BIOLOGY PROJECT
ACKNOWLEDGEMENT
I would like to express my special thanks of gratitude to my Biology teacher
Mr. Rajdeep Mandal as well as our principal Mrs. Mala Sharma 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
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
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 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 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).
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 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
A cell in human body is simply invisible to naked eye,
Human Genome Organization
Microscopes are essential to view them. A Human DNA (HUGO) was found by leading
which is about 2m long gets packed so well that it fits
into cell nucleus, then think of the difficulty in viewing a scientists to coordinate the
DNA 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.
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 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. The first printout of the human genome to be presented as a
series of books, displayed at the Wellcome Collection, London
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
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
A, For each Tetraodon chromosome, coloured segments represent conserved chromosomes before being
synteny with a particular human chromosome. Synteny is defined as groups of
two or selected for sequencing.
more Tetraodon genes that possess an orthologue on the same human Funding came from the US
chromosome, irrespective of orientation or order. Tetraodon
chromosomes are not in descending order by size because of unequal
government through the
sequence coverage. The entire map includes 5,518 orthologues in 900 syntenic National Institutes of Health
segments. B, On the human genome the map is composed of 905 syntenic
in the United States, and a
segments. See Supplementary Information for the synteny map between
Tetraodon and mouse 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.
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.
