Title: HUMAN GENOME PROJECT
1HUMAN GENOME PROJECT
- Dr. Asli Tolun
- Dept. of Molecular Biology and Genetics
- Bogaziçi University
2 DNA helix
3GENETICS
- Chemical molecule a DNA chain
- 4 types of nucleotides (A, G, C, T)
- DNA codes for proteins
- Example insulin gene
- ? insulin hormone
4FLOW of GENETIC INFORMATION
- DNA ? codes for proteins
- DNA ATGGCCTTAGATCATAGG
- Coding ATGGCCTTAGATCATAGG
- Protein aa1 aa2 aa3 aa4 aa5 aa6
5GENOMEtotal genetic information
- 3.3 billion nucleotides
- 99.9 are same in all
- 24 chromosomes (24 DNA molecules)
- Human Genome Project
- Total DNA sequence (gt genes)
- Proteomics
- Functions of all genes (proteins)
6PROTEOMICS
- WHY study it
- Scientific curiosity
- Human evolution
- Interaction of environment with genetics
- Basis for inherited disorders
-
7The PROJECT
- 1986 proposed
- 1990 initiated
- April 2003 completed (2005)
- April 2004
- Mistakes 1100 000
- Today almost complete
8INTERNATIONAL COLLABORATION
- USA, ENGLAND, FRANCE, GERMANY, JAPAN, CHINA
- 20 research centers
9PURPOSE
- 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
10WHY STUDY GENOMICS?
- Scientific curiosity
- Human evolution
- Interaction of genetics and environment
- Genetic basis of inherited diseases
- Prevention (genetic councelling)
- Developing therapeutic means
11FIRST RESULTS 2003
- Genes constitute about 5 of the genome
- Genes lt 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
- -gt Susceptibilities to diseases?
12MAJORITY OF OUR GENES ARE SHARED
- 21 by all organisms
- 32 by all eukaryotes
- 24 by all animals
- 22 by only vertebrates
- 1 only in humans
13SIMILARITY 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)
14COMPARATIVE GENOMICS
- Chimpanzee, gorilla, monkeys, mouse, rat, cow,
dog, chicken, fish, primitive vertebrates, bee,
mosquito, fruit fly, nematode, yeast, plants,
bacteria etc.
15UNDERSTANDING GENE FUNCTION
- NUCLEOTIDE SEQUENCE (domains)
- SIMILARITY TO OTHER GENES
- ANIMAL MODELS
- GENETIC DISEASES
16Waardenburg Syndrome
17Leptin gene knock-out mouse
18BRAIN ENLARGEMENT
- 1.23 difference between genes, h vs chimp
- Brain/body weight ratio 3x larger in humans
- Microcephaly genes identified
- ASPM gene very different from chimps
- MCPH1 gene diverged early
19PRACTICAL USE of HGP?
- An example
- 60 of our genes are similar to fruit flys
- Similarly, 2/3 of our cancer genes
- Parkinson gene to fruit fly ? disease
20RESEARCH EXAMPLES
- Evolution of stomach ulcer bacterium
- Origin of American dog
- Evolution of crops
- Domestication of animals
21TRANSGENIC ANIMALSRat growth hormone to mouse
22DISEASE GENE HUNT
- BENEFITS
- Scientific
- Families
- Prevention (Genetic counseling)
- Developing therapeutic interventions
23 FREQUENCY OF DISEASES
- RECESSIVES ARE VERY FREQUENT
- Carrier Patient Increase in
- freq. freq. cousin marriage
- 150 110,000 7 x
- 11,000 14 million 126 x
- 150,000 110 billion 6251 x
24(No Transcript)
25Split Hand/Foot Malformation - AR
26(No Transcript)
27(No Transcript)
28ETHICS
- Universal values
- Honesty / integrity
- Awareness of responsibilities and duties
- Respect for human rights and dignity
- Respect for others rights
29STUDENT ETHICS
- NOT CHEATING in
- Exams
- Homeworks
- Reports
- FOR THESIS WORK
- Obligatory course on bioethics
- Learn research ethics
- Ethical review for research
-
30HGP ETHICAL ISSUES
- No discrimination
- Respect to privacy
- Confidentiality of data
- Informing the subject
- Informed consent form
- Help to cope with psycological effects
- Patents, ownership, etc.
31Genetic studies withHUMAN PARTICIPANTS
- Medical applications
- Genetic applications
- Research
-
32UNESCO Declarations and Resolutions
- 1948 Human Rights Universal Declaration
- Agreements against discrimination
- 1965 Racial discrimination
- 1979 Discrimination against women
- 1989 Childrens rights
- 2001 Genetics and discrimination
- 1998 Human Genome and Human Rights Universal
Declaration
33UNESCO 1997 Universal Declaration onthe Human
Genome and Human Rights
- Human genetic data
- Obtaining
- Processing
- Use
- Storage
-
34UNESCO 2005 Universal Declaration on Bioethics
and Human Rights
- Respect to
- Human dignity
- Human rights
- Basic freedom.
-
35ETHICAL PRINCIPLES
- Apply for all individuals without discrimination
- Individuals advantage should come before that of
society and community - Individuals benefit should be maximized while
any potential harm is minimized.
36ETHICAL COMMITTEE REVIEWS
- Institutional ethical review boards
- A national ethical council
37OBTAINING CONSENT
- 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
38PARTICIPANTS RIGHTS
- To know and not to know
- Psychological support
- Access to treatment and cure
39MINORS RIGHTS
- 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?
40RESPONSIBILITIES of the STATE
- National ethics councils
- Sufficient ethics training for workers
- Inform relevant UNESCO committees about whether
the declarations are followed in the country.
41CONTROVERCIAL ISSUES
- 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.
42FUTURE SENARIOS
- Obligation for prenatal genetic testing
- Obligatory genetic testing for aggressivity
- Genetic classification in athletes
- Insurance companies demands
- Demands of the employer
- Designers baby.
43KAYNAKÇA
- Avrupa Birligi Avrupada 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 açilimlari üzerine 25 Öneri ve diger
öneriler http//ec.europa.eu/research/science-soci
ety/ - ABD Ulusal Saglik Enstitüleri Saglik ve Insan
Servisleri Arastirma Risklerinden Koruma Ofisi
http//ohrp.osophs.dhhs.gov/humansubjects/guidance
/45cfr46.htm - Helsinki Bildirgesi, Dünya Tip Birligi
http//www.wma.net/e/policy/b3.htm - Ingiltere Genetik Test için Danisma Komitesi
ttp//www.doh.gov.uk/genetics/recrev3.htm - Nürnberg Ilkeleri http//ohsr.od.nih.gov/nuremberg
.php3 - UNESCO uluslararasi bildirgeler www.unesco.org
- Insan Haklari Taraftari Tüm Avukat ve Hekimler
http//www.glphr.org - ABD Baskanlik Biyoetik Kurulu http//www.bioethics
.gov - Ingiltere Insan Genetigi Komisyonu
http//hgc.gov.uk - Genetik Arastirma ve Uygulamada Etik. TÃœBA
Yayinlari http//www.tuba.gov.tr/