1. hgp april 2008

2. THE HUMAN GENOME PROJECT
THE HUMAN GENOME PROJECT published ‘completed’ results 14th April 2003.
WHAT IS IT?
WHAT ARE THE AIMS?
HOW IS IT DONE?
BY WHOM?
WHAT ARE THE BENEFITS?
and, most importantly:
WHAT ARE THE ETHICAL ISSUES WHICH THE HUMAN GENOME PROJECT HAS THROWN UP?
hgp april 2008

3. WHAT IS THE HUMAN GENOME?
The entire genetic makeup of the human cell nucleus.
Genes carry the information for making all of the proteins required by the body for growth and maintenance.
Made up of ~35,000-50,000 genes which code for functional proteins in the body.
Includes non-coding sequences located between genes, which makes up the vast majority of the DNA in the genome (~95%).
hgp april 2008

4. THE GENOME IS WHO WE ARE ON THE INSIDE!
Chromosomes consist of:
DNA - molecular strings of A, C, G, & T base pairs
Genes
DNA sequences that encode proteins
less than 3% of human genome
hgp april 2008

5. THE GENOME IS OUR GENETIC BLUEPRINT
Nearly every human cell contains 23 pairs of chromosomes
and XY or XX
XY = Male
XX = Female
Length of chr 1-22, X, Y together is ~3.2 billion bases (about 2 meters diploid)
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7. HOW DO GENES WORK?
The particular order of nucleotide bases (As, Gs, Cs, and Ts) determines the amino acid composition of proteins.
And it is the proteins in the body which give us almost all our characteristics.
hgp april 2008

8. WHAT IS THE HUMAN GENOME PROJECT?
U.S. govt. project coordinated by the Department of Energy and the National Institutes of Health, launched in 1986.
Aims of the project:
Identify all of the genes in human DNA
Determine the sequence of the 3 billion chemical nucleotide bases that make up human DNA
Store this information in data bases
Develop faster, more efficient sequencing technologies
Develop tools for data analysis
Address the ethical, legal, and social issues (ELSI) that arise from the project.
hgp april 2008

9. TWO DIFFERENT GROUPS COMPETED TO PUBLISH THE HUMAN THE DNA SEQUENCE
The Human Genome Projct is a multinational consortium established by US government research agencies and funded publicly
Celera Genomics is a private company whose former CEO, J. Craig Venter, ran an independent sequencing project
Differences arose regarding who should receive the credit for this scientific milestone
Eventually the two agreed to publish together, though they continued to work apart.
hgp april 2008

10. WHOSE GENOME WAS SEQUENCED?
the first reference genome was a composite genome from several different people.
generated from primary samples taken from numerous anonymous donors across racial and ethnic groups.
hgp april 2008

11. HOW MUCH DATA MAKE UP THE HUMAN GENOME?
Imagine 5000 bases on 1 page…….
CACACTTGCATGTGAGAGCTTCTAATATCTAAATTAATGTTGAATCATTATTCAGAAACAGAGAGCTAACTGTTATCCCATCCTGACTTTATTCTTTATG AGAAAAATACAGTGATTCC
AAGTTACCAAGTTAGTGCTGCTTGCTTTATAAATGAAGTAATATTTTAAAAGTTGTGCATAAGTTAAAATTCAGAAATAAAACTTCATCCTAAAACTCTGTGTGTTGCTTTAAATAATC
AGAGCATCTGC TACTTAATTTTTTGTGTGTGGGTGCACAATAGATGTTTAATGAGATCCTGTCATCTGTCTGCTTTTTTATTGTAAAACAGGAGGGGTTTTAATACTGGAGGAACAA
CTGATGTACCTCTGAAAAGAGA AGAGATTAGTTATTAATTGAATTGAGGGTTGTCTTGTCTTAGTAGCTTTTATTCTCTAGGTACTATTTGATTATGATTGTGAAAATAGAATTTATCC
CTCATTAAATGTAAAATCAACAGGAGAATAGCAAAAACTTATGAGATAGATGAACGTTGTGTGAGTGGCATGGTTTAATTTGTTTGGAAGAAGCACTTGCCCCAGAAGATACACAAT
GAAATTCATGTTATTGAGTAGAGTAGTAATACAGTGTGTTCCCTTGTGAAGTTCATAACCAAGAATTTTAGTAGTGGATAGGTAGGCTGAATAACTGACTTCCTATC ATTTTCAGGTT
CTGCGTTTGATTTTTTTTACATATTAATTTCTTTGATCCACATTAAGCTCAGTTATGTATTTCCATTTTATAAATGAAAAAAAATAGGCACTTGCAAATGTCAGATCACTTGCCTGTGGT
CATTCGGGTAGAGATTTGTGGAGCTAAGTTGGTCTTAATCAAATGTCAAGCTTTTTTTTTTCTTATAAAATATAGGTTTTAATATGAGTTTTAAAATAAAATTAATTAGAAAAAGGCAA
ATTACTCAATATATATAAGGTATTGCATTTGTAATAGGTAGGTATTTCATTTTCTAGTTATGGTGGGATATTATTCAGACTATAATTCCCAATGAAAAAACTTTAAAAAATGCTAGTGA
TTGCACACTTAAAACACCTTTTAAAAAGCATTGAGAGCTTATAAAATTTTAATGAGTGATAAAACCAAATTTGAAGAGAAAAGAAGAACCCAGAGAGGTAAGGATATAACCTTACC
AGTTGCAATTTGCCGATCTCTACAAATATTAATATTTATTTTGACAGTTTCAGGGTGAATGAGAAAGAAACCAAAACCCAAGACTAGCATATGTTGTCTTCTTAAGGAGCCCTCCCCT
AAAAGATTGAGATGACCAAATCTTATACTCTCAGCATAAGGTGAACCAGACAGACCTAAAGCAGTGGTAGCTTGGATCCACTACTTGGGTTTGTGTGTGGCGTGACTCAGGTAATCT
CAAGAATTGAACATTTTTTTAAGGTGGTCCTACTCATACACTGCCCAGGTATTAGGGAGAAGCAAATCTGAATGCTTTATAAAAATACCCTAAAGCTAAATCTTACAATATTCTCAAG
AACACAGTGAA ACAAGGCAAAATAAGTTAAAATCAACAAAAACAACATGAAACATAATTAGACACACAAAGACTTCAAACATTGGAAAATACCAGAGAAAGATAATAAATAT
TTTACTCTTTAAAAATTTAGTTAAAAGCTTAAACTAATTGTAGAGAAAA AACTATGTTAGTATTATATTGTAGATGAAATAAGCAAAACATTTAAAATACAAATGTGATTACTTAAAT
TAAATATAATAGATAATTTACCACCAGATTAGATACCATTGAAGGAATAATTAATATACTGAAATACAGGTCAGTAGAATTTTTTTCAATTCAGCATGGAGATGTAAAAAATGAAAA
TTAATGCAAAAAATAAGGGCACAAAAAGAAATGAGTAATTTTGATCAGAAATGTATTAAAATTAATAAACTGGAAATTTGACATTTAAAAAAAGCATTGTCATCCAAGTAGATGTG
TCTATTAAATAGTTGTTCTCATATCCAGTAATGTAATTATTATTCCCTCTCATGCAGTTCAGATTCTGGGGTAATCTTTAGACATCAGTTTTGTCTTTTATATTATTTATTCTGTTTACTAC
ATTTTATTTTGCTAATGATATTTTTAATTTCTGACATTCTGGAGTATTGCTTGTAAAAGGTATTTTTAAAAATACTTTATGGTTATTTTTGTGATTCCTATTCCTCTATGGACACCAAGGCT
ATTGACATTTTCTTTGGTTTCTTCTGTTACTTCTATTTTCTTAGTGTTTATATCATTTCATAGATAGGATATTCTTTATTTTTTATTTTTATTTAAATATTTGGTGATTCTTGGTTTTCTCAGCC
ATCTATTGTCAAGTGTTCTTATTAAGCATTATTATTAAATAAAGATTATTTCCTCTAATCACATGAGAATCTTTATTTCCCCCAAGTAATTGAAAATTGCAATGCCATGCTGCCATGTGG
TACAGCATGGGTTTGGGCTTGCTTTCTTCTTTTTTTTTTAACTTTTATTTTAGGTTTGGGAGTACCTGTGAAAGTTTGTTATATAGGTAAACTCGTGTCACCAGGGTTTGTTGTACAGATCA
TTTTGTCACCTAGGTACCAAGTACTCAACAATTATTTTTCCTGCTCCTCTGTCTCCTGTCACCCTCCACTCTCAAGTAGACTCCGGTGTCTGCTGTTCCATTCTTTGTGTCCATGTGTTCTC
ATAATTTAGTTCCCCACTTGTAAGTGAGAACATGCAGTATTTTCTAGTATTTGGTTTTTTGTTCCTGTGTTAATTTGCCCAGTATAATAGCCTCCAGCTCCATCCATGTTACTGCAAAGAA
CATGATCTCATTCTTTTTTATAGCTCCATGGTGTCTATATACCACATTTTCTTTATCTAAACTCTTATTGATGAGCATTGAGGTGGATTCTATGTCTTTGCTATTGTGCATATTGCTGCAAG
AACATTTGTGTGCATGTGTCTTTATGGTAGAATGATATATTTTCTTCTGGGTATATATGCAGTAATGCGATTGCTGGTTGGAATGGTAGTTCTGCTTTTATCTCTTTGAGGAATTGCCATG
CTGCTTTCCACAATAGTTGAACTAACTTACACTCCCACTAACAGTGTGTAAGTGTTTCCTTTTCTCCACAACCTGCCAGCATCTGTTATTTTTTGACATTTTAATAGTAGCCATTTTAACT
GGTATGAAATTATATTTCATTGTGGTTTTAATTTGCATTTCTCTAATGATCAGTGATATTGAGTTTGTTTTTTTTCACATGCTTGTTGGCTGCATGTATGTCTTCTTTTAAAAAGTGTCTGTT
CATGTACTTTGCCCACATTTTAATGGGGTTGTTTTTCTCTTGTAAATTTGTTTAAATTCCTTATAGGTGCTGGATTTTAGACATTTGTCAGACGCATAGTTTGCAAATAGTTTCTCCCATTC
TGTAGGTTGTCTGTTTATTTTGTTAATAGTTTCTTTTGCTATGCAGAAGCTCTTAATAAGTTTAATGAGATCCTGATATGTTAGGCTTTGTGTCCCCACCCAAATCTCATCTTGAATTATA
TCTCCATAATCACCACATGGAGAGACCAGGTGGAGGTAATTGAATCTGGGGGTGGTTTCACCCATGCTGTTCTTGTGATAGTGAATGAGTTCTCACGAGATCTAATGGTTTTATGAGG
GGCTCTTCCCAGCTTTGCCTGGTACTTCTCCTTCCTGCCGCTTTGTGAAAAAGGTGCATTGCGTCCCTTTCACCTTCTTCTATAATTGTAAGTTTCCTGAGGCCTTCCCAGCCATGCTGAA
CTTCAAGTCAATTAAACCTTTTTCTTTATAAATTACTCAGTCTCTGGTGGTTCTTTATAGCAGTGTGAAAATGGACTAATGAAGTTCCCATTTATGAATTTTTGCTTTTGTTGCAATTGCTT
TTGACATCTTAGTCATGAAATCCTTGCCTGTTCTAAGTACAGGACGGTATTGCCTAGGTTGTCTTCCAGGGTTTTTCTAATTTTGTGTTTTGCATTTAAGTGTTTAATCCATCTTGAGTTGA
TTTTTGTATATTGTGTAAGGAAGGGGTCCAGTTTCAATCTTTTGCATATGGCTAGTTAGTTATCCCAGTACCATTTATTGAAAAGACAGTCTTTTCCCCATCGCTCGTTTTTGTCAGTTTT
ATTGATGATCAGATAATCATAGCTGTGTGGCTTTATTTCTGGGTTCTTTATTCTGTTCTATTGGTTTATGTCCCTGTTTTTGTGCCAGTACCATGCTGTTTTGGTTAACATAGCCCTGTAGT
ATAGTTTGAGGTCAGATAGCCTGATGCTTCCAGCTTTGTTCTTTTTCTTAAGATTGCCTTGGCTATTTGGCCTCTTTTTTGGTTCCACATGAATTTTAAAACAGTTGTTTCTAGTTTTTGAA
GAATGTCATTGGTAGTTTGATAGAAATAGCATTTAATCTGTAAATTGATTTGTGCAGTATGGCCTTTTAATGATATTGATTCTTCCTATCCATGAGCATGATATGTTTTCCATTTTGTTTG
TATCCTCTCTGATTTCTTTGTGCAGTGTTTTGTAATTCTCAT TGTAGAGATTTTTCACCTCCCTGGTTAGTTGTATTTTACCCTAGATATTT TATTCTTTTTGTGAAAATTGTGAATGGGAT
TGCCTTCCTGATTTGACTGC CAGCTTGGTTACTGTTGGTTTATAGAAATGCTAGTGATTTTTGTACATTG ATTTTCTTTCTAAAACTTTGCTGAAGTTTTTTTTATTAGCAGAAGGAGCT
TTGGGGCTGAGACTATGGGGTTTTCTAGATATAGAATCATGTCAGCTTCAAATAGGGATAATTTTACTTCCTCTCTTCCTATTTGGATGCCCTTTATTTCTTTCTCTTGCCTGATTACTCTG
GCTGGGATTTCCTATGTTGAATAGGAGT CATGAGAGAGGGCATCAAATCTACACATATCAAATACTAACCTTGAATGTCTAGATATTT TATTCTTTTTGTGAAAATTGTGAATGGGAT
hgp april 2008

12. HOW MUCH DATA MAKE UP THE HUMAN GENOME?
3 pallets with 40 boxes per pallet x 5000 pages per box x 5000 bases per page = 3,000,000,000 bases!
To get accurate
sequencing requires
6 time multiplication
Now: Tear up 18 pallets
and reassemble them,
three bases at a time!
hgp april 2008

13. THE BEGINNING OF THE PROJECT
Most the first 10 years of the project were spent improving the technology to sequence and analyze DNA.
Scientists all around the world worked to make detailed maps of our chromosomes and sequence model organisms, like worm, fruit fly, and mouse.
hgp april 2008

14. HOW IS IT ACCOMPLISHED? 3,200,000 piece puzzle anyone?
The DNA sequence is so long that no technology can read it all at once, so it is broken into pieces.
There were millions of clones (small sequence fragments).
The assembly process included finding where the pieces overlapped in order to put the draft together.
3,200,000 piece puzzle anyone?
hgp april 2008

15. What do genes do anyway?
We only have ~27,000 genes, so that means that each gene has to do a lot.
Genes make proteins that make up nearly all we are (muscles, hair, eyes).
Almost everything that happens in our bodies happens because of proteins (walking, digestion, fighting disease). or or
hgp april 2008

16. GENES ARE IMPORTANT
By selecting different pieces of a gene, your body can make many kinds of proteins.
If a gene is “expressed” that means it is turned on and it will make proteins.
hgp april 2008

17. WHAT WE’VE LEARNED FROM OUR GENOME SO FAR…
There are a relatively small number of human genes, less than 30,000, but they have a complex architecture that we are only beginning to understand and appreciate.
We know where 85% of genes are in the sequence
We don’t know where the other 15% are because we haven’t seen them “on”
We only know what about 20% of our genes do so far.
So it is relatively easy to locate genes in the genome, but it is hard to figure out what they do.
hgp april 2008

18. BENEFITS of the HGP
MEDICINE
Improvements in diagnostic and therapeutic applications
Pharmacogenomics – “personal”drugs
Organ replacement
Better understanding of disease susceptibility and gene sensitivity
Protein replacement therapy
Implementation of preventative measures
More gene therapy applications
hgp april 2008

19. BENEFITS of the HGP
Manipulation of embryo development and aging processes
Microbial genome research for fuel and environmental cleanup
DNA forensics
Protection from biological and chemical warfare
Improved agriculture and livestock
Better understanding of human evolution and migration – DNA mutates at a constant rate
More accurate risk assessment
Bioinformatics – the fastest growing natural science
hgp april 2008

20. … but there is a huge MORAL DILEMMA
That which has the potential for good also has the potential for bad. The promise of the Human Genome Project is tempered by the social realities of our modern world. What are some of the moral and ethical issues associated with understanding the Human Genome? Are we as humans prepared to deal with this information? How will you decide your best course of action?
hgp april 2008

21. ETHICAL, LEGAL AND SOCIAL ISSUES (ELSI)
Privacy legislation
Genetic testing (screening)
Patenting - ownership
Forensics
Behavioral Genetics
Genetics in the Courtroom
hgp april 2008

22. OWNERSHIP OF YOUR GENETIC INFORMATION
WHO SHOULD HAVE ACCESS TO YOUR GENETIC INFORMATION?
Employers, Insurers
Schools, Courts
Military, Police
Adoption agencies
WHAT WILL THOSE PEOPLE DO WITH YOUR GENETIC INFORMATION?
hgp april 2008

23. WHO SHOULD OWN AND CONTROL YOUR GENETIC INFORMATION?
hgp april 2008

24. PSYCHOLOGICAL IMPACT AND STIGMATIZATION
Effects on the individual
Effects on society’s perceptions and expectations of the individual
hgp april 2008

25. WHO CAN BE ALLOWED TO MAKE MONEY FROM GENES AND DNA SEQUENCES?
COMMERCIALIZATION
WHO CAN BE ALLOWED TO MAKE MONEY FROM GENES AND DNA SEQUENCES?
The person (or company) who discovered it, or the person whose body it came from?
Should genetic information be the property of humanity?
Is it ethical to charge someone for access to a database of genetic information?
hgp april 2008

26. GENETIC SCREENING
Should testing be done only when there is a family history of genetic disorders?
Should there be screening of whole populations for genetic disorders?
Should testing be done when there is no treatment available?
Who has the right to insist upon genetic testing?
hgp april 2008

27. GENETIC TESTING & REPRODUCTIVE ISSUES
Should genetic screening be undertaken if there are no treatments available for the diseases?
What do you do if genetic testing brings bad news? Who guides you?
Reproductive issues – the use of genetic information in decision-making.
hgp april 2008

28. THIS IS A VERY, VERY COMPLEX ISSUE!
WHAT DO YOU THINK? WHERE DO YOU STAND?
hgp april 2008