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

„Race“ is not a biological concept

modern population genetics makes the concept of „race“ in the human context biologically meaningless, although socially explosive

polish jews are more similar to polish non-jews than to jews in f.e. Sapin

Page 91: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 92: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

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Page 93: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 94: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 95: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Out of Africa a multiregionální model

Page 96: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Dvě teorie vzniku moderního člověka (multiregionální model a „out of Africa“)

Page 97: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 98: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

"All men are created equal" = moral and political equality

insurance companies: "you should pay according the risk you bring" more risk - you more have to pay but what about genetic predispositions?

Page 99: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

genetic exceptionalism =genetic information is not like other kinds of

informations genetic prophecy - DNA can predict things genetic information affect others gentic information has the history of

stigmatization

Page 100: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

genome is not "a bean bag" ... genome is rather an ecosystem

Page 101: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Chimp Genome and Human genome

What makes us "human"?

Page 102: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 103: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Ethical Issues: The Chimpanzee GenomeAre there any differences between chimps and humans?

The chimpanzee genome is 98.77% identical to the human genome. On average, a typical human protein-coding gene differs from its chimpanzee ortholog by only two amino acid substitutions; nearly one third of human genes have exactly the same protein translation as their chimpanzee orthologs. A major difference between the two genomes is human chromosome 2, which is the product of a fusion between chimpanzee chromosomes 12 and 13.

Page 104: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human and Chimpanzee chromosomes

Page 105: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Human and Chimpanzee chromosomes

chromosomes 12 and 13 in a human ancestor fused end to end to form human chromosome 2

The centromere from ancestral chromosome 12 remained functional on human chromosome 2. while the one from ancestral chromosome 13 did not

Page 106: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Among the 3 billion base pairs in the DNA of both humans and chimpanzees, researchers found differences in 40 million sites.

When measured by changes in their genetic codes, humans and chimpanzees are about 10 times more different than are individual humans from each other.

Page 107: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Evolution at Two Levels in Humans and Chimpanzees

The organismal differences between chimpanzees and humans would ... result chiefly from genetic changes an a few regulatory systems, while amino acid substitutions in general would rarely be a key factor in major adaptive shifts. (Mary-Claire King and Alan Wilson)

That is to say, the allelic substitutions of the genes that encode protein sequences - which seem to be pretty much the same for chimps and humans - are not what is importatnt. The important difference are where, when, and how much the genes are activated

cit. v Gilbert, S.F., Epel, D., (2009) Ecological Developmental Biology. Sinauer Associates, Inc. Sunderland, MA. USA, p. 325

Page 108: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

We cannot see in this why we are so different from chimpanzees. Part of the secret is hidden in there /in the genome/, but we don´t understand it yet.

Svante Paabo Le Fanu, J., (2009) Why us? How Science Rediscovered the Mystery of Ourselves. Pantheon Books, New

York.

Page 109: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Why is there not the slightes hint in the Human Genome of those unique attributes of the upright stance and massively expanded brain that so distinguish us from our primate cousins?

Le Fanu, J., (2009) Why us? How Science Rediscovered the Mystery of Ourselves. Pantheon Books, New York.

Page 110: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Skeleton of the Gorilla and Homo

Roger Fenton (1819-69), 'Skeleton of Man and of the Male Gorilla

(Troglodytes Gorilla)' About 1855Fenton was the official photographer

at the British Museum, which then held collections that are today in the

Natural History Museum. Photographed four years before the publication of Darwin’s On the Origin

of Species, the ape skeleton has been reconstructed in a more upright form

than natural to emphasise the similarities between humans and apes. The gorilla’s left arm shows

evidence of a lion bite.

Page 111: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Auguste RodinWoman Centaur (Mind and Body)

Page 112: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Auguste RodinLa Pensée

Page 113: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

GATTACA

1997

„There is no gene for the human spirit“

… but is it true?

Page 114: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 115: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

How genetically unique are we?

96% with chimpanzee 80% with mouse 50 % with Drosophila 40% with C. elegans 30% with S. cerevisiae

Page 116: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Creationism is dead

51% sequences we share with yeasts 57% sequences we share Brassica

oleracea 98,6% sequences we share wit Pan

troglodytes

Page 117: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Creationism is dead

Collins, F., (2006) The Language of God. Free Press, New York, p. 128)

Page 118: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

"Little People with Wings"

Page 119: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The diverse subtlety of form, shape and colour that distinguishes snowdrop from tulips, flies from frogs and humans, is nowhere to be found.

There is not the slighest hint in the composition of the genes of fly or man to account for why the fly should have six legs, a pair of wings and a brain the size of a full stop, and we should have two arms, two legs and that prodigious brain.

Le Fanu, J., (2009) Why us? How Science Rediscovered the Mystery of Ourselves. Pantheon Books, New York.

Page 120: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

We have moved, in the wake of Genome project, from assuming that we knew the principle, if not the details, of that greatest marvels, the genetic basis of the infinite variety of life, to recognisisng that we not only don´t understand the principles, we have no conception of what they might be.

Le Fanu, J., (2009) Why us? How Science Rediscovered the Mystery of Ourselves. Pantheon Books, New York.

Page 121: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine:

Convention on Human Rights and BiomedicineOVIEDO, 1997

Chapter IV – Human genome Article 11 – Non-discrimination

Any form of discrimination against a person on grounds of his or her genetic heritage is prohibited.

Page 122: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

The Genetic Information Nondiscrimination Act

passed the American Senate in 2003 Act will prevent insurers and employers

from discriminating based on genetic information. This means that an insurance company cannot deny you insurance or charge you more because you have a particular genotype, and that an employer cannot fire you or pay you less because you have a particular genotype.

Page 123: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz
Page 124: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Next Lecture

Do genes influence human behaviour?

...coming soon!

Page 125: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

ENCODE

The Encyclopedia of DNA Elements Project to identify all the functional elements of

the genome and to determine how those work together to turn on or off in particular tissues.

Page 126: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Perhaps you have heard the joke about the guy whose keys fell out of his coat pocket late at night on a darkened street. Realizing later that he was without his keys, he began searching. His companions were surprised to hind him searching vainly injust one place –under the streetlight. Asked why he was limiting his search, he explained, „Anyone knows you can´t find your keys where there´s no light.“

Page 127: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

Sadly, the candidate gene strategy generally suffered the same fate – and we didn´t fid keys.

Why couldn´t this be done more systematically? Why couldn´t we light up the whole street?

Page 128: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz

An additional surprise emerged: for most of the gentic variants that played a role in risk of disease, the problem wasn´t that the glitch led to a garbled protein; rather, the glitch affected whether the responsible gene was turned „off“ or „on“ at the right time and in the right amount.

Collins, F., (2010) The Language of Life. Profile Books LTD. London, GB. p. 138

Page 129: 2013 Marek Vácha The future of customize medicine is in your DNA; don´t wait until you are sick to learn why. Dr. Mehmet Oz