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HUMAN GENOME PROJECT
Dr. Aslı Tolun
Dept. of Molecular Biology and Genetics
Boğaziçi University
DNA helix
GENETICS
Chemical molecule: a DNA chain
 4 types of nucleotides (A, G, C, T)
 DNA codes for proteins
 Example: insulin gene
→ insulin hormone
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FLOW of GENETIC INFORMATION
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DNA → codes for proteins
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DNA: ATGGCCTTAGATCATAGG
Coding: ATGGCCTTAGATCATAGG
Protein aa1 aa2 aa3 aa4 aa5 aa6
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GENOME:
total genetic information
3.3 billion nucleotides
99.9% are same in all
24 chromosomes (24 DNA molecules)
Human Genome Project
Total DNA sequence (=> genes)
Proteomics
Functions of all genes (proteins)
PROTEOMICS
WHY study it:
 Scientific curiosity
 Human evolution
 Interaction of environment with
genetics
 Basis for inherited disorders
The PROJECT
1986 proposed
1990 initiated
April 2003 ‘completed’ (2005)
April 2004
Mistakes 1:100 000
Today almost complete
INTERNATIONAL COLLABORATION
USA, ENGLAND, FRANCE, GERMANY,
JAPAN, CHINA:
20 research centers
PURPOSE
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All of DNA sequence
Sequences of all genes
Functions of all genes
Establishment of data bases
Develeopment/improvement of techniques
Ethical, legal and social issues
WHY STUDY GENOMICS?
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Scientific curiosity
Human evolution
Interaction of genetics and environment
Genetic basis of inherited diseases
Prevention (genetic councelling)
Developing therapeutic means
FIRST RESULTS 2003
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Genes constitute about 5% of the genome
Genes: < 30 000. (Earlier guess: 80 000)
Half are “unknown genes”
About 99.9% are same in all individuals
A difference of about 3 million nucleotides
-> Susceptibilities to diseases?
MAJORITY OF OUR GENES ARE
SHARED
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21% – by all organisms
32% – by all eukaryotes
24% – by all animals
22% – by only vertebrates
1% – only in “humans”
SIMILARITY TO OTHER SPECIES
Genes:
99% shared by mouse
(diverged 75 million years ago)
61% shared by fruit fly (Drosophila)
43% with a small nematode
(diverged 500 million years ago)
COMPARATIVE GENOMICS
Chimpanzee, gorilla, monkeys,
mouse, rat, cow, dog, chicken,
fish, primitive vertebrates, bee,
mosquito, fruit fly, nematode,
yeast, plants, bacteria etc.
UNDERSTANDING GENE FUNCTION
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NUCLEOTIDE SEQUENCE (domains)
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SIMILARITY TO OTHER GENES
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ANIMAL MODELS
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GENETIC DISEASES
Waardenburg Syndrome
Balat Or-Ahayim Hastanesi
2010
14 Mart
Leptin gene knock-out mouse
Balat Or-Ahayim Hastanesi
2010
14 Mart
BRAIN ENLARGEMENT
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1.23% difference between genes, h vs chimp
Brain/body weight ratio: 3x larger in humans
“Microcephaly genes” identified:
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ASPM gene: very different from chimp’s
MCPH1 gene: diverged early
29 Eylül 2009
Kocaeli Üniversitesi
18
PRACTICAL USE of HGP?
An example
60% of our genes are similar to fruit fly’s
Similarly, 2/3 of our ‘cancer genes’
‘Parkinson gene’ to fruit fly  disease
RESEARCH EXAMPLES
Evolution of stomach ulcer bacterium
Origin of American dog
Evolution of crops
Domestication of animals
TRANSGENIC ANIMALS
Rat growth hormone to mouse
Balat Or-Ahayim Hastanesi
2010
14 Mart
DISEASE GENE HUNT
BENEFITS:
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Scientific
Families
Prevention (Genetic counseling)
Developing therapeutic interventions
FREQUENCY OF DISEASES
RECESSIVES ARE VERY FREQUENT
Carrier
Patient Increase in
freq.
freq.
cousin marriage
1:50
1:10,000
7x
1:1,000 1:4 million
126 x
1:50,000 1:10 billion
6251 x
Split Hand/Foot Malformation - AR
ETHICS
Universal values:
 Honesty / integrity
 Awareness of responsibilities and duties
 Respect for human rights and dignity
 Respect for others’ rights
STUDENT ETHICS
NOT CHEATING in
 Exams
 Homeworks
 Reports
FOR THESIS WORK:
 Obligatory course on bioethics
 Learn research ethics
 Ethical review for research
HGP ETHICAL ISSUES
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No discrimination
Respect to privacy
Confidentiality of data
Informing the subject
Informed consent form
Help to cope with psycological effects
Patents, ownership, etc.
Genetic studies with
HUMAN PARTICIPANTS
Medical applications
 Genetic applications
 Research
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UNESCO Declarations and Resolutions
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1948 Human Rights Universal Declaration
Agreements against discrimination:
1965 Racial discrimination
1979 Discrimination against women
1989 Children’s rights
2001 Genetics and discrimination
1998 Human Genome and Human Rights
Universal Declaration
UNESCO 1997 Universal Declaration on
the Human Genome and Human Rights
Human genetic data:
 Obtaining
 Processing
 Use
 Storage
UNESCO 2005 Universal
Declaration
on Bioethics and Human Rights
Respect to:
 Human dignity
 Human rights
 Basic freedom.
ETHICAL PRINCIPLES
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Apply for all individuals without discrimination
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Individual’s advantage should come before
that of society and community
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Individual’s benefit should be maximized
while any potential harm is minimized.
ETHICAL COMMITTEE REVIEWS
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Institutional ethical review boards
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A national ethical council
OBTAINING CONSENT
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Without pressure, on free will
Those not competent....
Children 11-18 yrs
Sufficiently-informed
A copy of the informed consent form
The right to withdraw consent
Research to be initiated after consent
PARTICIPANT’S RIGHTS
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To know and not to know
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Psychological support
Access to treatment and cure
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MINORS’ RIGHTS
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11-18 yrs: consent
Genetic testing – only if a ‘good reason’
Should the parents know the results?
At what age should the result be told?
By whom?
RESPONSIBILITIES of the STATE
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National ethics councils
Sufficient ethics training for workers
Inform relevant UNESCO committees
about whether the declarations are
followed in the country.
CONTROVERCIAL ISSUES
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Gene therapy
Sex selection in embryo (male/second)
Embryo selection for histocompatibility
Embryo selection for a trait (deafness)
Filing of the genetic data by the state
Availability of that data.
FUTURE SENARIOS
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Obligation for prenatal genetic testing
Obligatory genetic testing for “aggressivity”
Genetic classification in athletes
Insurance companies’ demands
Demands of the employer
‘Designer’s baby’.
KAYNAKÇA
Avrupa Birliği: Avrupa’da Genetik ve Kamu ve Profesyonel Politikalar
http://europa.eu.int/comm/research/biosociety/pdf/bmh4_ct98_0550_partb.pdf
Avrupa Konseyi – Genetik testin etik, yasal ve sosyal açılımları üzerine 25
Öneri ve diğer öneriler http://ec.europa.eu/research/science-society/
ABD Ulusal Sağlık Enstitüleri Sağlık ve İnsan Servisleri Araştırma
Risklerinden Koruma Ofisi
http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm
Helsinki Bildirgesi, Dünya Tıp Birliği http://www.wma.net/e/policy/b3.htm
İngiltere Genetik Test için Danışma Komitesi
ttp://www.doh.gov.uk/genetics/recrev3.htm
Nürnberg İlkeleri http://ohsr.od.nih.gov/nuremberg.php3
UNESCO uluslararası bildirgeler www.unesco.org
İnsan Hakları Taraftarı Tüm Avukat ve Hekimler http://www.glphr.org
ABD Başkanlık Biyoetik Kurulu http://www.bioethics.gov
İngiltere İnsan Genetiği Komisyonu http://hgc.gov.uk
Genetik Araştırma ve Uygulamada Etik. TÜBA Yayınları
http://www.tuba.gov.tr/