BIOLOGY PROJECT

Kamala Niketan
Montessori
school

HUMAN GENOME
PROJECT (HGP)
M.NAVEEN DOSS
XII - D

ACKNOWLEDGEMENT
I would like to express my special thanks of gratitude to my
Biology teacher Mrs. Praveena as well as our principal Mrs.
Mala Sivakumar who gave me the golden opportunity to do
this wonderful report on the topic Human Genome Project
(HGP), which also helped me in doing a lot of Research and
I came to know about so many new things.
Secondly I would also like to thank my parents and friends
who helped me a lot in finishing this project within the limited
time.
I am making this project not only for marks but to also
increase my knowledge.
I ONCE AGAIN THANK EVERYBODY WHO HAS
HELPED ME IN ACCOMPLISHING MY JOB

CONTENTS

Introduction

Why Study Our Genome?

Human Genome Project

Ethical, Legal and Social Issues

Observation

Conclusion

INTRODUCTION
Although every person on our planet is built from the same
blueprint, no two people are exactly the same. While we are
similar enough to readily distinguish ourselves from other living
creatures we also celebrate our individual uniqueness. So what is
it that makes us all human, yet unique? Our DNA.

THE STUFF THAT MAKES US WHO WE ARE

Our DNA (Deoxyribo Nucleic Acid) is found in the nucleus of
every cell in our body (apart from red blood cells, which dont
have a nucleus). DNA is a long molecule, made up of lots of
smaller units. To make a DNA molecule you need:

nitrogenous basesthere are four of these: adenine (A),

thymine (T), cytosine (C), guanine (C)
carbon sugar molecules
phosphate molecules

If you take one of the four nitrogenous bases, and put it together
with a sugar molecule and a phosphate molecule, you get a
nucleotide base. The sugar and phosphate molecules connect the
nucleotide bases together to form a single strand of DNA.
Two of these strands then wind around each other, making the
twisted ladder shape of the DNA double helix. The nucleotide
bases pair up to make rungs of the ladder, and the sugar and
phosphate molecules make the sides. The bases pair up together
in specific combinations: A always pairs with T, and C always
pairs with G to make base pairs.

Put three billion of these base pairs together in the right order,
and you have a complete set of human DNAthe human
genome. This amounts to a DNA molecule about a metre long.
Its the order in which the base pairs are arrangedtheir
sequencein our DNA that provides the blueprint for all living

things and makes us what we are. The DNA sequence of the

base pairs in a fishs DNA is different to those in a monkey.
The base pair sequence of all people is nearly identicalthats
what makes us all humans. However, there are small differences
in the order of the three billion base pairs in everyones DNA that
cause the variations we see in hair colour, eye colour, nose shape
etc. No two people have exactly the same DNA sequence (except
for identical twins, because they came from a single egg that split
into two, forming two copies of the same DNA).

Identical Twins

Population with wide range of

characters

We get our DNA from our parents. The DNA of the human
genome is broken up into 23 pairs of chromosomes (46 in total).
We receive 23 from our mother and 23 from our father. Egg and
sperm cells have only one copy of each chromosome so that
when they come together to form a baby, the baby has the normal
2 copies. Three billion is a lot of base pairs, and together they
contain an enormous amount of information.

WHY STUDY OUR GENOME?

Working out the sequence of the base pairs in all our genes
enables us to understand the code that makes us who we are.
This knowledge can then give us clues on how we develop as
embryos, why humans have more brainpower than other animals
and plants, and what happens in the body to cause cancer. But
establishing the sequence of three billion base pairs is a BIG task.
The great and ambitious research program that sought to do this
was called the Human Genome Project.

Francis Collins, former director of the National

Human Genome Research Institute, led the
Human Genome Project.

The idea of the Human Genome Project was born in the 1970s,
when scientists learned how to clone small bits of DNA, around
the size of a gene. To clone DNA, scientists cut out a fragment of
human DNA from the long strand and then incorporate it into the
genome of a bacteria, or a bacterial virus. The fragment is then is
replicated within the bacterial cell many times and every time the
bacterial cell divides, the new cells also contain the introduced

D
DNA fragment. Bacterial cells reproduce prolifically, and so this
process ends up making millions of cells that all contain the
introduced DNA fragment, enough that researchers can study it in
detail and figure out the sequence of the base pairs.
With time, researchers have been able to study an ever greater
number of different DNA fragments, that is, different genes. It
became clear that certain variant DNA sequences were
associated with particular conditions: diseases such as cystic
fibrosis or breast cancer, or normal, non-harmful variants like red
hair. There was initially a lot of opposition to the Human Genome
Project, even from some scientists. Considering only around 1.5
per cent of our genome is actual genes that code for proteins, it
was thought that much of the $3 billion cost to sequence the
entire human genome would be wasted on the junk DNA that
scientists thought didnt get used. The important role the junk
DNA plays in gene regulation wasnt yet appreciated.

A cell in human body is simply invisible to naked

eye, Microscopes are essential to view them. A
Human DNA which is about 2m long gets packed so
well that it fits into cell nucleus, then think of the
difficulty in viewing a DNA

Research groups in many

countries, including
Australia, began to
sequence different genes,
providing the beginnings of
a total human gene map. In
1989, the Human Genome
Organization (HUGO) was
found by leading scientists
to coordinate the massive

International effort involved in collecting sequence data to unravel

the secrets of our genes.

HUMAN GENOME PROJECT

The Human Genome Project aimed to map the entire genome, including
the position of every human gene along the DNA strand, and then to
determine the sequence of each genes base pairs. At the time, sequencing
even a small gene could take months, so this was seen as a stupendous
and very costly undertaking. Fortunately, biotechnology was advancing
rapidly, and by the time the project was finishing it was possible to
sequence the DNA of a gene in a few hours. Even so, the project took ten
years to complete; the first draft of the human genome was announced in
June 2000.
In February 2001, the publicly funded Human Genome Project and the
private company Celera both announced that they had mapped virtually all
of the human genome, and had begun the task of working out the functions
of the many new genes that were identified. Scientists were surprised to
find that humans only have around 25,000 genes, not much more than the
roundworm Caenorhabditis elegans, and less than a tiny water crustacean
called Daphnia, which has around 30,000. However, genome sequencing
was making it clear that an organism's complexity is not necessarily related
to its number of genes.

Human genes categorized by function of the transcribed proteins, given both as

number of encoding genes and percentage of all genes.

Also, while we might have a surprisingly small number of genes, they are
often expressed in multiple and complex ways. Numerous genes have as
many as a dozen different functions and may be translated into several
different versions active in different tissues. We also have a lot of extra
DNA that doesnt make up specific genes. So even though the puffer
fishTetraodon nigroviridis has more genes than we donearly 28,000the
size of its entire genome is actually only around one tenth of ours as it has
much less of the non-coding DNA.
In April 2003, the 50th anniversary of the publication of the structure of
DNA, the complete final map of the Human Genome was announced. The
DNA from a large number of donors, women and men from different
nations and of different races, contributed to this typical Human Genome
Sequence.
The process of identifying
the boundaries between
genes and other features
in a raw DNA sequence is
called genome
annotation and is in the
domain of bioinformatics.
While expert biologists
make the best annotators,
their work proceeds slowly,
and computer programs
are increasingly used to
meet the high-throughput
demands of genome
sequencing projects.
Beginning in 2008, a new
technology known as RNAseq was

The first printout of the human genome to be presented as a

series of books, displayed at the Wellcome Collection,
London

Introduced that allowed scientists to directly sequence the messenger RNA

in cells. This replaced previous methods of annotation, which relied on
inherent properties of the DNA sequence, with direct measurement, which
was much more accurate. Today, annotation of the human genome and
other genomes relies primarily on deep sequencing of the transcripts in
every human tissue using RNA-seq. These experiments have revealed that
over 90% of genes contain at least one and usually several alternative

S
splice variants, in which the exons are combined in different ways to
produce 2 or more gene products from the same locus.
The genome published by the HGP does not represent the sequence of
every individual's genome. It is the combined mosaic of a small number of
anonymous donors, all of European origin. The HGP genome is a scaffold
for future work in identifying differences among individuals. Subsequent
projects sequenced the genomes of multiple distinct ethnic groups, though
as of today there is still only one "reference genome.

FINDINGS
Key findings of the draft (2001) and complete (2004) genome sequences
include:
1. There are approximately 22,300 protein-coding genes in human
beings, the same range as in other mammals.
2. The human genome has significantly more segmental
duplications (nearly identical, repeated sections of DNA) than had
been previously suspected. At the time when the draft sequence was
published fewer than 7% of protein families appeared to be
vertebrate specific.

ACCOMPLISHMENT
The Human Genome Project was started in 1990 with the goal of
sequencing and identifying all three billion chemical units in the human
genetic instruction set, finding the genetic roots of disease and then
developing treatments. It is considered a Mega Project because the human
genome has approximately 3.3 billion base-pairs. With the sequence in
hand, the next step was to identify the genetic variants that increase the
risk for common diseases like cancer and diabetes.
It was far too expensive at that time to think of sequencing patients whole
genomes. So the National Institutes of Health embraced the idea for a
"shortcut", which was to look just at sites on the genome where many
people have a variant DNA unit. The theory behind the shortcut was that,
since the major diseases are common, so too would be the genetic variants
that caused them. Natural selection keeps the human genome free of
variants that damage health before children are grown, the theory held, but
fails against variants that strike later in life, allowing them to become quite

Common. (In 2002 the National Institutes of Health started a $138 million
dollar project called the Hap Map to catalog the common variants in
European, East Asian and African genomes.)

A, For each Tetraodon chromosome, coloured segments

represent conserved synteny with a particular human
chromosome. Synteny is defined as groups of two or
more Tetraodon genes that possess an orthologue on the same
human chromosome, irrespective of orientation or
order. Tetraodon chromosomes are not in descending order by
size because of unequal sequence coverage. The entire map
includes 5,518 orthologues in 900 syntenic segments. B, On
the human genome the map is composed of 905 syntenic
segments. See Supplementary Information for the synteny map
between Tetraodon and mouse

The genome was broken

into smaller pieces;
approximately 150,000 base
pairs in length. These
pieces were then ligated
into a type of vector known
as "bacterial artificial
chromosomes", or BACs,
which are derived from
bacterial chromosomes
which have been genetically
engineered. The vectors
containing the genes can be
inserted into bacteria where
they are copied by the
bacterial DNA
replication machinery. Each
of these pieces was then
sequenced separately as a
small "shotgun" project and
then assembled. The larger,
150,000 base pairs go
together to create
chromosomes. This is
known as the "hierarchical
shotgun" approach,
because the genome is first
broken into relatively large
chunks, which are then
mapped to chromosomes
before being selected for
sequencing. Funding came
from the US government
through the National
Institutes of Health in the
United States, and a UK
charity organization,
the Wellcome Trust, as well
as numerous other groups
from around the world.

ETHICAL, LEGAL & SOCIAL

ISSUES
At the onset of the Human Genome Project several ethical, legal, and
social concerns were raised in regards to how increased knowledge of the
human genome could be used to discriminate against people. One of the
main concerns of most individuals was the fear that both employers and
health insurance companies would refuse to hire individuals or refuse to
provide insurance to people because of a health concern indicated by
someone's genes. In 1996 the United States passed the Health Insurance
Portability and Accountability Act (HIPAA) which protects against the
unauthorized and non-consensual release of individually identifiable health
information to any entity not actively engaged in the provision of healthcare
services to a patient.
Along with identifying all of the
approximately 20,00025,000 genes in the
human genome, the Human Genome
Project also sought to address the ethical,
legal, and social issues that were created
by the onset of the project. For that the
Ethical, Legal, and Social Implications
(ELSI) program was founded in 1990. Five
percent of the annual budget was allocated
to address the ELSI arising from the
project. This budget started at
approximately $1.57 million in the year
1990, but increased to approximately $18
million in the year 2014.
Whilst the project may offer significant benefits to medicine and scientific
research, some authors have emphasized the need to address the
potential social consequences of mapping the human genome.
"Molecularising disease and their possible cure will have a profound impact
on what patients expect from medical help and the new generation of
doctors' perception of illness."

OBSERVATION
The project was not able to sequence all the DNA found in human cells. It
sequenced only "euchromatic" regions of the genome, which make up
more than 95% of the genome. The other regions, called
"heterochromatic" are found in centromeres and telomeres, and were not
sequenced under the project.
The Human Genome Project was declared complete in April 2003. An initial
rough draft of the human genome was available in June 2000 and by
February 2001 a working draft had been completed and published followed
by the final sequencing mapping of the human genome on April 14, 2003.
Although this was reported to cover 99% of the euchromatic human
genome with 99.99% accuracy, a major quality assessment of the human
genome sequence was published on May 27, 2004 indicating over 92% of
sampling exceeded 99.99% accuracy which was within the intended
goal. Further analyses and papers on the HGP continue to occur.

A researcher reviews a DNA

sequence.

CONCLUSION
There is no doubt that information from the Human Genome Project
provides huge benefits to human health in helping to understand and treat
genetic diseases (such as breast cancer, cystic fibrosis and sickle cell
anaemia). However, some people see ethical issues, and wonder if
scientists are playing God with our genomes.
Could genetic information be misused; for example, through genetic
discrimination by employers or insurance companies? Most people agree
that gene testing can be used ethically to prevent serious diseases such as
cancer, or during pregnancy to avoid the birth of someone with a severe
handicap, but should we allow gene testing to choose a child who will be
able to be better at sports, or more intelligent? What about sex selection,
already a problem in some countries? And will it become possible to use
genetic information to change genes in children or adults for the better? Do
we really want to know if we run the risk of developing a particular disease
that may or may not be treatable? What are the privacy issues regarding
genome screening on a population scale? Still many more such questions
arise and leave us in oblivion of deep thoughts, yet we need to believe in
science and its advancements and realize that with NEW KNOWLEDGE
COMES HUGE NEW RESPONSIBILITIES.