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 amount 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.

, 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 several alternative 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.
FINDING
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 appreared to be verbrate

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.

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 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.

CONCLUSIONS
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.
Bibliography:
clearly.com

http://www.ornl.gov/sic/
techresourses/Human_Geenome/
project/info.com

en.wikipedia.org/wiki/DNA
Books: