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Bioinformatics

Human Genome Project

GENOME: “The whole hereditary information of an organism that is encoded in the DNA.”
The human genome is the complete set
of genetic information for humans. The human
genome is by far the most complex and largest
genome. Its size spans a length of about 6 feet
of DNA, containing more than 30,000 genes.
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. 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.
 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. 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
Human Chromosome 1 Genetic
polymorphisms (SNPs). One SNP occurs at every ~
Map
1,000 bp of human genome. About 85% of all
differences in human DNAs are due to SNPs.
What is Human Genome Project?
The Human Genome Project (HGP) was an international scientific research project that
aimed to determine the complete sequence of nucleotide base pairs that make up human DNA
and all the genes it contains.

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It is a U.S. govt. project coordinated by the Department of Energy (DOE) and the
National Institutes of Health (NIH). It remains the world's largest collaborative biological
project. The idea was picked up in 1984 by the US government when the planning started, the
project was formally launched in 1990 and was declared complete in 2003. It is a 13 year effort.
The Human Genome Project originally aimed to map the nucleotides contained in a
human haploid reference genome. The "genome" of any given individual is unique; mapping
the "human genome" involved sequencing the genomes of a small number of individuals and
then assembling these together to get a complete sequence for each chromosome. The finished
human genome is thus a mosaic, not representing any one individual.
Participating countries and funding agencies:
In 1990, the 2 major funding agencies, the US Department of Energy (DOE) and
National Institute of Health (NIH), developed an MoU in order to coordinate plans and set the
clock for the initiation of the Project. Most of the government-sponsored sequencing was
performed in 20 universities and research centers in the United States, the United Kingdom,
Japan, France, Germany, Canada, and China. A parallel project was conducted outside the
government sponsorship by the Celera Corporation or the Celera Genomics which was
formally launched in 1998.
The $3-billion project was formally launched in 1990 by the US Department of Energy
and the National Institute of Health. The Human Genome Project was a 13-year-long, publicly
funded project initiated in 1990 with the objective of determining the DNA sequence of the
entire euchromatic human genome within 15 years.
Milestones (History of Human Genome Project)
 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.
 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.
Goals of Human Genome Project:
1. To identify all the genes (approximate 100,000) in human DNA.
2. To determine the sequences of the 3 billion bases that make up human DNA.
3. To develop a genetic linkage map of human genome.
4. To obtain a physical map of human genome.
5. To develop technology for the management of human genome information.
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6. To know the function of genes.

7. Store this information in public databases.
8. Develop tools for data analysis.
9. Transfer related technologies to the private sectors.
10. Address the ethical, legal, and social issues that arise from genome research.
Technical aspects in HGP:
The process of determining the human genome first involves genome mapping, or
characterizing the chromosomes. This is called a genetic map. The next step is DNA
sequencing, or determining the order of DNA bases on a chromosome. These are physical
maps.
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 recognize short
sequences of DNA and cut them at specific sites, therefore, DNA can be cut into many different
fragments. These fragments are the 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 first be amplified, or increased in quantity. Two types of
DNA amplifications are cloning and Polymerase Chain Reactions (PCR).
Now that the DNA has been amplified, sequencing can begin.
Sequencing techniques used in HGP are:-
1) Shotgun sequencing method &
2) Sanger sequencing method
Benefits of Human Genome Project research:
The sequencing of the human genome holds benefits for many fields, from molecular
medicine to human evolution.
 Helps in identifying disease causing gene.
 Identification of mutations linked to different forms of cancer.
 The sequence of the DNA is stored in databases available to anyone on the Internet.
 The U.S. National Center for Biotechnology Information (and sister organizations in
Europe and Japan) house the gene sequence in a database known as GenBank, along
with sequences of known and hypothetical genes and proteins.
 Will allow for advances in agriculture through genetic modification to yield healthier,
more disease-resistant crops.
 Benefitted the advancement of forensic science.

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 Improvements in medicine and Drugs used in genetic or metabolic disorder.

 Microbial genome research for Bio-fuel and environmental cleanup.
 DNA finger printing & forensics.
 Improved agriculture by improving the wild gene of high yielding variety of grain and
livestock.
 Better understanding of species evolution and Human genome.
 More accurate risk assessment by gene mapping.
Whose genome is being sequenced?
A group of researchers have managed to complete a
genetic map of the bacterium Haemophilus influenzae. The
approach called whole Genome Shotgun Sequencing to
sequence the 1,749 genes of the bacterium in minimum time
period. The H. influenzae project was based on an approach
to genomic analysis using sequencing and assembly of
unselected pieces of DNA from the whole chromosome.
ISSUES OF CONCERN:
Ethical, Legal and Social issues of the Human Genome
Project
 Fairness in the use of genetic information.
 Privacy and confidentiality of genetic information.
 Psychological impact, stigmatization, and discrimination.
 Reproductive issues.
 Clinical issues.
 Uncertainties associated with gene tests for susceptibilities and complex conditions.
 Fairness in access to advanced genomic technologies.
 Conceptual and philosophical implications.
 Health and environmental issues.
 Commercialization of products.
 Education, Standards, and Quality control.
 Patent issues.
Future Challenges: What We Still Don’t Know?
1. Gene number, exact locations, and functions.
2. Gene regulation
3. Chromosomal structure and organization
4. Non-coding DNA types, amount, distribution, information content, and functions
5. Coordination of gene expression, protein synthesis, Proteomes and post-translational
events
6. Predicted vs experimentally determined gene function
7. Evolutionary conservation among organisms
8. Disease-susceptibility prediction based on gene sequence variation
9. Genes involved in complex traits and multigene diseases
10. Developmental genetics, genomics.
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