HUMAN

GENOME

SUBMITTED BY,

SAURAV KUMAR
. 5975

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 CERTIFICATE

Certified that this is a Bonafide Record of project work

done in biology

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ACKNOWLEDGEMENT
I would like to express my special thanks of gratitude to my
Biology teacher Mr.Mahadevan G Nair as well we Biology lab
Assistant Mr.Lal Abraham Thomas who gave me the golden
opportunities 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.

I ONCE AGAIN THANK EVERYBODY WHO HAS

HELPED ME IN ACCOMPLISHING MY JOB

Signature

contents
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  Introduction

 Why Study Our Genome?

 Human Genome Project

 Ethical, Legal and Social

Issus
 Observation

 Conclusion

 Reference

Introduction

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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:

 nitrogenous bases there are four of these: adenine (A),

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

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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

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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

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(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

Population with wide range of character

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 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 long strand and then incorporate it into the
genome of a bacteria, or a bacterial virus. The fragment is then

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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 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

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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.

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 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 gename
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.

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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 fish Tetraodon nigrovirdis 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

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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.
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

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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.

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

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 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 of free 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 Welcome
Trust, as well as numerous other groups from around the world.

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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 mast 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

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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
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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
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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.

REFERENCE
 HELP FROM INTERNET AND WIKIPEDIA

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 INFORMATION FROM LIBRARY
 HELP FROM TEACHERS
 COMPREHENSIVE LAB MANUAL MR.LAL ABRAHAM
THOMAS

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