Human genome project, milestones and ELSI of HGP

1. Human Genome
Project
Dr. N. Yuvaraj
Assistant Professor
Achariya Arts and Science College
Villianur , Puducherry

2. The Human Genome Project (HGP) was an international project led
by the US Dept of Energy, National Institutes of Health &
Welcome Trust (UK) launched in 1990 to map and sequence the
human genome.
The announcement of the draft full DNA sequence on 26 June,
2000 will be a historical day.
Some people said, it will be remembered as the day when we learnt
“what it means to be a human”.

3. The initial proposal for the “Human Genome Project” is considered to
be the 1986 editorial by Renato Dulbecco.
He suggested that the fundamental problems related to cancer can be
addressed by determining the sequence of the entire genome.
Since then efforts have been continued at a global level to study the
entire genome of human and a number of other model organisms.
Already the complete genome of over 20 organisms was sequenced
before scientists achieved the full draft human sequence.
The molecular dissection of the genomes from so many species has
unquestionably changed the scope for scientific and medical research.

4. Salient Features of Human Genome:
 Human genome consists the information of 24 chromosomes (22
autosome + X chromosome + one Y chromosome); in Homo sapiens
2n = 2x = 46
 The human genome contains over 3 billion nucleotide pairs.
 Human genome is estimated to have about 30,000 genes .
 Average gene consists of 3000 bases.

5.  But sizes of genes vary greatly, with the largest known human
gene encoding dystrophin containing 2.5 million base pairs.
 Only about 3% of the genome encodes amino acid sequences
of polypeptides and rest of it junk (repetitive DNA).
 The functions are unknown for over 50% of the discovered
genes.

6.  The repetitive sequences makeup very large portion of human
genome.
 Repetitive sequences have no direct coding function but they
shed light on the chromosome structure, dynamics and
evolution.
 Chromosome 1 has most genes (2968) and Y chromosome has
the lowest (231).
 Almost all nucleotide bases are exactly the same in all people.

7. Genome sequences of different individuals differ for less than
0.2% of base pairs.
Most of these differences occur in the form of single base
differences in the sequence.
These single base differences are called single nucleotide
polymorphisms (SNPs).
One SNP occurs at every ~ 1,000 bp of human genome.
About 85% of all differences in human DNAs are due to SNPs.

8. Milestones of HGP
1986 The birth of the Human Genome Project.
1990 Project initiated as joint effort of US Department of
Energy and the National Institute of Health.
1994 Genetic Privacy Act: to regulate collection, analysis,
storage and use of DNA samples and genetic information
is proposed.
1996 Welcome Trust joins the project.

9. 1998 Celera Genomics (a private company founded by Craig
Venter) formed to sequence much of the human genome
in 3 years.
1999 Completion of the sequence of Chromosome 22-the first
human chromosome to be sequenced.
2000 Completion of the working draft of the entire human
genome.
2001 Analysis of the working draft are published.
2003 HGP sequencing is completed and Project is declared
finished two years ahead of schedule.

10. 1. To identify all the genes in human DNA.
2. To develop a genetic linkage map of human genome.
3. To obtain a physical map of human genome.
4. To develop technology for the management of human genome
information.
Goals of human genome project

11. 5. To know the function of genes.
6. Determine the sequences of the 3 billion chemical base pairs
that make up human DNA.
7. Store this information in public databases.
8. Develop tools for data analysis.
9. Transfer related technologies to the private sectors.

12. Shotgun DNA sequencing
Shotgun sequencing is an approach used to decode an
organism's genome by shredding it into smaller fragments
of DNA which can be sequenced individually.
The sequences of these fragments are then ordered, based
on overlaps in the genetic code, and finally reassembled
into the complete sequence.

13. The output from an automated DNA sequencing robot
Each peak shows the presence of a particular base. The
sequence of bases in a given stretch of DNA can therefore be
read from the order of the peaks along the trace.
The
Sanger
Institute,
Wellcome
Images

14. From the very beginning, the Genome Project has been in the
limelight for various reasons including the potential benefits such
as:
1. Medical Prospects
2. Scientific Prospects
3. Agricultural Prospects
4. Environmental Applications
5. Use in Forensic Science
6. Economic Implications

15. Medical Prospects
The central thrust to the Human Genome Project was undoubtedly for
biomedical research.
Already the genes for many diseases including for example, various
cancers, Alzheimer’s disease, and polycystic kidney disease, have been
identified.
Genomic sequencing allows rapid and accurate diagnosis for individuals.
Initially the sequencing of human genome has led to a shift towards
preventive medicine rather than curative, because further research is
needed to develop therapies.

16. Earlier detection of genetic predispositions to disease can be
used for late onset of genetically inherited diseases.
Such discoveries will enable us to work out which combinations of
genes and environmental factors will lead to disease.
In addition gene therapy is being tested.
Other advantages of the sequencing include genetic testing and
screening, and its use in reproductive technologies for
preimplantation diagnosis.

17. Knowing the genes helps in understanding the molecular basis of
medicine.
So that drugs can be designed to target the cause of the
disease.
The drugs can be designed for specific individuals,
pharmacogenics, “custom drugs”, which will change the prescription
of drugs.
Also in the assessment of health damage and risks caused by
exposure to mutagenic chemicals and cancer causing toxins, to
reduce the likelihood of heritable mutations.

18. Scientific Prospects
One of the ideals of science is freedom for self-understanding.
The sequencing of the genome will provide new clues on how we
evolved.
It would help us to understand what it means to be a human from
different historical perspectives of bioarchealogy, anthropology,
evolution, and human migration.
Broader questions on the evolution of Homo Sapiens, the extent of
human diversity, how much we share with nature or what makes us
different from others will be answered by comparisons of genomes.

19. Environmental Applications
Taking into account the potential advantages of the HGP, similar
public and private-funded projects were started to sequence the
genomes of various microbes.
Besides their role in disease, a further reason is that microbes
play a critical role in biogeochemical cycles.
Annotation and analysis of microbial genomes will help in
identifying and harnessing their capabilities to address the
environmental problems, their use in energy production that can
be used as biofuels, as an answer to the limited natural resources
available.

20. Use in Forensic Science
Forensic science is one of the fields that is also expected to be
benefited from the genome sequencing, especially in the
identification of criminals and victims of some tragedy.
The genome project is expected to provide clues to examine the
context and the environment in which the science and the law meet.
The other examples of DNA uses for forensic identification include,
identifying endangered and protected species, help in establishing
relationships with family members.

21. Economic Implications
The Human Genome Project is the largest single biological
project ever undertaken.
For example, just the government budget in the United States
started with US $28 million in 1988, and was at US $361 million
in 2000, approximately a twelve-fold increase in the funding.
Other governments also spent much, and private investment at
least was equal to this.

22. Such a huge monetary investment in itself testifies to the
foreseen benefits out of the sequencing.
Nevertheless the cost-effectiveness of the project was under
criticism especially in early years.
The critiques are apprehensive about existing gaps in the genome.
The questions of patenting of DNA, and genes by governments and
private companies, intellectual property rights and benefit-sharing,
have been particularly debated, and can be seen in the public
announcements of first draft human genome sequence in year 2000.

23. ETHICAL LEGAL AND SOCIAL ISSUES OF HGP

24. Ethical Concerns of human genome project such as
1. Beneficence,
2. Do no harm,
3. Human rights,
4. Animal rights,
5. Authority,
6. Autonomy,
7. Ownership,
8. Justice,
9. Confidentiality and privacy,
10. Responsibility,
11. Scientists and social duty, and
12. Consequences,
that will effect all parameters of life on this planet.

25. Since the beginning of the Human Genome Project, many ethical
questions were raised.
Recognizing that, DOE and the NIH allocated 3–5% of their total
expenditure on HGP for the ELSI arising out of the Genome Project.
This represented the world’s largest bioethics program.
The European Commission only started funding the HGP when it
had set up an ELSI program.
Since then there have been contemporary efforts going on to
answer some of the bioethical challenges of the Human Genome
Project.

26. Different sectors of society have been involved in the HGP
1. Ordinary people,
2. patients,
3. scientists,
4. industry,
5. governments,
6. legal system,
7. regional and international organizations, and
8. United Nations.

27. (a) Beneficence
The principle of beneficence signifies an obligation to benefit
others or to seek their good and it has been the foundation of many
codes.
The motive of the HGP is also based on the principle of beneficence
to all, be it medical patients, health professionals, public institutions
or private companies.
Beneficence is the impetus for further research into ways of
improving health and agriculture, and for protecting the environment.
Beneficence supports the concept of experimentation, if it is
performed to lead to possible benefits.

28. (b) Do no harm
It is the basis for the principles of justice and confidentiality and
philanthropy.
Two main ethical arguments in the Human Genome Project revolve
around the moral concept of justice and confidentiality that are
discussed separately.
(c) Human rights
In simple terms, the human body can not be used as an experimental
“organism” without consent.
This is enshrined in codes governing medical experimentation, such as
the Nuremberg Code and the Helsinki Declaration.

29. (d) Animal rights
Ethical guidelines for research on non-human animals are based
on the assertion that
Animals are sentient, have conscious experiences, and feel pain
and suffering, especially the vertebrate animals.
Usually the benefits of discoveries to humans generally
overweigh
the suffering of animals.
Animals cannot be regarded as means of achieving our goals.

30. (e) Authority
Many people raised doubts about who should be involved in the
sequencing of the genome and who should do the work.
The project required a multi-disciplinary approach involving medical
experts, biologists, bioethicists, information specialists, computer
experts and many others for data banking and analysis.
The multidisciplinary authorization of the Genome Project has on
one hand rewarded it with speeding the process, on the other hand
it aroused conflict between different groups because of the
inherent interests of their respective
fields.

31. (f) Autonomy
The concept of autonomy in bioethics gives each individual the
recognition of the human capacity for self-determinism and
being different in spite of sharing same DNA which is regarded
as a “common heritage”.
(g) Ownership
The competition for the genome sequencing between the
publically funded Genome Project and the world’s leading
private company Celera Genomics is well known.
The fear behind this is the unwarranted risk of data
ownership.

32. (h) Justice
The other side of the possibility for transforming medicine is who
will actually benefit?
Will everyone have access to such revolutionized health care?
There is a fear that it might widen the gap between rich and
poor.
In the developing world, the Human Genome sequencing may not
be the first choice for better treatment, where millions of people
do not even have access to basic medical treatment.

33. (i) Confidentiality and privacy
It will not be surprising if in the next few years we all will be
able to get our individual genomes sequenced.
The privacy of the genetic information is reinforced not only
because of the presumed prospects for the use of such
information beyond medical reasons, for instance, discrimination
of the “genetic underclass” at different levels,

34. (j) Responsibility
The responsibility of use or the misuse of the genetic information
is an individual decision, but what is useful for one may not be
useful for others.
The definition of “misuse” is also debatable.
(k) Scientists and social duty
The scientific community has to bear the moral responsibility for
using very powerful knowledge, as agreed in the UNESCO
Declaration on the Human Genome and Human Rights.
But there always lies the danger of misusing scientific freedom.

35. (l) Consequences
The consequences of the HGP are affirmative only when used in a
proper way, for the well being of all of humanity.
The tremendous potential of the technology is unquestionable.
We have to use the precautionary principle approach, which says we
need to be very careful to avoid harm.
Human Genome Organisation (HUGO) has proposed guidelines to
address some of the ethical and legal requirements related to HGDP.
The HGDP makes us consider our roots and their importance (or not)
in modern society.