HUMAN GENOME PROJECT

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HUMAN GENOME PROJECT

• Dr. Asli Tolun
• Dept. of Molecular Biology and Genetics
• Bogaziçi University

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DNA helix

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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

• DNA ? codes for proteins
• DNA ATGGCCTTAGATCATAGG
• Coding ATGGCCTTAGATCATAGG
• Protein aa1 aa2 aa3 aa4 aa5 aa6

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GENOMEtotal 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)

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PROTEOMICS

• WHY study it
• Scientific curiosity
• Human evolution
• Interaction of environment with genetics
• Basis for inherited disorders

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The PROJECT

• 1986 proposed
• 1990 initiated
• April 2003 completed (2005)
• April 2004
• Mistakes 1100 000
• Today almost complete

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INTERNATIONAL COLLABORATION

• USA, ENGLAND, FRANCE, GERMANY, JAPAN, CHINA
• 20 research centers

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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

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WHY STUDY GENOMICS?

• Scientific curiosity
• Human evolution
• Interaction of genetics and environment
• Genetic basis of inherited diseases
• Prevention (genetic councelling)
• Developing therapeutic means

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FIRST 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?

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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

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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)

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COMPARATIVE GENOMICS

• Chimpanzee, gorilla, monkeys, mouse, rat, cow,
  dog, chicken, fish, primitive vertebrates, bee,
  mosquito, fruit fly, nematode, yeast, plants,
  bacteria etc.

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UNDERSTANDING GENE FUNCTION

• NUCLEOTIDE SEQUENCE (domains)
• SIMILARITY TO OTHER GENES
• ANIMAL MODELS
• GENETIC DISEASES

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Waardenburg Syndrome
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Leptin gene knock-out mouse
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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 chimps
• MCPH1 gene diverged early

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PRACTICAL 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

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RESEARCH EXAMPLES

• Evolution of stomach ulcer bacterium
• Origin of American dog
• Evolution of crops
• Domestication of animals

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TRANSGENIC ANIMALSRat growth hormone to mouse
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DISEASE GENE HUNT

• BENEFITS
• Scientific
• Families
• Prevention (Genetic counseling)
• Developing therapeutic interventions

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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

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Split Hand/Foot Malformation - AR
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ETHICS

• Universal values
• Honesty / integrity
• Awareness of responsibilities and duties
• Respect for human rights and dignity
• Respect for others rights

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STUDENT ETHICS

• NOT CHEATING in
• Exams
• Homeworks
• Reports
• FOR THESIS WORK
• Obligatory course on bioethics
• Learn research ethics
• Ethical review for research

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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.

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Genetic studies withHUMAN PARTICIPANTS

• Medical applications
• Genetic applications
• Research

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UNESCO 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

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UNESCO 1997 Universal Declaration onthe Human
Genome and Human Rights

• Human genetic data
• Obtaining
• Processing
• Use
• Storage

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UNESCO 2005 Universal Declaration on Bioethics
and Human Rights

• Respect to
• Human dignity
• Human rights
• Basic freedom.

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ETHICAL 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.

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ETHICAL COMMITTEE REVIEWS

• Institutional ethical review boards
• A national ethical council

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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

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PARTICIPANTS RIGHTS

• To know and not to know
• Psychological support
• Access to treatment and cure

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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?

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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.

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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.

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FUTURE SENARIOS

• Obligation for prenatal genetic testing
• Obligatory genetic testing for aggressivity
• Genetic classification in athletes
• Insurance companies demands
• Demands of the employer
• Designers baby.

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KAYNAKÇA

• 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. TÜBA
  Yayinlari http//www.tuba.gov.tr/