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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
FLOW of GENETIC INFORMATION DNA → codes for proteins
DNA: ATGGCCTTAGATCATAGG Coding: ATGGCCTTAGATCATAGG Protein aa1 aa2 aa3 aa4 aa5 aa6
GENOME:total genetic information3.3 billion nucleotides
99.9% are same in all24 chromosomes (24 DNA molecules)Human Genome Project
Total DNA sequence (=> genes)
ProteomicsFunctions 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
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?
Scientific curiosity Human evolution Interaction of genetics and environment Genetic basis of inherited diseases Prevention (genetic councelling) Developing therapeutic means
FIRST RESULTS 2003
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 21% – by all organisms 32% – by all eukaryotes 24% – by all animals 22% – by only vertebrates 1% – only in “humans”
SIMILARITY TO OTHER SPECIESGenes:
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 NUCLEOTIDE SEQUENCE (domains)
SIMILARITY TO OTHER GENES
ANIMAL MODELS
GENETIC DISEASES
Balat Or-Ahayim Hastanesi 14 Mart 2010
Waardenburg Syndrome
Balat Or-Ahayim Hastanesi 14 Mart 2010
Leptin gene knock-out mouse
29 Eylül 2009 Kocaeli Üniversitesi 18
BRAIN 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 chimp’s MCPH1 gene: diverged early
PRACTICAL USE of HGP?
An example60% 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
Balat Or-Ahayim Hastanesi 14 Mart 2010
TRANSGENIC ANIMALSRat growth hormone to mouse
DISEASE GENE HUNT
BENEFITS: 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 7 x
1:1,000 1:4 million 126 x
1:50,000 1:10 billion 6251 x
Split Hand/Foot Malformation - AR
ETHICSUniversal 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
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 withHUMAN PARTICIPANTS Medical applications Genetic applications Research
UNESCO Declarations and Resolutions 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 onthe 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 Apply for all individuals without discrimination
Individual’s advantage should come before that of society and community
Individual’s benefit should be maximized while any potential harm is minimized.
ETHICAL COMMITTEE REVIEWS
Institutional ethical review boards
A national ethical council
OBTAINING 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
PARTICIPANT’S RIGHTS To know and not to know Psychological support Access to treatment and cure
MINORS’ 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?
RESPONSIBILITIES of the STATE National ethics councils
Sufficient ethics training for workers Inform relevant UNESCO committees
about whether the declarations are followed in the country.
CONTROVERCIAL 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.
FUTURE SENARIOS Obligation for prenatal genetic testing Obligatory genetic testing for “aggressivity” Genetic classification in athletes Insurance companies’ demands Demands of the employer ‘Designer’s baby’.
KAYNAKÇAAvrupa Birliği: Avrupa’da Genetik ve Kamu ve Profesyonel Politikalarhttp://europa.eu.int/comm/research/biosociety/pdf/bmh4_ct98_0550_partb.pdfAvrupa 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.htmİngiltere Genetik Test için Danışma Komitesi
ttp://www.doh.gov.uk/genetics/recrev3.htmNürnberg İlkeleri http://ohsr.od.nih.gov/nuremberg.php3UNESCO uluslararası bildirgeler www.unesco.orgİnsan Hakları Taraftarı Tüm Avukat ve Hekimler http://www.glphr.orgABD Başkanlık Biyoetik Kurulu http://www.bioethics.govİngiltere İnsan Genetiği Komisyonu http://hgc.gov.ukGenetik Araştırma ve Uygulamada Etik. TÜBA Yayınları
http://www.tuba.gov.tr/