THE HUMAN

GENOME PROJECT
BY - SACHI PASAD
 INDEX
• Introduction to HGP

• Objectives

• Participating countries and funding agencies

• Pioneers of the HGP

• Mapping strategies

• Sequencing strategies

• Shotgun method

• Sanger method

• Timeline

• Applications
WHAT IS THE HUMAN GENOME PROJECT?

The Human Genome Project is an research effort aimed at deciphering the chemical makeup of the entire human
genetic code (i.e., the genome).

HGP was initiated in 1990 under the leadership of American geneticist Francis Collins, with support from the
US. Department of Energy and the National Institutes of Health (NIH)

In 1998 a private-sector enterprise, Celera Genomics, headed by American biochemist and former NIH
scientist J. Craig Venter, began to compete with and potentially undermine the publicly funded HGP.

Although the legal and financial reasons remain unclear, the rivalry between Celera and the NIH ended when
they joined forces, thus speeding completion of the rough draft sequence of the human genome.

In April 2003, coinciding with the 50th anniversary of the publication that described the double-helical structure
of DNA, written by British biophysicist Francis Crick and American geneticist and biophysicist James D.
Watson, the HGP was declared complete.
 MAIN OBJECTIVES OF HIP

• To Sequence the Entire Human Genome:

• To Identify and Map All Genes in the Human Genome:
• To Determine the Sequence of Chemical Base Pairs:
• To Develop New Technologies and Methods:
• To Store and Organize Genomic Information:
• To Explore Genetic Variation:
• To Promote International Collaboration:
• To Advance Biomedical Research and Medicine:
PARTICIPATING COUNTRIES
AND FUNDING AGENCIES

The Human Genome Project could not have

been completed as quickly and effectively
without the dedicated participation of an
international consortium of thousands of
researchers.

The sequencing of the human genome involved

researchers from 20 separate universities and
research centers across the United States, United
Kingdom, France, Germany, Japan and China.
The groups in these countries became known as
the International Human Genome Sequencing
Consortium.

Shown (from left to right) are: David

Bentley, John Sulston, and Eric Green in
the front row and Richard McCombie,
Richard Gibbs, Richard Wilson, and
Elson Chen in the back row.
PIONEERS OF THE HGP

1.Francis Collins: As a key figure in the Human Genome Project, Francis Collins led the international effort to
map and sequence the human genome, revolutionizing our understanding of genetics and paving the way for
advancements in personalized medicine.
2.Robert Shinsheimer: Shinsheimer played a crucial role in conceptualizing the Human Genome Project,
advocating for the systematic mapping and sequencing of the human genome, which laid the foundation for
modern genomics research.
3.Charles Delisi and David smith: Delisi and Smith contributed to the computational aspects of the Human
Genome Project, developing algorithms and bioinformatics tools that facilitated the analysis and interpretation
of the vast amounts of genetic data generated, accelerating the project's progress.
4.James Watson: While not directly involved in the Human Genome Project, James Watson's earlier discovery of
the structure of DNA alongside Francis Crick provided the fundamental framework upon which the project was
built, inspiring and guiding subsequent research in genetics and molecular biology.
5.Jim kent: Kent developed critical bioinformatics tools and techniques, including the UCSC Genome Browser,
which enabled researchers to visualize and analyze the human genome sequence data generated by the Human
Genome Project, greatly facilitating its accessibility and utility for the scientific community.
Photo from the 1989 Banbury meeting
MAPPING STRATEGIES

• Genetic markers are invaluable for genome mapping

• Markers are any inherited physical or molecular
characteristics that are different among individuals of a
population (polymorphic)
• A genetic map shows the relative locations of these specific
markers on the chromosomes
• An example of a marker includes restriction fragment length
polymorphisms (RFLP)
• Used in RFLP markers are restriction enzymes. These
enzymes recongnize short sequences of DNA and cut them at
specific sites, therefore, DNA pieces used in physical maps
• RFLPs reflect sequence differences in DNA sites which are
cleaved by restriction enzymes.
SEQUENCING
STRATEGIES
• To sequence DNA it must be amplified, or
increased in quantity
• Two types of DNA amplifications are
cloning and Polymerase chain reaction
(PCR)
• Now that the DNA has been amplified,
sequencing can begin
• Sequencing techniques used in HGP are:-

1.Shotgun Sequencing
2.Sanger method

HUMAN GENOME PROJECT

SANGER METHOD

The Sanger method, also known as the chain termination

method, is a technique used for DNA sequencing. It was
developed by Frederick Sanger and his colleagues in the late
1970s and revolutionized the field of genetics by allowing
scientists to determine the precise order of nucleotides in a
DNA molecule.
PROCEDURE
1. DNA Fragmentation: The DNA to be sequenced is first fragmented into smaller pieces, typically using restriction enzymes or
PCR (Polymerase Chain Reaction).

2. Primer Annealing: A short single-stranded DNA primer, complementary to a specific region of the DNA template, is annealed
(paired) to the DNA fragment. This primer serves as the starting point for DNA synthesis.

3. DNA Synthesis: DNA polymerase, along with the four nucleotide bases (A, T, C, G) and small amounts of special nucleotides
called dideoxynucleotides (ddNTPs), is added to the reaction mixture. These ddNTPs lack a hydroxyl group at the 3' carbon,
preventing further DNA chain elongation when they are incorporated into the growing DNA strand.

4. Chain Termination: During DNA synthesis, when a ddNTP is randomly incorporated into the growing DNA strand instead of a
regular nucleotide, it terminates the chain because it lacks the 3' hydroxyl group required for the formation of the phosphodiester
bond with the next nucleotide. Each ddNTP is labeled with a different fluorescent dye corresponding to one of the four bases.

5. Gel Electrophoresis: The terminated DNA fragments of varying lengths are separated by size using gel electrophoresis. The gel is
exposed to an electric field, causing the DNA fragments to migrate through the gel matrix based on their size, with shorter
fragments traveling faster than longer ones.

6. Visualization: The separated DNA fragments are visualized under UV light, and the fluorescence emitted by the labeled ddNTPs
allows for the determination of the DNA sequence. By analyzing the order in which the fluorescent signals appear, the sequence
of nucleotides in the original DNA fragment can be deduced.
APPLICATIONS
OF HGP
• The detailed genetic, physical, and sequence maps developed by the Human Genome Project also will be
critical to understanding the biological basis of complex disorders resulting from the interplay of multiple
genetic and environmental influences, such as diabetes; heart disease; cancer; and psychiatric illnesses,
including alcoholism.

• Molecular Medicine - During the past 3 years, positional cloning has led to the isolation of more than 30
disease-associated genes. The location of BRCA1 first was narrowed to a DNA fragment of several hundred
thousand nucleotides containing many genes.
• Diagnostics - Although DNA testing offers a powerful new tool for identifying and managing disease, it
also poses several medical and technical challenges. The number and type of mutations for a particular
disease may be few, as in the case of achondroplasia, 5 or many, as in the case of cystic fibrosis and
hereditary breast cancer
• Therapeutics - These treatment approaches range from the mass production of natural substances (e.g.,
blood-clotting factors, growth factors and hormones, and interleukins and interferons 6) that are effective in
treating certain diseases to gene-therapy strategies.
BIBLIOGRAPHY
Collins, Francis S. “The Human Genome Project.” PubMed Central (PMC), 1995.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875757/#:~:text=The%20Human%20Genome%20Project%20is,both%20rare
%20and%20common%20diseases.

“Complex Diseases: Research and Applications | Learn Science at Scitable,” n.d. https://www.nature.com/scitable/topicpage/complex-
diseases-research-and-applications-748/#.

Alfano, Andrea. “Who (Else) Was at Banbury in 1989 Setting the Stage for the Human Genome Project? | Cold Spring Harbor Laboratory.”
Cold Spring Harbor Laboratory, June 13, 2019. https://www.cshl.edu/labdish/who-else-was-at-banbury-in-1989-setting-the-stage-for-
the-human-genome-project/.

Craine, Anthony G. “Francis Collins | Biography, NIH, Religion, Human Genome Project, & Facts.” Encyclopedia Britannica, January 3,
2024. https://www.britannica.com/biography/Francis-Collins.

Genome.gov. “Human Genome Project Fact Sheet,” n.d. https://www.genome.gov/about-genomics/educational-resources/fact-sheets/human-

genome-project#:~:text=The%20sequencing%20of%20the%20human,International%20Human%20Genome%20Sequencing
%20Consortium.

Fridovich-Keil, Judith L. “Human Genome Project (HGP) | History, Timeline, & Facts.” Encyclopedia Britannica, January 9, 2024.
https://www.britannica.com/event/Human-Genome-Project.