CONTENTS

1 Introduction about HGP

2 Study Our Genome?

3 HGP

4 Ethical, Legal and Social Issues

5 Observation

6 Conclusion

Bibliography
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 don’t have a nucleus). DNA is a
long molecule, made up of lots of smaller units. To make a DNA molecule
you need:

1 nitrogenous bases—there are four of these: adenine (A), thymine (T),

cytosine (C), guanine (C)

2 carbon sugar molecules

3 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 DNA—the human genome. This amounts to a DNA
molecule about a metre long.
It’s the order in which the base pairs are arranged—their sequence—in
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 fish’s DNA is
different to those in a monkey.

The base pair sequence of all people is nearly identical—that’s what

makes us all humans. However, there are small differences in the order
of the three billion base pairs in everyone’s 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).

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.

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 Francis Collins, former director of the
National Human Genome Research Institute, led the Human Genome
Project.
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 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 didn’t get used. The important role the ‘junk’ DNA plays in
gene regulation wasn’t yet appreciated.

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 gene’s 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.
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 doesn’t make up specific genes. So even though the
puffer fishTetraodon nigroviridis has more genes than we do—nearly
28,000—the 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
RNA-seq was 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 severalalternative 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.) 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 20,000–25,000 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.
 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.