THE HUMAN GENOME
PROJECT (HGP) 1990 - 2003
"The human genome underlies
the fundamental unity of all
members of the human family, as
well as the recognition of their
inherent dignity and diversity. In a
symbolic sense, it is the heritage
of humanity.”
Universal Declaration on the Human Genome
and Human Rights
AIMS
PRIMARY ROLE…
•To identify all of the approximate 30,000 genes in human DNA
and determine their locus (position)
…THEN…
•To determine the sequences of the 3 billion chemical base pairs
that make up human DNA, store this information in databases
…AS WELL AS…
•To continue to improve tools for DNA analysis
•To address the ethical, legal, and social issues that may arise
from the project
•To gain an understanding of the function of the non-coding DNA
such as introns within genes and repetitive areas between gene.
Development
•In the 1960’s scientists used cross breeding experiments and linkage studies to map
the relative positions of genes on chromosomes – mostly in drosophila.
•The $6 billion HGP officially started in 1990 with James Watson (as in Watson and
Crick) as director.
•Funding was a joint effort by the governments of several countries including the USA
and UK, as well as from private sources hoping to make financial gains from the
project.
•When Watson resigned from the project in 1992 (due to his dissatisfaction of the
greed displayed by the contributors by trying to patent early identifiable sequences of
the DNA), the Human Genome organisation (HUGO) was established to continue the
project.
•Celera Genomics, a private company, was established and competed with HUGO.
•In 2000 Celera, announced they had sequenced the genome. Many complained they
had an unfair advantage as they could share the results of HUGO, but did not share
their results.
•In 2001 HUGO announced they had sequenced a ‘working draft’ of the genome from
20 different people and found a 99.9% compatibility.
Sequenced Genomes
Why linkage isn’t enough.
•Linkage mapping is adequate when studying where in the
genome a particular gene might be located in comparison
to other genes
•Linkage mapping is NOT adequate in providing the exact
distance between genes. For example we might know that
gene B is between gene A and C, but we don’t know where
gene A, gene B or gene C actually are on a chromosome.
•In order to know where a particular gene is found on a
chromosome we need to under take physical mapping.
•A physical map notes the actual location of a gene on a
chromosome.
Chromosome maps.
http://www.rlc.dcccd.edu/MATHSCI/reynolds/progeria/cellular/chr5678sm.gif
HIGHLIGHTS SO FAR…
•The human genome contains 3 billion nucleotide bases (A, C, T, and G).
•The average gene consists of 3000 bases, but sizes vary greatly, with the
largest known human gene being dystrophin at 2.4 million bases.
•The functions are unknown for more than 50% of discovered genes.
•The human genome sequence is almost (99.9%) exactly the same in all
people.
•About 2% of the genome encodes instructions for the synthesis of proteins.
•Over 40% of the human proteins share similarity with fruit-fly or worm
proteins.
•Genes appear to be concentrated in random areas along the genome, with
vast expanses of non-coding DNA between.
•Chromosome 1 (the largest human chromosome) has the most genes
(2968), and the Y chromosome has the fewest (231).
http://www.mydna.com/genes/genetics/genomics/early_insights.html
Benefits - Evolution
•Study evolution through
germline mutations in various
lineages
•Study migration of different
population groups based on
female genetic inheritance
•Study mutations on the Y
chromosome to trace lineage
and migration of males
•Compare breakpoints in the
evolution of mutations with ages
of populations and historical
events
Benefits - Forensics
•Greater accuracy in identifying the suspect of a
crime by matching their DNA profile with that of
any body tissue found at the scene of the crime.
•Paternity testing (not necessarily a benefit to
every individual) and other family relationships.
•Exoneration of individual falsely accused of a
crime.
•Identify endangered and protected species as an
aid to wildlife officials (could be used for
prosecuting poachers)
•Detect bacteria and other organisms that may
pollute air, water, soil, and food
•Match organ donors with recipients in transplant
programs
•Determine pedigree for seed or livestock breeds
Benefits – Risk assessment
•Assess health damage and risks
caused by radiation exposure,
including low-dose exposures
•Assess health damage and risks
caused by exposure to mutagenic
chemicals and cancer-causing toxins
•Reduce the likelihood of heritable
mutations
Benefits - Microbial
•New energy sources (biofuels)
•Environmental monitoring to detect pollutants
•Protection from biological and chemical warfare
•Safe, efficient toxic waste cleanup
•Understanding disease vulnerabilities and
revealing drug targets
© http://www.biofuels.nrel.gov
•Improved diagnosis of disease
•Earlier detection of genetic predispositions to
disease
•Rational drug design
•Gene therapy and control systems for drugs
•Pharmacogenomics "custom drugs"
?Benefits – Breeding
•Disease, insect, and droughtresistant crops
•Healthier, more productive,
disease-resistant farm animals
•More nutritious produce
•Biopesticides
•Edible vaccines incorporated into
food products
•New environmental cleanup uses
for plants like tobacco
Limitations
•Sequencing the human genome has lead scientists into its
greater complexities. It is far more complicated that they ever
imagined and it is now believed that the human genome and
human function may never be truly understood.
•They now believe that about 98% of the DNA does not code
for proteins. Its function is mostly unknown.
•Even though we might know were a gene sits on a
chromosome, we don’t necessarily know how it functions, or
how its protein functions.
•Learning about the human genome doesn’t teach us to
ethically and sensibly use the information we can gain about
ourselves and others.
STEPING INTO THE FUTURE
Proteomics
•Once scientists have located a particular gene and
sequenced it, they can then study the protein that the gene
makes. The study of proteins is known as proteomics.
•Once the function of the protein has been identified,
scientists can then artificially produce it using transgenic
techniques.
•Transgenics has already been used where the gene for
insulin or Factor lllV has been inserted into cattle.
•“Proteins are central to our understanding of cellular function
and disease processes, and without a concerted effort in
proteomics, the fruits of genomics will go unrealized.” Ian
Humphrey-Smith, HUPO (Human Proteomics Organisation).
STEPING INTO THE FUTURE
Pharmacogenetics
•An ultimate goal of pharmacogenetics is to
understand how someone's genetic make-up
determines how well a medicine works in his or her
body, as well as what side effects are likely to occur.
• In the future, advances gleaned from
pharmacogenetics research will provide information
to guide doctors in getting just enough of the right
medicine to a person - the practice of "personalized
medicine.“
•Pharmacogenetics is already a multi billion dollar
industry.
http://www.mydna.com/genes/pharmaco/library/what_pharmaco.html
STEPING INTO THE FUTURE
Pharmacogenetics
http://www.phpc.cam.ac.uk/epg/IPP.html
•People metabolize drugs at different rates and
tests on genes that are involved in drug
metabolism are being developed to see how
much of a particular drug a person might need.
Why is this so important?
•Studies of people are being under taken who
have certain desired reactions to drugs in order
to perhaps transfer this reaction to others.
•Helps understand who might benefit from
certain drugs.
•Help form a link between genes and the
contribution they make to diseases.
http://www.mydna.com/genes/pharmaco/library/what_pharmaco.html
STEPING INTO THE FUTURE
Environmental Genome Project
•“The mission of the EGP is to improve understanding of human genetic
susceptibility to environmental exposures.”
•This “includes the goal of understanding how individuals differ in their
susceptibility to environmental agents and how these susceptibilities change
over time.”
•Research topics include:
•producing a database of genes that play a role in susceptibility to the
environment
•analysis of genes that respond to the environment by looking at their role
in DNA repair, cell division, metabolism, homeostasis, cell signaling and
cell cycle control
•gaining a better understanding of legal, ethical and social aspects of
environmental health
•molecular epidemiology of environmental disease
STEPING INTO THE FUTURE
Human Genome Diversity Project
•This is a controversial project aimed to map the differences between different racial
and ethnic groups.
•The HGD Project is an effort by anthropologists, geneticists, doctors, linguists, and
other scholars from around the world to document the genetic variation of the human
species worldwide.
•The information will also be used to learn about human biological history, the
biological relationships among different human groups, and may be useful in
understanding the causes of and determining the treatment of particular human
diseases.
•The information this Project gathers may help clarify the history of specific human
populations and of our species as a whole.
•As far as scientists know, no particular genes make a person Irish or Chinese or Zulu
or Navajo. These are cultural labels, not genetic ones. People in those populations
are more likely to have some alleles in common, but no allele will be found in all
members of one population and in no members of any other.
http://www.stanford.edu/group/morrinst/hgdp/faq.html#Q2
STEPING INTO THE FUTURE
Nutrigenomics
•A new science promoting the understanding of a persons diet, their
genetics, health and disease
•It aims to help people to better manage their health by precisely
matching their diets to their genetic makeup
•Studying nutrigenomics will help people manage known genetic and
dietry disorders such as diabeties or lactose intolerance
•Understanding nutrigenomics will help link diet and disease with regard
to diseases such as cancer, heart disease and obesity
Ray Rodriguez manages a new Nutrigenomics centre in the US and
suggests that:
"The research we'll be doing in the Nutrigenomics Center is one of the
first examples of taking the benefits of human genome research from the
lab to the home."
http://nutrigenomics.ucdavis.edu/pressarticles.htm
STEPING INTO THE FUTURE
Ethical and Legal Issues
“We need to create the environment and tools needed by key decision
makers in both the private and public sectors to carefully consider and
respond to the challenges and opportunities that arise from scientific
advances in genetics.”
The Genetics and Public Policy Center The Genetics and Public Policy
Center Web Site
The Council for Responsible Genetics (Council for Responsible Genetics
Web Site) fosters public debate about the social, ethical and environmental
implications of genetic technologies.
The National Workrights Institute - Genetic Discrimination The National
Workrights Institute Web Site The National Workrights Institute is a nonprofit organization based in Princeton, NJ. They believe that all workers
are entitled to their rights in the workplace.
http://www.mydna.com/genes/ethics/discrim/sites/rs_dnapolicy.html
STEPING INTO THE FUTURE
Ethical and Legal Issues –
Some Important Questions
•Who controls the genetic information discovered by the HGP?
•Will rival commercial companies prevent each other and independent
government researchers from developing new tests and therapies by
withholding information and technological advances?
•Will knowledge of our own genetic profiles allow us to avoid disease, or
simply inform us of the inevitable and possibly early death? Many
women who have the breast cancer gene are opting for double
mastectomy even though they may never acquire breast cancer.
•Will we be able to emotionally manage unwanted genetic profiles, or
over react to ‘probabilities’ of possible disease.
•Will our genetic profiles be used against us by employers, insurers and
governments?
References
•Abbott, A. (2001) And now for the Proteome…Nature 409, 747.
•Allan, R. and Greenwood, T. (2001) Year 12 Biology Student Resource and Activity
Manual, Biozone International LTD.
•DOEgenomics (2003) US Department of Energy – Department of Science. Retrieved
from the site http://doegenomes.org/ July 2004.
•Graduate School VLAG Food Technology, Agrobiotechnology, Nutrition and Health
Sciences (2004) Centre for Huma Nutrigenomics http://www.nutrigenomics.nl/ July
2004.
•High Privacy Networks (2004) MyDNA. Retrieved from the site http://www.mydna.com
July 2004.
•Morrison Institute ( 1999) Human Diversity Genome Project. Retrieved from the site
http://www.stanford.edu/group/morrinst/hgdp/faq.html#Q2 July 2004.
•National Institute of Environmental Health Science (2004) Environmental Genome
Project. Retrieved from the site http://www.niehs.nih.gov/envgenom/home.htm July
2004.
References
•NuGO (2004) European Nutrigenomics Organisation. Retrieved from the site
http://www.nugo.org/everyone July 2004.
•Stovall, A., Dean, A. and Chen, H. [no date] Richland College – Cellular Mechanism of
Progeria. Retrieved from site
http://www.rlc.dcccd.edu/MATHSCI/reynolds/progeria/cellular/chr5678sm.gif July 2004.
•University of California (2004) Nutrigenomics. Retrieved from site
http://nutrigenomics.ucdavis.edu/index.htm July 2004.
•Forestry [no date] Frequently asked questions. Retrieved from the site
http://www.forestry.ubc.ca/task39/LT4/faq.html#bottom July 2004.