BIOLOGY

INVESTIGATORY
PROJECT

TOPIC : Human
Genome

NAME : VAISHNAVI.A
CLASS: XII
ROLL NO: 10611035
 ACKNOWLEDGEMNT

I would like to express my special

thanks of gratitude to my Biology
teacher Mrs. Uma Devi as well as our
Principal Mrs. Vasantha Raman 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 .
 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 (Deoxyribose Nucleic Acid )
is found in the nucleus of every cell
in our body ( apart from RBC’S which
don’t have a nucleus in them ) . DNA
is a long molecule , made up of lots
of smaller units .

To make DNA molecule you need :

 Nitrogenous bases :
There are four of these : Adenine
(A) , Thymine (T) , Cytosine (C) ,
Guanine (G) .
 Carbon sugar molecule
 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 base 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 a
human DNA-the human genome .
This amounts to a DNA moelcule
about a meter 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 pairs 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 color ,
 eye color , 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 23pairs 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 ABOUT
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
our body to cause a 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 1970’s
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 onto the
genome of a bacteria , or a
bacterial virus . The fragment is
then replicated within the
bacterial cell many times and
every time the bacterial cell
divides , the new cells also
contain the introduced DNA
fragments . 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
in detail and figure out the
sequence of the base pairs .
With time , researchers have been
able to study even greater
numbers 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% of our genomes is
actual genes that codes for
proteins , it was thought that
much of the $3billion cost to
sequence the entire human
genome would be wasted on the
‘junk’ DNA that scientists thought
didn’t get used . The important
role of the ‘junk’ DNA plays in
gene regulation wasn’t yet
appropriated .

Research groups in many

countries , many including ,
Australia , began to sequence to
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 structure .
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 a 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 10 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 many new genes that
were identified . Scientists were
surprised to find that humans
only have around 25,000 genes ,
not much more than
Caenorhabditis( round worm )
and less than a tiny water
Crustacean called Daphnia ,
which has around 30,000 .
However , genome sequencing was
making it clear than an
organism’s complexity is not
necessarily related to its number
of genes .
Human genes categorized by function of the transcribed
proteins , give 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
dozen different functions and
maybe 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 Tetraodon nigrovirdist( puffer
fish ) 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 different races , contributed
to the ‘typical’ Human Genome
Sequence .

The first printout of the human genome to be presented

as a series of books , displayed at the Wellcome
Collection , London .

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-throughout demands of
genome sequencing projects .
Beginning in 2008 , a new
technology known as RNA-
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
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 I
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 individuals 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 only on “ reference
genome “ .

FINDINGS

Key findings of the draft (2001)

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

ACCOMPLISHMENTS

The Human Genome Project was

started in 1900 with 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 as 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 patient’s
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 .

National selection keeps the human

genome free of variants of 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
Institute of Health started as $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 similar

pieces ; approximately 150,000 base
pairs in length . These pieces were
then ligated into a type of vector
known as “ bacterial artificial
chromosome “ , or BAC’s 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 .
 A : For each Tetraodon chromosome, colored segments
represent conserved synthon with a particular human
chromosome. Synthon 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 syntonic segments.
B : On the human genome the map is composed of905
syntonic segments. See Supplementary Information for the
syntonic map between Tetraodon and mouse .
 ETHICAL, LEGAL AND
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 doctor's perception of
illness."
 OBSERVATION

The project was not able to sequence

all the DNA found in human cells. It
sequenced only "achromatic" regions
of the genome, which make up more
than95% 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
achromatic 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 .